ID   UBP6_HUMAN              Reviewed;        1406 AA.
AC   P35125; B9A6N0; Q15634; Q86WP6; Q8IWT4;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   19-JUL-2004, sequence version 2.
DT   27-MAR-2024, entry version 188.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 6;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 6;
DE   AltName: Full=Proto-oncogene TRE-2;
DE   AltName: Full=RN-tre {ECO:0000303|PubMed:19077034};
DE   AltName: Full=Ubiquitin thioesterase 6;
DE   AltName: Full=Ubiquitin-specific-processing protease 6;
GN   Name=USP6; Synonyms=HRP1, TRE2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY, AND
RP   VARIANTS ARG-475 AND GLN-912.
RC   TISSUE=Ewing sarcoma;
RX   PubMed=1565468;
RA   Nakamura T., Hillova J., Mariage-Samson R., Onno M., Huebner K.,
RA   Cannizzaro L.A., Boghosian-Sell L., Croce C.M., Hill M.;
RT   "A novel transcriptional unit of the tre oncogene widely expressed in human
RT   cancer cells.";
RL   Oncogene 7:733-741(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE SPLICING,
RP   TISSUE SPECIFICITY, AND DISCUSSION OF TRE2 EVOLUTION.
RX   PubMed=12604796; DOI=10.1073/pnas.0437015100;
RA   Paulding C.A., Ruvolo M., Haber D.A.;
RT   "The Tre2 (USP6) oncogene is a hominoid-specific gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:2507-2511(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), VARIANT ARG-475, FUNCTION, AND
RP   SUBCELLULAR LOCATION.
RC   TISSUE=Brain;
RX   PubMed=19077034; DOI=10.1111/j.1365-2443.2008.01251.x;
RA   Ishibashi K., Kanno E., Itoh T., Fukuda M.;
RT   "Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC)
RT   protein that possesses Rab3A-GAP activity.";
RL   Genes Cells 14:41-52(2009).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16625196; DOI=10.1038/nature04689;
RA   Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA   Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA   Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA   Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA   DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA   Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA   Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA   LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA   Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA   Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA   Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA   Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA   Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT   "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT   human lineage.";
RL   Nature 440:1045-1049(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-475.
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   CHARACTERIZATION.
RX   PubMed=8247125; DOI=10.1038/366313a0;
RA   Papa F.R., Hochstrasser M.;
RT   "The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product
RT   of the human tre-2 oncogene.";
RL   Nature 366:313-319(1993).
RN   [7]
RP   MUTAGENESIS OF THR-150 AND ARG-187.
RX   PubMed=14521938; DOI=10.1016/j.bbrc.2003.09.051;
RA   Bizimungu C., De Neve N., Burny A., Bach S., Bontemps F., Portetelle D.,
RA   Vandenbol M.;
RT   "Expression in a RabGAP yeast mutant of two human homologues, one of which
RT   is an oncogene.";
RL   Biochem. Biophys. Res. Commun. 310:498-504(2003).
RN   [8]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH RAC1 AND CDC42.
RX   PubMed=12612085; DOI=10.1128/mcb.23.6.2151-2161.2003;
RA   Masuda-Robens J.M., Kutney S.N., Qi H., Chou M.M.;
RT   "The TRE17 oncogene encodes a component of a novel effector pathway for Rho
RT   GTPases Cdc42 and Rac1 and stimulates actin remodeling.";
RL   Mol. Cell. Biol. 23:2151-2161(2003).
RN   [9]
RP   CHROMOSOMAL TRANSLOCATION WITH CDH11.
RX   PubMed=15026324; DOI=10.1158/0008-5472.can-03-2827;
RA   Oliveira A.M., Hsi B.L., Weremowicz S., Rosenberg A.E., Dal Cin P.,
RA   Joseph N., Bridge J.A., Perez-Atayde A.R., Fletcher J.A.;
RT   "USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst.";
RL   Cancer Res. 64:1920-1923(2004).
RN   [10]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARF6.
RX   PubMed=15509780; DOI=10.1128/mcb.24.22.9752-9762.2004;
RA   Martinu L., Masuda-Robens J.M., Robertson S.E., Santy L.C., Casanova J.E.,
RA   Chou M.M.;
RT   "The TBC (Tre-2/Bub2/Cdc16) domain protein TRE17 regulates plasma membrane-
RT   endosomal trafficking through activation of Arf6.";
RL   Mol. Cell. Biol. 24:9752-9762(2004).
RN   [11]
RP   FUNCTION, INTERACTION WITH CALMODULIN, UBIQUITINATION, AND MUTAGENESIS OF
RP   CYS-541.
RX   PubMed=16127172; DOI=10.1074/jbc.m505220200;
RA   Shen C., Ye Y., Robertson S.E., Lau A.W., Mak D.O., Chou M.M.;
RT   "Calcium/calmodulin regulates ubiquitination of the ubiquitin-specific
RT   protease TRE17/USP6.";
RL   J. Biol. Chem. 280:35967-35973(2005).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [13]
RP   FUNCTION.
RX   PubMed=20418905; DOI=10.1038/onc.2010.116;
RA   Ye Y., Pringle L.M., Lau A.W., Riquelme D.N., Wang H., Jiang T., Lev D.,
RA   Welman A., Blobel G.A., Oliveira A.M., Chou M.M.;
RT   "TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix
RT   metalloproteinase production via activation of NF-kappaB.";
RL   Oncogene 29:3619-3629(2010).
CC   -!- FUNCTION: Deubiquitinase with an ATP-independent isopeptidase activity,
CC       cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own
CC       deubiquitination. In vitro, isoform 2, but not isoform 3, shows
CC       deubiquitinating activity. Promotes plasma membrane localization of
CC       ARF6 and selectively regulates ARF6-dependent endocytic protein
CC       trafficking. Is able to initiate tumorigenesis by inducing the
CC       production of matrix metalloproteinases following NF-kappa-B
CC       activation. May act as a GTPase-activating protein for RAB3A
CC       (PubMed:19077034). {ECO:0000269|PubMed:15509780,
CC       ECO:0000269|PubMed:16127172, ECO:0000269|PubMed:19077034,
CC       ECO:0000269|PubMed:20418905}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC         and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC         residue protein attached to proteins as an intracellular targeting
CC         signal).; EC=3.4.19.12;
CC   -!- SUBUNIT: Interacts with RAC1 and CDC42. Interacts (via Rab-GAP TBC
CC       domain) with ARF6. Interacts with calmodulin (CALM1, CALM2 and/or
CC       CALM3); the interaction is calcium-dependent.
CC       {ECO:0000269|PubMed:12612085, ECO:0000269|PubMed:15509780,
CC       ECO:0000269|PubMed:16127172}.
CC   -!- INTERACTION:
CC       P35125-3; Q8N8A2: ANKRD44; NbExp=4; IntAct=EBI-954590, EBI-1245329;
CC       P35125-3; P10916: MYL2; NbExp=5; IntAct=EBI-954590, EBI-725770;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19077034}.
CC       Cytoplasm. Endosome. Note=Localizes to the plasma membrane and to
CC       filamentous structures within the cell corresponding to ARF6 regulated
CC       tubular endosomes. Activation of RAC1 and CDC42 can direct the
CC       relocalization of USP6 to the plasma membrane in a manner that depends
CC       on the integrity of the actin cytoskeleton.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P35125-1; Sequence=Displayed;
CC       Name=2; Synonyms=213(ORF2);
CC         IsoId=P35125-2; Sequence=VSP_010878, VSP_010879;
CC       Name=3; Synonyms=210(ORF1), oncTre210p;
CC         IsoId=P35125-3; Sequence=VSP_010880, VSP_010881;
CC   -!- TISSUE SPECIFICITY: Testis specific. Expressed in various cancer cell
CC       lines. {ECO:0000269|PubMed:12604796, ECO:0000269|PubMed:1565468}.
CC   -!- DOMAIN: The Rab-GAP TBC domain lacks GTPase activator activity but is
CC       necessary for interaction with ARF6.
CC   -!- PTM: Monubiquitinated; ubiquitination is calmodulin and calcium
CC       dependent. {ECO:0000269|PubMed:16127172}.
CC   -!- DISEASE: Note=A chromosomal aberration involving USP6 is a common
CC       genetic feature of aneurysmal bone cyst, a benign osseous neoplasm.
CC       Translocation t(16;17)(q22;p13) with CDH11. The translocation generates
CC       a fusion gene in which the strong CDH11 promoter is fused to the entire
CC       USP6 coding sequence, resulting in USP6 transcriptional up-regulation
CC       (PubMed:15026324). {ECO:0000269|PubMed:15026324}.
CC   -!- MISCELLANEOUS: The USP6 gene only exists in the primate lineage.
CC   -!- MISCELLANEOUS: [Isoform 3]: Was shown to be tumorigenic in transfected
CC       mice and seems not to act as GTPase activating protein. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/530/USP6";
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DR   EMBL; X63546; CAA45108.1; -; mRNA.
DR   EMBL; X63547; CAA45111.1; -; mRNA.
DR   EMBL; AY143550; AAN38838.1; -; mRNA.
DR   EMBL; AY163314; AAO21348.1; -; Genomic_DNA.
DR   EMBL; AB449915; BAH16658.1; -; mRNA.
DR   EMBL; AC012146; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471108; EAW90354.1; -; Genomic_DNA.
DR   CCDS; CCDS11069.2; -. [P35125-1]
DR   PIR; S57867; S57867.
DR   PIR; S57868; S22158.
DR   PIR; S57874; S22155.
DR   RefSeq; NP_001291213.1; NM_001304284.1. [P35125-1]
DR   RefSeq; NP_004496.2; NM_004505.3. [P35125-1]
DR   RefSeq; XP_011522352.1; XM_011524050.1. [P35125-1]
DR   RefSeq; XP_011522353.1; XM_011524051.2. [P35125-1]
DR   RefSeq; XP_011522354.1; XM_011524052.2. [P35125-1]
DR   RefSeq; XP_011522355.1; XM_011524053.2. [P35125-1]
DR   RefSeq; XP_011522356.1; XM_011524054.2. [P35125-1]
DR   RefSeq; XP_011522357.1; XM_011524055.2. [P35125-1]
DR   RefSeq; XP_011522358.1; XM_011524056.2. [P35125-1]
DR   RefSeq; XP_011522361.1; XM_011524059.2. [P35125-3]
DR   RefSeq; XP_016880779.1; XM_017025290.1.
DR   AlphaFoldDB; P35125; -.
DR   SMR; P35125; -.
DR   BioGRID; 114552; 26.
DR   IntAct; P35125; 6.
DR   STRING; 9606.ENSP00000460380; -.
DR   BindingDB; P35125; -.
DR   ChEMBL; CHEMBL4630817; -.
DR   MEROPS; C19.009; -.
DR   MEROPS; C19.044; -.
DR   iPTMnet; P35125; -.
DR   PhosphoSitePlus; P35125; -.
DR   BioMuta; USP6; -.
DR   DMDM; 50403738; -.
DR   EPD; P35125; -.
DR   jPOST; P35125; -.
DR   MassIVE; P35125; -.
DR   MaxQB; P35125; -.
DR   PaxDb; 9606-ENSP00000460380; -.
DR   PeptideAtlas; P35125; -.
DR   ProteomicsDB; 54980; -. [P35125-1]
DR   ProteomicsDB; 54981; -. [P35125-2]
DR   ProteomicsDB; 54982; -. [P35125-3]
DR   Antibodypedia; 11505; 236 antibodies from 29 providers.
DR   DNASU; 9098; -.
DR   Ensembl; ENST00000250066.6; ENSP00000250066.6; ENSG00000129204.17. [P35125-1]
DR   Ensembl; ENST00000572949.5; ENSP00000461581.1; ENSG00000129204.17. [P35125-3]
DR   Ensembl; ENST00000574788.6; ENSP00000460380.1; ENSG00000129204.17. [P35125-1]
DR   GeneID; 9098; -.
DR   KEGG; hsa:9098; -.
DR   MANE-Select; ENST00000574788.6; ENSP00000460380.1; NM_001304284.2; NP_001291213.1.
DR   UCSC; uc002gau.2; human. [P35125-1]
DR   AGR; HGNC:12629; -.
DR   CTD; 9098; -.
DR   DisGeNET; 9098; -.
DR   GeneCards; USP6; -.
DR   HGNC; HGNC:12629; USP6.
DR   HPA; ENSG00000129204; Group enriched (skeletal muscle, testis).
DR   MalaCards; USP6; -.
DR   MIM; 604334; gene.
DR   neXtProt; NX_P35125; -.
DR   OpenTargets; ENSG00000129204; -.
DR   Orphanet; 477742; Nodular fasciitis.
DR   PharmGKB; PA37254; -.
DR   VEuPathDB; HostDB:ENSG00000129204; -.
DR   eggNOG; KOG1102; Eukaryota.
DR   eggNOG; KOG1870; Eukaryota.
DR   GeneTree; ENSGT00940000155797; -.
DR   HOGENOM; CLU_005123_0_0_1; -.
DR   InParanoid; P35125; -.
DR   OrthoDB; 4687814at2759; -.
DR   PhylomeDB; P35125; -.
DR   TreeFam; TF324190; -.
DR   PathwayCommons; P35125; -.
DR   SignaLink; P35125; -.
DR   SIGNOR; P35125; -.
DR   BioGRID-ORCS; 9098; 17 hits in 1152 CRISPR screens.
DR   ChiTaRS; USP6; human.
DR   GeneWiki; USP6; -.
DR   GenomeRNAi; 9098; -.
DR   Pharos; P35125; Tbio.
DR   PRO; PR:P35125; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P35125; Protein.
DR   Bgee; ENSG00000129204; Expressed in Brodmann (1909) area 23 and 199 other cell types or tissues.
DR   ExpressionAtlas; P35125; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR   GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR   GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:UniProtKB.
DR   GO; GO:0003676; F:nucleic acid binding; TAS:ProtInc.
DR   GO; GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
DR   GO; GO:0036211; P:protein modification process; NAS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0060627; P:regulation of vesicle-mediated transport; IDA:UniProtKB.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 3.
DR   Gene3D; 1.10.8.270; putative rabgap domain of human tbc1 domain family member 14 like domains; 1.
DR   Gene3D; 1.10.10.750; Ypt/Rab-GAP domain of gyp1p, domain 1; 1.
DR   Gene3D; 1.10.472.80; Ypt/Rab-GAP domain of gyp1p, domain 3; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR000195; Rab-GAP-TBC_dom.
DR   InterPro; IPR035969; Rab-GAP_TBC_sf.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR21646:SF96; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 6; 1.
DR   Pfam; PF00566; RabGAP-TBC; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SMART; SM00164; TBC; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF47923; Ypt/Rab-GAP domain of gyp1p; 2.
DR   PROSITE; PS50086; TBC_RABGAP; 1.
DR   PROSITE; PS00972; USP_1; 1.
DR   PROSITE; PS00973; USP_2; 1.
DR   PROSITE; PS50235; USP_3; 1.
DR   Genevisible; P35125; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Calmodulin-binding; Cell membrane;
KW   Chromosomal rearrangement; Cytoplasm; Endosome; Hydrolase; Membrane;
KW   Protease; Proto-oncogene; Reference proteome; Thiol protease;
KW   Ubl conjugation; Ubl conjugation pathway.
FT   CHAIN           1..1406
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 6"
FT                   /id="PRO_0000080625"
FT   DOMAIN          100..292
FT                   /note="Rab-GAP TBC"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00163"
FT   DOMAIN          532..1369
FT                   /note="USP"
FT   REGION          348..380
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1120..1231
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1384..1406
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1132..1148
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1152..1201
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1213..1228
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1385..1400
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        541
FT                   /note="Nucleophile"
FT   ACT_SITE        1328
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   VAR_SEQ         1..317
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:1565468"
FT                   /id="VSP_010878"
FT   VAR_SEQ         318..359
FT                   /note="GLWARLRNQFFDTWAMNDDTVLKHLRASTKKLTRKQGDLPPP -> MPQRLP
FT                   HARQHTPLPLGSADYRRVVSVRPQGPHRDPKDSRDA (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:1565468"
FT                   /id="VSP_010879"
FT   VAR_SEQ         774..786
FT                   /note="NFPQDNQKVQLSV -> ISPLHHLQMECSP (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:1565468"
FT                   /id="VSP_010880"
FT   VAR_SEQ         787..1406
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:1565468"
FT                   /id="VSP_010881"
FT   VARIANT         475
FT                   /note="W -> R (in dbSNP:rs8073787)"
FT                   /evidence="ECO:0000269|PubMed:1565468,
FT                   ECO:0000269|PubMed:19077034, ECO:0000269|Ref.5"
FT                   /id="VAR_051522"
FT   VARIANT         525
FT                   /note="V -> I (in dbSNP:rs2304449)"
FT                   /id="VAR_059749"
FT   VARIANT         912
FT                   /note="R -> Q (in dbSNP:rs9899177)"
FT                   /evidence="ECO:0000269|PubMed:1565468"
FT                   /id="VAR_051523"
FT   MUTAGEN         150
FT                   /note="T->R: Does not restore GAP activity in yeast
FT                   complementation assay."
FT                   /evidence="ECO:0000269|PubMed:14521938"
FT   MUTAGEN         187
FT                   /note="R->Q: Does not restore GAP activity in yeast
FT                   complementation assay."
FT                   /evidence="ECO:0000269|PubMed:14521938"
FT   MUTAGEN         541
FT                   /note="C->S: Loss of enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:16127172"
FT   CONFLICT        963
FT                   /note="N -> I (in Ref. 1; CAA45111)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1406 AA;  158658 MW;  D3A6822CEB441DB3 CRC64;
     MDMVENADSL QAQERKDILM KYDKGHRAGL PEDKGPEPVG INSSIDRFGI LHETELPPVT
     AREAKKIRRE MTRTSKWMEM LGEWETYKHS SKLIDRVYKG IPMNIRGPVW SVLLNIQEIK
     LKNPGRYQIM KERGKRSSEH IHHIDLDVRT TLRNHVFFRD RYGAKQRELF YILLAYSEYN
     PEVGYCRDLS HITALFLLYL PEEDAFWALV QLLASERHSL PGFHSPNGGT VQGLQDQQEH
     VVPKSQPKTM WHQDKEGLCG QCASLGCLLR NLIDGISLGL TLRLWDVYLV EGEQVLMPIT
     SIALKVQQKR LMKTSRCGLW ARLRNQFFDT WAMNDDTVLK HLRASTKKLT RKQGDLPPPA
     KREQGSLAPR PVPASRGGKT LCKGYRQAPP GPPAQFQRPI CSASPPWASR FSTPCPGGAV
     REDTYPVGTQ GVPSLALAQG GPQGSWRFLE WKSMPRLPTD LDIGGPWFPH YDFEWSCWVR
     AISQEDQLAT CWQAEHCGEV HNKDMSWPEE MSFTANSSKI DRQKVPTEKG ATGLSNLGNT
     CFMNSSIQCV SNTQPLTQYF ISGRHLYELN RTNPIGMKGH MAKCYGDLVQ ELWSGTQKSV
     APLKLRRTIA KYAPKFDGFQ QQDSQELLAF LLDGLHEDLN RVHEKPYVEL KDSDGRPDWE
     VAAEAWDNHL RRNRSIIVDL FHGQLRSQVK CKTCGHISVR FDPFNFLSLP LPMDSYMDLE
     ITVIKLDGTT PVRYGLRLNM DEKYTGLKKQ LRDLCGLNSE QILLAEVHDS NIKNFPQDNQ
     KVQLSVSGFL CAFEIPVPSS PISASSPTQI DFSSSPSTNG MFTLTTNGDL PKPIFIPNGM
     PNTVVPCGTE KNFTNGMVNG HMPSLPDSPF TGYIIAVHRK MMRTELYFLS PQENRPSLFG
     MPLIVPCTVH TRKKDLYDAV WIQVSWLARP LPPQEASIHA QDRDNCMGYQ YPFTLRVVQK
     DGNSCAWCPQ YRFCRGCKID CGEDRAFIGN AYIAVDWHPT ALHLRYQTSQ ERVVDKHESV
     EQSRRAQAEP INLDSCLRAF TSEEELGESE MYYCSKCKTH CLATKKLDLW RLPPFLIIHL
     KRFQFVNDQW IKSQKIVRFL RESFDPSAFL VPRDPALCQH KPLTPQGDEL SKPRILAREV
     KKVDAQSSAG KEDMLLSKSP SSLSANISSS PKGSPSSSRK SGTSCPSSKN SSPNSSPRTL
     GRSKGRLRLP QIGSKNKPSS SKKNLDASKE NGAGQICELA DALSRGHMRG GSQPELVTPQ
     DHEVALANGF LYEHEACGNG CGDGYSNGQL GNHSEEDSTD DQREDTHIKP IYNLYAISCH
     SGILSGGHYI TYAKNPNCKW YCYNDSSCEE LHPDEIDTDS AYILFYEQQG IDYAQFLPKI
     DGKKMADTSS TDEDSESDYE KYSMLQ
//