UBP13_HUMAN
ID UBP13_HUMAN Reviewed; 863 AA.
AC Q92995; A8K2S3; B4DYF3; D3DNS2; Q96B25;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 13;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 13;
DE AltName: Full=Isopeptidase T-3;
DE Short=ISOT-3;
DE AltName: Full=Ubiquitin thioesterase 13;
DE AltName: Full=Ubiquitin-specific-processing protease 13;
GN Name=USP13; Synonyms=ISOT3;
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] (ISOFORM 1).
RX PubMed=9841226; DOI=10.1016/s0378-1119(98)00341-2;
RA Timms K.M., Ansari-Lari M.A., Morris W., Brown S.N., Gibbs R.A.;
RT "The genomic organization of Isopeptidase T-3 (ISOT-3), a new member of the
RT ubiquitin specific protease family (UBP).";
RL Gene 217:101-106(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION.
RX PubMed=17653289; DOI=10.1371/journal.pone.0000679;
RA Catic A., Fiebiger E., Korbel G.A., Blom D., Galardy P.J., Ploegh H.L.;
RT "Screen for ISG15-crossreactive deubiquitinases.";
RL PLoS ONE 2:E679-E679(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-122, AND IDENTIFICATION BY
RP 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114 AND THR-122, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=21962518; DOI=10.1016/j.cell.2011.08.037;
RA Liu J., Xia H., Kim M., Xu L., Li Y., Zhang L., Cai Y., Norberg H.V.,
RA Zhang T., Furuya T., Jin M., Zhu Z., Wang H., Yu J., Li Y., Hao Y.,
RA Choi A., Ke H., Ma D., Yuan J.;
RT "Beclin1 controls the levels of p53 by regulating the deubiquitination
RT activity of USP10 and USP13.";
RL Cell 147:223-234(2011).
RN [11]
RP FUNCTION, INTERACTION WITH SIAH2, AND MUTAGENESIS OF TRP-221; LYS-233;
RP PHE-273; CYS-345; MET-664; MET-739; HIS-814 AND HIS-823.
RX PubMed=21659512; DOI=10.1074/jbc.m111.218214;
RA Scortegagna M., Subtil T., Qi J., Kim H., Zhao W., Gu W., Kluger H.,
RA Ronai Z.A.;
RT "USP13 enzyme regulates Siah2 ligase stability and activity via
RT noncatalytic ubiquitin-binding domains.";
RL J. Biol. Chem. 286:27333-27341(2011).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF CYS-345.
RX PubMed=21811243; DOI=10.1038/ncomms1421;
RA Zhao X., Fiske B., Kawakami A., Li J., Fisher D.E.;
RT "Regulation of MITF stability by the USP13 deubiquitinase.";
RL Nat. Commun. 2:414-414(2011).
RN [13]
RP FUNCTION, AND INTERACTION WITH UFD1.
RX PubMed=21571647; DOI=10.1073/pnas.1100028108;
RA Chen M., Gutierrez G.J., Ronai Z.A.;
RT "Ubiquitin-recognition protein Ufd1 couples the endoplasmic reticulum (ER)
RT stress response to cell cycle control.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:9119-9124(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-122, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP FUNCTION, AND INTERACTION WITH AMFR; BAG6 AND UBL4A.
RX PubMed=24424410; DOI=10.7554/elife.01369;
RA Liu Y., Soetandyo N., Lee J.G., Liu L., Xu Y., Clemons W.M. Jr., Ye Y.;
RT "USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-
RT associated degradation.";
RL Elife 3:E01369-E01369(2014).
RN [16]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-311 AND LYS-405, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [17]
RP STRUCTURE BY NMR OF 188-301 AND 652-777, FUNCTION, DOMAIN, AND
RP UBIQUITIN-BINDING.
RX PubMed=22216260; DOI=10.1371/journal.pone.0029362;
RA Zhang Y.H., Zhou C.J., Zhou Z.R., Song A.X., Hu H.Y.;
RT "Domain analysis reveals that a deubiquitinating enzyme USP13 performs non-
RT activating catalysis for Lys63-linked polyubiquitin.";
RL PLoS ONE 6:E29362-E29362(2011).
CC -!- FUNCTION: Deubiquitinase that mediates deubiquitination of target
CC proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various
CC processes such as autophagy and endoplasmic reticulum-associated
CC degradation (ERAD). Component of a regulatory loop that controls
CC autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a
CC key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-
CC containing complexes. Also deubiquitinates USP10, an essential
CC regulator of p53/TP53 stability. In turn, PIK3C3/VPS34-containing
CC complexes regulate USP13 stability, suggesting the existence of a
CC regulatory system by which PIK3C3/VPS34-containing complexes regulate
CC p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1
CC and mediates deubiquitination of SKP2, thereby regulating endoplasmic
CC reticulum-associated degradation (ERAD). Also regulates ERAD through
CC the deubiquitination of UBL4A a component of the BAG6/BAT3 complex.
CC Mediates stabilization of SIAH2 independently of deubiquitinase
CC activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2
CC autoubiquitination. Has a weak deubiquitinase activity in vitro and
CC preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In
CC contrast to USP5, it is not able to mediate unanchored polyubiquitin
CC disassembly. Able to cleave ISG15 in vitro; however, additional
CC experiments are required to confirm such data.
CC {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647,
CC ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243,
CC ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260,
CC ECO:0000269|PubMed:24424410}.
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 -!- ACTIVITY REGULATION: Specifically inhibited by spautin-1 (specific and
CC potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP13
CC and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-
CC containing complexes. The weak deubiquitinase activity in vitro
CC suggests the existence of some mechanism that activates the enzyme.
CC {ECO:0000269|PubMed:21962518}.
CC -!- SUBUNIT: Interacts with UFD1. Interacts (via UBA domains) with SIAH2
CC (when ubiquitinated). Interacts with BAG6; the interaction is direct
CC and may mediate UBL4A deubiquitination (PubMed:24424410). Interacts
CC (via UBA 2 domain) with AMFR; the interaction is direct
CC (PubMed:24424410). Interacts with UBL4A; may be indirect via BAG6
CC (PubMed:24424410). {ECO:0000269|PubMed:21571647,
CC ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:24424410}.
CC -!- INTERACTION:
CC Q92995; P54252: ATXN3; NbExp=3; IntAct=EBI-714351, EBI-946046;
CC Q92995; Q15038: DAZAP2; NbExp=3; IntAct=EBI-714351, EBI-724310;
CC Q92995; Q13148: TARDBP; NbExp=3; IntAct=EBI-714351, EBI-372899;
CC Q92995; Q9BYV6: TRIM55; NbExp=2; IntAct=EBI-714351, EBI-2341179;
CC Q92995; Q969Q1: TRIM63; NbExp=2; IntAct=EBI-714351, EBI-5661333;
CC Q92995; PRO_0000449630 [P0DTD1]: rep; Xeno; NbExp=4; IntAct=EBI-714351, EBI-25475888;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92995-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92995-2; Sequence=VSP_043954;
CC -!- TISSUE SPECIFICITY: Highly expressed in ovary and testes.
CC -!- DOMAIN: The UBP-type zinc finger has lost its ability to bind ubiquitin
CC and USP13 is not activated by unanchored ubiquitin. Swapping with the
CC UBP-type zinc finger from USP5 restores ability to bind unanchored
CC ubiquitin and subsequent activation of the protein (PubMed:22216260).
CC {ECO:0000269|PubMed:22216260}.
CC -!- DOMAIN: The UBA domains mediate binding to ubiquitin.
CC {ECO:0000269|PubMed:22216260}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U75362; AAC63405.1; -; mRNA.
DR EMBL; AK290338; BAF83027.1; -; mRNA.
DR EMBL; AK302404; BAG63715.1; -; mRNA.
DR EMBL; AC007687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125604; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78383.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78384.1; -; Genomic_DNA.
DR EMBL; BC016146; AAH16146.1; -; mRNA.
DR CCDS; CCDS3235.1; -. [Q92995-1]
DR RefSeq; NP_003931.2; NM_003940.2. [Q92995-1]
DR PDB; 2L80; NMR; -; A=188-301.
DR PDB; 2LBC; NMR; -; A=652-777.
DR PDBsum; 2L80; -.
DR PDBsum; 2LBC; -.
DR AlphaFoldDB; Q92995; -.
DR BMRB; Q92995; -.
DR SMR; Q92995; -.
DR BioGRID; 114465; 96.
DR DIP; DIP-53511N; -.
DR IntAct; Q92995; 45.
DR MINT; Q92995; -.
DR STRING; 9606.ENSP00000263966; -.
DR BindingDB; Q92995; -.
DR ChEMBL; CHEMBL3407324; -.
DR MEROPS; C19.012; -.
DR GlyGen; Q92995; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92995; -.
DR PhosphoSitePlus; Q92995; -.
DR BioMuta; USP13; -.
DR DMDM; 209572692; -.
DR EPD; Q92995; -.
DR jPOST; Q92995; -.
DR MassIVE; Q92995; -.
DR MaxQB; Q92995; -.
DR PaxDb; Q92995; -.
DR PeptideAtlas; Q92995; -.
DR PRIDE; Q92995; -.
DR ProteomicsDB; 75664; -. [Q92995-1]
DR ProteomicsDB; 75665; -. [Q92995-2]
DR Antibodypedia; 1352; 321 antibodies from 35 providers.
DR DNASU; 8975; -.
DR Ensembl; ENST00000263966.8; ENSP00000263966.3; ENSG00000058056.10. [Q92995-1]
DR Ensembl; ENST00000496897.5; ENSP00000417146.1; ENSG00000058056.10. [Q92995-2]
DR GeneID; 8975; -.
DR KEGG; hsa:8975; -.
DR MANE-Select; ENST00000263966.8; ENSP00000263966.3; NM_003940.3; NP_003931.2.
DR UCSC; uc003fkh.4; human. [Q92995-1]
DR CTD; 8975; -.
DR DisGeNET; 8975; -.
DR GeneCards; USP13; -.
DR HGNC; HGNC:12611; USP13.
DR HPA; ENSG00000058056; Tissue enhanced (skeletal muscle, tongue).
DR MIM; 603591; gene.
DR neXtProt; NX_Q92995; -.
DR OpenTargets; ENSG00000058056; -.
DR PharmGKB; PA37237; -.
DR VEuPathDB; HostDB:ENSG00000058056; -.
DR eggNOG; KOG0944; Eukaryota.
DR GeneTree; ENSGT00940000157401; -.
DR HOGENOM; CLU_009884_1_0_1; -.
DR InParanoid; Q92995; -.
DR OMA; TMDMENN; -.
DR PhylomeDB; Q92995; -.
DR TreeFam; TF300576; -.
DR PathwayCommons; Q92995; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8948751; Regulation of PTEN stability and activity.
DR SignaLink; Q92995; -.
DR SIGNOR; Q92995; -.
DR BioGRID-ORCS; 8975; 12 hits in 1121 CRISPR screens.
DR ChiTaRS; USP13; human.
DR GeneWiki; USP13; -.
DR GenomeRNAi; 8975; -.
DR Pharos; Q92995; Tchem.
DR PRO; PR:Q92995; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q92995; protein.
DR Bgee; ENSG00000058056; Expressed in skeletal muscle tissue of biceps brachii and 203 other tissues.
DR ExpressionAtlas; Q92995; baseline and differential.
DR Genevisible; Q92995; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:1904288; F:BAT3 complex binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
DR GO; GO:1990380; F:Lys48-specific deubiquitinase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070628; F:proteasome binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR GO; GO:1904378; P:maintenance of unfolded protein involved in ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030318; P:melanocyte differentiation; TAS:UniProtKB.
DR GO; GO:1904294; P:positive regulation of ERAD pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0016579; P:protein deubiquitination; IBA:GO_Central.
DR GO; GO:0035523; P:protein K29-linked deubiquitination; IDA:MGI.
DR GO; GO:0044313; P:protein K6-linked deubiquitination; IDA:MGI.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 2.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR016652; Ubiquitinyl_hydrolase.
DR InterPro; IPR041432; UBP13_Znf-UBP_var.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR Pfam; PF17807; zf-UBP_var; 1.
DR PIRSF; PIRSF016308; UBP; 1.
DR SMART; SM00165; UBA; 2.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50030; UBA; 2.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Autophagy; Hydrolase; Isopeptide bond;
KW Metal-binding; Phosphoprotein; Protease; Reference proteome; Repeat;
KW Thiol protease; Ubl conjugation; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..863
FT /note="Ubiquitin carboxyl-terminal hydrolase 13"
FT /id="PRO_0000080635"
FT DOMAIN 336..861
FT /note="USP"
FT DOMAIN 652..693
FT /note="UBA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 727..767
FT /note="UBA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 187..295
FT /note="UBP-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT ACT_SITE 345
FT /note="Nucleophile"
FT /evidence="ECO:0000305"
FT ACT_SITE 823
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 214
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 244
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 122
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692"
FT CROSSLNK 311
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 405
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..65
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_043954"
FT MUTAGEN 221
FT /note="W->A: Does not abolish ability to stabilize SIAH2."
FT /evidence="ECO:0000269|PubMed:21659512"
FT MUTAGEN 233
FT /note="K->A: Does not abolish ability to stabilize SIAH2."
FT /evidence="ECO:0000269|PubMed:21659512"
FT MUTAGEN 273
FT /note="F->A: Impairs ability to stabilize SIAH2."
FT /evidence="ECO:0000269|PubMed:21659512"
FT MUTAGEN 345
FT /note="C->A: Abolishes deubiquitinating activity. Does not
FT abolish ability to stabilize SIAH2. Does not abolish
FT ability to stabilize SIAH2; when associated with A-814 and
FT A-823."
FT /evidence="ECO:0000269|PubMed:21659512,
FT ECO:0000269|PubMed:21811243"
FT MUTAGEN 664
FT /note="M->E: Impairs ability to stabilize SIAH2. Abolishes
FT ability to stabilize SIAH2; when associated with E-739."
FT /evidence="ECO:0000269|PubMed:21659512"
FT MUTAGEN 739
FT /note="M->E: Impairs ability to stabilize SIAH2. Abolishes
FT ability to stabilize SIAH2; when associated with E-664."
FT /evidence="ECO:0000269|PubMed:21659512"
FT MUTAGEN 814
FT /note="H->A: Does not abolish ability to stabilize SIAH2;
FT when associated with A-345 and A-823."
FT /evidence="ECO:0000269|PubMed:21659512"
FT MUTAGEN 823
FT /note="H->A: Does not abolish ability to stabilize SIAH2;
FT when associated with A-345 and A-814."
FT /evidence="ECO:0000269|PubMed:21659512"
FT CONFLICT 96
FT /note="V -> A (in Ref. 1; AAC63405)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="I -> V (in Ref. 2; BAF83027)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="L -> F (in Ref. 2; BAF83027)"
FT /evidence="ECO:0000305"
FT CONFLICT 325
FT /note="T -> A (in Ref. 2; BAF83027)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="L -> P (in Ref. 2; BAF83027)"
FT /evidence="ECO:0000305"
FT TURN 191..194
FT /evidence="ECO:0007829|PDB:2L80"
FT STRAND 212..214
FT /evidence="ECO:0007829|PDB:2L80"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:2L80"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:2L80"
FT STRAND 229..231
FT /evidence="ECO:0007829|PDB:2L80"
FT HELIX 244..251
FT /evidence="ECO:0007829|PDB:2L80"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:2L80"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:2L80"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:2L80"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2L80"
FT HELIX 284..290
FT /evidence="ECO:0007829|PDB:2L80"
FT HELIX 296..299
FT /evidence="ECO:0007829|PDB:2L80"
FT HELIX 656..662
FT /evidence="ECO:0007829|PDB:2LBC"
FT HELIX 669..678
FT /evidence="ECO:0007829|PDB:2LBC"
FT HELIX 683..692
FT /evidence="ECO:0007829|PDB:2LBC"
FT HELIX 693..695
FT /evidence="ECO:0007829|PDB:2LBC"
FT STRAND 697..700
FT /evidence="ECO:0007829|PDB:2LBC"
FT STRAND 710..714
FT /evidence="ECO:0007829|PDB:2LBC"
FT HELIX 730..739
FT /evidence="ECO:0007829|PDB:2LBC"
FT HELIX 743..753
FT /evidence="ECO:0007829|PDB:2LBC"
FT HELIX 757..765
FT /evidence="ECO:0007829|PDB:2LBC"
SQ SEQUENCE 863 AA; 97327 MW; 988713ADF8C0B938 CRC64;
MQRRGALFGM PGGSGGRKMA AGDIGELLVP HMPTIRVPRS GDRVYKNECA FSYDSPNSEG
GLYVCMNTFL AFGREHVERH FRKTGQSVYM HLKRHVREKV RGASGGALPK RRNSKIFLDL
DTDDDLNSDD YEYEDEAKLV IFPDHYEIAL PNIEELPALV TIACDAVLSS KSPYRKQDPD
TWENELPVSK YANNLTQLDN GVRIPPSGWK CARCDLRENL WLNLTDGSVL CGKWFFDSSG
GNGHALEHYR DMGYPLAVKL GTITPDGADV YSFQEEEPVL DPHLAKHLAH FGIDMLHMHG
TENGLQDNDI KLRVSEWEVI QESGTKLKPM YGPGYTGLKN LGNSCYLSSV MQAIFSIPEF
QRAYVGNLPR IFDYSPLDPT QDFNTQMTKL GHGLLSGQYS KPPVKSELIE QVMKEEHKPQ
QNGISPRMFK AFVSKSHPEF SSNRQQDAQE FFLHLVNLVE RNRIGSENPS DVFRFLVEER
IQCCQTRKVR YTERVDYLMQ LPVAMEAATN KDELIAYELT RREAEANRRP LPELVRAKIP
FSACLQAFSE PENVDDFWSS ALQAKSAGVK TSRFASFPEY LVVQIKKFTF GLDWVPKKFD
VSIDMPDLLD INHLRARGLQ PGEEELPDIS PPIVIPDDSK DRLMNQLIDP SDIDESSVMQ
LAEMGFPLEA CRKAVYFTGN MGAEVAFNWI IVHMEEPDFA EPLTMPGYGG AASAGASVFG
ASGLDNQPPE EIVAIITSMG FQRNQAIQAL RATNNNLERA LDWIFSHPEF EEDSDFVIEM
ENNANANIIS EAKPEGPRVK DGSGTYELFA FISHMGTSTM SGHYICHIKK EGRWVIYNDH
KVCASERPPK DLGYMYFYRR IPS
