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 27-MAR-2024, entry version 192. DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 13; DE EC=3.4.19.12 {ECO:0000269|PubMed:23940278, ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:33592542}; 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, CATALYTIC ACTIVITY, AND MUTAGENESIS OF MET-664 AND MET-739. RX PubMed=23940278; DOI=10.4049/jimmunol.1300225; RA Yeh H.M., Yu C.Y., Yang H.C., Ko S.H., Liao C.L., Lin Y.L.; RT "Ubiquitin-specific protease 13 regulates IFN signaling by stabilizing RT STAT1."; RL J. Immunol. 191:3328-3336(2013). RN [16] 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 [17] 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 [18] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28534493; DOI=10.1038/ncomms15534; RA Sun H., Zhang Q., Jing Y.Y., Zhang M., Wang H.Y., Cai Z., Liuyu T., RA Zhang Z.D., Xiong T.C., Wu Y., Zhu Q.Y., Yao J., Shu H.B., Lin D., RA Zhong B.; RT "USP13 negatively regulates antiviral responses by deubiquitinating RT STING."; RL Nat. Commun. 8:15534-15534(2017). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH NEDD4. RX PubMed=32101753; DOI=10.1016/j.celrep.2020.01.088; RA Xie W., Jin S., Wu Y., Xian H., Tian S., Liu D.A., Guo Z., Cui J.; RT "Auto-ubiquitination of NEDD4-1 Recruits USP13 to Facilitate Autophagy RT through Deubiquitinating VPS34."; RL Cell Rep. 30:2807-2819(2020). RN [20] RP FUNCTION, AND PHOSPHORYLATION AT SER-114. RX PubMed=32772043; DOI=10.1038/s41388-020-01396-8; RA Esposito M., Akman H.B., Giron P., Ceregido M.A., Schepers R., RA Ramos Paez L.C., La Monaca E., De Greve J., Coux O., De Trez C., Lindon C., RA Gutierrez G.J.; RT "USP13 controls the stability of Aurora B impacting progression through the RT cell cycle."; RL Oncogene 39:6009-6023(2020). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF CYS-345. RX PubMed=33592542; DOI=10.1016/j.dnarep.2021.103063; RA Kim W., Zhao F., Gao H., Qin S., Hou J., Deng M., Kloeber J.A., Huang J., RA Zhou Q., Guo G., Gao M., Zeng X., Zhu S., Tu X., Wu Z., Zhang Y., Yin P., RA Kaufmann S.H., Luo K., Lou Z.; RT "USP13 regulates the replication stress response by deubiquitinating RT TopBP1."; RL DNA Repair 100:103063-103063(2021). RN [22] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=36585612; DOI=10.1186/s10020-022-00596-0; RA Shin J., Kim Y.H., Lee B., Chang J.H., Choi H.Y., Lee H., Song K.C., RA Kwak M.S., Choi J.E., Shin J.S.; RT "USP13 regulates HMGB1 stability and secretion through its deubiquitinase RT activity."; RL Mol. Med. 28:164-164(2022). RN [23] 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, endoplasmic reticulum-associated CC degradation (ERAD), cell cycle progression or DNA damage response CC (PubMed:21571647, PubMed:32772043, PubMed:33592542). Component of a CC regulatory loop that controls autophagy and p53/TP53 levels: mediates CC deubiquitination of BECN1, a key regulator of autophagy, leading to CC stabilize the PIK3C3/VPS34-containing complexes. Alternatively, forms CC with NEDD4 a deubiquitination complex, which subsequently stabilizes CC VPS34 to promote autophagy (PubMed:32101753). Also deubiquitinates CC USP10, an essential regulator of p53/TP53 stability. In turn, CC PIK3C3/VPS34-containing complexes regulate USP13 stability, suggesting CC the existence of a regulatory system by which PIK3C3/VPS34-containing CC complexes regulate p53/TP53 protein levels via USP10 and USP13. CC Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, CC thereby regulating endoplasmic reticulum-associated degradation (ERAD). CC Also regulates ERAD through the deubiquitination of UBL4A a component CC of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently CC of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by CC impairing SIAH2 autoubiquitination. Regulates the cell cycle CC progression by stabilizing cell cycle proteins such as SKP2 and AURKB CC (PubMed:32772043). In addition, plays an important role in maintaining CC genomic stability and in DNA replication checkpoint activation via CC regulation of RAP80 and TOPBP1 (PubMed:33592542). Deubiquitinates the CC multifunctional protein HMGB1 and subsequently drives its CC nucleocytoplasmic localization and its secretion (PubMed:36585612). CC Positively regulates type I and type II interferon signalings by CC deubiquitinating STAT1 but negatively regulates antiviral response by CC deubiquitinating STING1 (PubMed:23940278, PubMed:28534493). 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, ECO:0000269|PubMed:28534493, CC ECO:0000269|PubMed:32101753, ECO:0000269|PubMed:32772043, CC ECO:0000269|PubMed:33592542, ECO:0000269|PubMed:36585612}. 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; Evidence={ECO:0000269|PubMed:23940278, CC ECO:0000269|PubMed:28534493, ECO:0000269|PubMed:33592542}; 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). Interacts with NEDD4 (PubMed:32101753). CC {ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, CC ECO:0000269|PubMed:24424410, ECO:0000269|PubMed:32101753}. 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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:36585612}. 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 -!- PTM: Phosphorylated by AURKB at Ser-114; leading to stabilization of CC cell cycle proteins such as SKP2 and AURKB, but not MCL1. CC {ECO:0000269|PubMed:32772043}. 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; 105. DR DIP; DIP-53511N; -. DR IntAct; Q92995; 44. 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; 9606-ENSP00000263966; -. DR PeptideAtlas; Q92995; -. DR ProteomicsDB; 75664; -. [Q92995-1] DR ProteomicsDB; 75665; -. [Q92995-2] DR Pumba; Q92995; -. DR Antibodypedia; 1352; 369 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 AGR; HGNC:12611; -. DR CTD; 8975; -. DR DisGeNET; 8975; -. DR GeneCards; USP13; -. DR HGNC; HGNC:12611; USP13. DR HPA; ENSG00000058056; Group enriched (heart muscle, 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; ASTECAY; -. DR OrthoDB; 166948at2759; -. 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 1199 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 205 other cell types or tissues. DR ExpressionAtlas; Q92995; baseline and differential. 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:0004843; F:cysteine-type deubiquitinase activity; IDA:UniProtKB. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB. DR GO; GO:1990380; F:K48-linked deubiquitinase activity; IMP:ParkinsonsUK-UCL. DR GO; GO:0070628; F:proteasome binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI: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:0036506; P:maintenance of unfolded protein; 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: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:0006508; P:proteolysis; IEA:UniProtKB-KW. DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. DR CDD; cd02658; Peptidase_C19B; 1. DR CDD; cd14384; UBA1_UBP13; 1. DR CDD; cd14386; UBA2_UBP5; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR21646; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1. DR PANTHER; PTHR21646:SF10; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 14; 1. 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; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF46934; UBA-like; 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. DR Genevisible; Q92995; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Cytoplasm; Hydrolase; KW Isopeptide bond; Metal-binding; Phosphoprotein; Protease; KW Reference proteome; Repeat; Thiol protease; Ubl conjugation; KW Ubl conjugation pathway; Zinc; 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; by AURKB" FT /evidence="ECO:0000269|PubMed:32772043, FT 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, ECO:0000269|PubMed:33592542" FT MUTAGEN 664 FT /note="M->E: Impairs ability to stabilize SIAH2 and STAT1. FT Abolishes ability to stabilize SIAH2 and STAT1; when FT associated with E-739." FT /evidence="ECO:0000269|PubMed:21659512" FT MUTAGEN 739 FT /note="M->E: Impairs ability to stabilize SIAH2 and STAT1. FT Abolishes ability to stabilize SIAH2 and STAT1; when FT 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 //