UBP5_HUMAN
ID UBP5_HUMAN Reviewed; 858 AA.
AC P45974; D3DUS7; D3DUS8; Q96J22;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 5;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 5;
DE AltName: Full=Isopeptidase T;
DE AltName: Full=Ubiquitin thioesterase 5;
DE AltName: Full=Ubiquitin-specific-processing protease 5;
GN Name=USP5; Synonyms=ISOT;
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], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7498549; DOI=10.1016/0014-5793(95)01287-7;
RA Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K., Jaton J.-C.;
RT "cDNA cloning of a human 100 kDa de-ubiquitinating enzyme: the 100 kDa
RT human de-ubiquitinase belongs to the ubiquitin C-terminal hydrolase family
RT 2 (UCH2).";
RL FEBS Lett. 376:233-237(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=8723724; DOI=10.1101/gr.6.4.314;
RA Ansari-Lari M.A., Muzny D.M., Lu J., Lu F., Lilley C.E., Spanos S.,
RA Malley T., Gibbs R.A.;
RT "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at
RT human chromosome 12p13.";
RL Genome Res. 6:314-326(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Tashayev V.L., O'Connor L.B., Larsen C.N., Kasperek E., Pickart C.M.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND SHORT).
RC TISSUE=Kidney, and Lung;
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 [7]
RP CHARACTERIZATION.
RX PubMed=7851534; DOI=10.1016/0014-5793(94)01451-6;
RA Falquet L., Paquet N., Frutiger S., Hughes G.J., Hoang-Van K., Jaton J.-C.;
RT "A human de-ubiquitinating enzyme with both isopeptidase and peptidase
RT activities in vitro.";
RL FEBS Lett. 359:73-77(1995).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP MUTAGENESIS OF ARG-221; CYS-335; ASP-435; MET-666 AND MET-734, AND
RP POLYUBIQUITIN BINDING.
RX PubMed=18482987; DOI=10.1074/jbc.m800947200;
RA Reyes-Turcu F.E., Shanks J.R., Komander D., Wilkinson K.D.;
RT "Recognition of polyubiquitin isoforms by the multiple ubiquitin binding
RT modules of isopeptidase T.";
RL J. Biol. Chem. 283:19581-19592(2008).
RN [10]
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP FUNCTION.
RX PubMed=19098288; DOI=10.1074/jbc.m805871200;
RA Dayal S., Sparks A., Jacob J., Allende-Vega N., Lane D.P., Saville M.K.;
RT "Suppression of the deubiquitinating enzyme USP5 causes the accumulation of
RT unanchored polyubiquitin and the activation of p53.";
RL J. Biol. Chem. 284:5030-5041(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, AND IDENTIFICATION BY
RP 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-783, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP MUTAGENESIS OF 221-ARG--TYR-223 AND TYR-261.
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).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-292; SER-779; SER-783 AND
RP SER-785, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 163-291 IN COMPLEX WITH
RP UBIQUITIN, ZINC-BINDING, AND MUTAGENESIS OF CYS-199; CYS-202; CYS-219 AND
RP HIS-232.
RX PubMed=16564012; DOI=10.1016/j.cell.2006.02.038;
RA Reyes-Turcu F.E., Horton J.R., Mullally J.E., Heroux A., Cheng X.,
RA Wilkinson K.D.;
RT "The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine
RT motif of unanchored ubiquitin.";
RL Cell 124:1197-1208(2006).
RN [22]
RP STRUCTURE BY NMR OF 655-772.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the first and second UBA domains in the human
RT ubiquitin specific protease 5 (isopeptidase 5).";
RL Submitted (JUN-2006) to the PDB data bank.
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1-858 IN COMPLEX WITH UBIQUITIN,
RP DISULFIDE BOND, AND ZINC-BINDING.
RA Walker J.R., Avvakumov G.V., Xue S., Butler-Cole C., Weigelt J.,
RA Bountra C., Arrowsmith C.H., Edwards A.M., Bochkarev A., Dhe-Paganon S.;
RT "Covalent ubiquitin-USP5 complex.";
RL Submitted (DEC-2009) to the PDB data bank.
CC -!- FUNCTION: Cleaves linear and branched multiubiquitin polymers with a
CC marked preference for branched polymers. Involved in unanchored 'Lys-
CC 48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked
CC polyubiquitin with a lower affinity. Knock-down of USP5 causes the
CC accumulation of p53/TP53 and an increase in p53/TP53 transcriptional
CC activity because the unanchored polyubiquitin that accumulates is able
CC to compete with ubiquitinated p53/TP53 but not with MDM2 for
CC proteasomal recognition. {ECO:0000269|PubMed:19098288}.
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 TRIML1. {ECO:0000250}.
CC -!- INTERACTION:
CC P45974; Q15038: DAZAP2; NbExp=3; IntAct=EBI-741277, EBI-724310;
CC P45974; P54727: RAD23B; NbExp=2; IntAct=EBI-741277, EBI-954531;
CC P45974; O75528: TADA3; NbExp=2; IntAct=EBI-741277, EBI-473249;
CC P45974; Q8WW34: TMEM239; NbExp=3; IntAct=EBI-741277, EBI-9675724;
CC P45974-2; Q9NWF9: RNF216; NbExp=3; IntAct=EBI-12072186, EBI-723313;
CC P45974-2; Q8N0X7: SPART; NbExp=3; IntAct=EBI-12072186, EBI-2643803;
CC P45974-2; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-12072186, EBI-11528917;
CC P45974-2; O14773: TPP1; NbExp=3; IntAct=EBI-12072186, EBI-2800203;
CC P45974-2; Q9BZR9: TRIM8; NbExp=3; IntAct=EBI-12072186, EBI-2340370;
CC P45974-2; P0CG47: UBB; NbExp=3; IntAct=EBI-12072186, EBI-413034;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P45974-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P45974-2; Sequence=VSP_005259;
CC -!- DOMAIN: The UBP-type zinc finger domain interacts selectively with an
CC unmodified C-terminus of the proximal ubiquitin. Both UBA domains are
CC involved in polyubiquitin recognition.
CC -!- MISCELLANEOUS: The UBP-type zinc finger domain crystallizes as a dimer
CC linked by a disulfide bond between the Cys-195 residues of both
CC molecules, but there is no evidence that the full-length USP5 exists as
CC a dimer.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; X91349; CAA62690.1; -; mRNA.
DR EMBL; U47927; AAC50465.1; -; mRNA.
DR EMBL; U47924; AAB51314.1; -; Genomic_DNA.
DR EMBL; U47924; AAB51315.1; -; Genomic_DNA.
DR EMBL; U35116; AAA78934.1; -; mRNA.
DR EMBL; CH471116; EAW88724.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88725.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88726.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88727.1; -; Genomic_DNA.
DR EMBL; BC004889; AAH04889.1; -; mRNA.
DR EMBL; BC005139; AAH05139.1; -; mRNA.
DR CCDS; CCDS31733.1; -. [P45974-2]
DR CCDS; CCDS41743.1; -. [P45974-1]
DR PIR; S68227; S68227.
DR RefSeq; NP_001092006.1; NM_001098536.1. [P45974-1]
DR RefSeq; NP_003472.2; NM_003481.2. [P45974-2]
DR PDB; 2DAG; NMR; -; A=655-715.
DR PDB; 2DAK; NMR; -; A=723-772.
DR PDB; 2G43; X-ray; 2.09 A; A/B=163-291.
DR PDB; 2G45; X-ray; 1.99 A; A/D=163-291.
DR PDB; 3IHP; X-ray; 2.80 A; A/B=1-858.
DR PDB; 6DXH; X-ray; 2.00 A; A=171-290.
DR PDB; 6DXT; X-ray; 1.95 A; A/B=171-290.
DR PDB; 6NFT; X-ray; 1.65 A; A/B=171-290.
DR PDB; 6P9G; X-ray; 2.10 A; A=171-290.
DR PDB; 7MS5; X-ray; 1.98 A; A/B=171-290.
DR PDB; 7MS6; X-ray; 1.55 A; A=171-290.
DR PDB; 7MS7; X-ray; 1.45 A; A/B=171-290.
DR PDBsum; 2DAG; -.
DR PDBsum; 2DAK; -.
DR PDBsum; 2G43; -.
DR PDBsum; 2G45; -.
DR PDBsum; 3IHP; -.
DR PDBsum; 6DXH; -.
DR PDBsum; 6DXT; -.
DR PDBsum; 6NFT; -.
DR PDBsum; 6P9G; -.
DR PDBsum; 7MS5; -.
DR PDBsum; 7MS6; -.
DR PDBsum; 7MS7; -.
DR AlphaFoldDB; P45974; -.
DR SMR; P45974; -.
DR BioGRID; 113751; 130.
DR DIP; DIP-34459N; -.
DR IntAct; P45974; 26.
DR MINT; P45974; -.
DR STRING; 9606.ENSP00000229268; -.
DR BindingDB; P45974; -.
DR ChEMBL; CHEMBL6158; -.
DR GuidetoPHARMACOLOGY; 2431; -.
DR MEROPS; C19.001; -.
DR GlyGen; P45974; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P45974; -.
DR MetOSite; P45974; -.
DR PhosphoSitePlus; P45974; -.
DR SwissPalm; P45974; -.
DR BioMuta; USP5; -.
DR DMDM; 1717869; -.
DR REPRODUCTION-2DPAGE; IPI00375145; -.
DR CPTAC; CPTAC-603; -.
DR CPTAC; CPTAC-604; -.
DR EPD; P45974; -.
DR jPOST; P45974; -.
DR MassIVE; P45974; -.
DR MaxQB; P45974; -.
DR PaxDb; P45974; -.
DR PeptideAtlas; P45974; -.
DR PRIDE; P45974; -.
DR ProteomicsDB; 55692; -. [P45974-1]
DR ProteomicsDB; 55693; -. [P45974-2]
DR Antibodypedia; 1723; 396 antibodies from 31 providers.
DR DNASU; 8078; -.
DR Ensembl; ENST00000229268.13; ENSP00000229268.8; ENSG00000111667.14. [P45974-1]
DR Ensembl; ENST00000389231.9; ENSP00000373883.5; ENSG00000111667.14. [P45974-2]
DR GeneID; 8078; -.
DR KEGG; hsa:8078; -.
DR MANE-Select; ENST00000229268.13; ENSP00000229268.8; NM_001098536.2; NP_001092006.1.
DR UCSC; uc001qrh.5; human. [P45974-1]
DR CTD; 8078; -.
DR DisGeNET; 8078; -.
DR GeneCards; USP5; -.
DR HGNC; HGNC:12628; USP5.
DR HPA; ENSG00000111667; Low tissue specificity.
DR MIM; 601447; gene.
DR neXtProt; NX_P45974; -.
DR OpenTargets; ENSG00000111667; -.
DR PharmGKB; PA37253; -.
DR VEuPathDB; HostDB:ENSG00000111667; -.
DR eggNOG; KOG0944; Eukaryota.
DR GeneTree; ENSGT00940000156036; -.
DR HOGENOM; CLU_009884_1_0_1; -.
DR InParanoid; P45974; -.
DR OMA; FDERQAV; -.
DR PhylomeDB; P45974; -.
DR TreeFam; TF300576; -.
DR BRENDA; 3.4.19.12; 2681.
DR PathwayCommons; P45974; -.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8866652; Synthesis of active ubiquitin: roles of E1 and E2 enzymes.
DR SignaLink; P45974; -.
DR BioGRID-ORCS; 8078; 703 hits in 1083 CRISPR screens.
DR ChiTaRS; USP5; human.
DR EvolutionaryTrace; P45974; -.
DR GeneWiki; USP5; -.
DR GenomeRNAi; 8078; -.
DR Pharos; P45974; Tchem.
DR PRO; PR:P45974; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P45974; protein.
DR Bgee; ENSG00000111667; Expressed in prefrontal cortex and 185 other tissues.
DR ExpressionAtlas; P45974; baseline and differential.
DR Genevisible; P45974; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005764; C:lysosome; TAS:ProtInc.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0043130; F:ubiquitin binding; IDA:ParkinsonsUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; IDA:ParkinsonsUK-UCL.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; TAS:Reactome.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR CDD; cd14383; UBA1_UBP5; 1.
DR Gene3D; 3.30.40.10; -; 3.
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; IPR041812; UBP5_UBA1.
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; Acetylation; Alternative splicing; Direct protein sequencing;
KW Disulfide bond; Hydrolase; Metal-binding; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..858
FT /note="Ubiquitin carboxyl-terminal hydrolase 5"
FT /id="PRO_0000080623"
FT DOMAIN 326..856
FT /note="USP"
FT DOMAIN 654..695
FT /note="UBA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 722..762
FT /note="UBA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 175..283
FT /note="UBP-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 74..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 75..89
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 335
FT /note="Nucleophile"
FT ACT_SITE 818
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 199
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 202
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 209
FT /ligand="substrate"
FT BINDING 219
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 221..224
FT /ligand="substrate"
FT BINDING 232
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 259
FT /ligand="substrate"
FT BINDING 261
FT /ligand="substrate"
FT BINDING 264
FT /ligand="substrate"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 292
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 623
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P56399"
FT MOD_RES 779
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 783
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 785
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 195..816
FT /evidence="ECO:0000269|Ref.23"
FT VAR_SEQ 629..652
FT /note="GSLGFYGNEDEDSFCSPHFSSPTS -> A (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005259"
FT MUTAGEN 199
FT /note="C->A: Decreased rate of activity and decreased zinc
FT binding."
FT /evidence="ECO:0000269|PubMed:16564012"
FT MUTAGEN 202
FT /note="C->A: Decreased rate of activity."
FT /evidence="ECO:0000269|PubMed:16564012"
FT MUTAGEN 219
FT /note="C->A: Decreased rate of activity."
FT /evidence="ECO:0000269|PubMed:16564012"
FT MUTAGEN 221..223
FT /note="RRY->KWF: Loss of polyubiquitin binding and
FT subsequent activation."
FT /evidence="ECO:0000269|PubMed:22216260"
FT MUTAGEN 221
FT /note="R->A: Loss of polyubiquitin hydrolysis. Loss of
FT ubiquitin binding; when associated with A-335."
FT /evidence="ECO:0000269|PubMed:18482987"
FT MUTAGEN 232
FT /note="H->A: Decreased rate of activity."
FT /evidence="ECO:0000269|PubMed:16564012"
FT MUTAGEN 261
FT /note="Y->F: Loss of polyubiquitin binding."
FT /evidence="ECO:0000269|PubMed:22216260"
FT MUTAGEN 335
FT /note="C->A: Loss of activity. Loss of ubiquitin binding;
FT when associated with A-221. Lower affinity for triubiquitin
FT and tetraubiquitin, but no effect on affinity for
FT diubiquitin; when associated with E-666. Lower affinity for
FT diubiquitin, triubiquitin and tetraubiquitin; when
FT associated with E-734."
FT /evidence="ECO:0000269|PubMed:18482987"
FT MUTAGEN 435
FT /note="D->A: Loss of polyubiquitin binding and hydrolysis."
FT /evidence="ECO:0000269|PubMed:18482987"
FT MUTAGEN 666
FT /note="M->E: Lower affinity for triubiquitin and
FT tetraubiquitin, but no effect on affinity for diubiquitin;
FT when associated with A-335. No effect on activity; when
FT associated with E-734."
FT /evidence="ECO:0000269|PubMed:18482987"
FT MUTAGEN 734
FT /note="M->E: Lower affinity for diubiquitin, triubiquitin
FT and tetraubiquitin; when associated with A-335. No effect
FT on activity; when associated with E-666."
FT /evidence="ECO:0000269|PubMed:18482987"
FT CONFLICT 3..4
FT /note="EL -> DV (in Ref. 1; CAA62690)"
FT /evidence="ECO:0000305"
FT CONFLICT 45
FT /note="I -> V (in Ref. 1; CAA62690)"
FT /evidence="ECO:0000305"
FT CONFLICT 468
FT /note="K -> R (in Ref. 4; AAA78934)"
FT /evidence="ECO:0000305"
FT CONFLICT 681
FT /note="G -> D (in Ref. 4; AAA78934)"
FT /evidence="ECO:0000305"
FT HELIX 5..11
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 12..15
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 58..65
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 69..75
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 118..124
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 125..128
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 141..154
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 178..182
FT /evidence="ECO:0007829|PDB:7MS7"
FT STRAND 200..203
FT /evidence="ECO:0007829|PDB:7MS7"
FT STRAND 206..211
FT /evidence="ECO:0007829|PDB:7MS7"
FT TURN 212..214
FT /evidence="ECO:0007829|PDB:7MS7"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:7MS7"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:7MS7"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:7MS7"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:7MS7"
FT TURN 261..264
FT /evidence="ECO:0007829|PDB:7MS7"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:7MS7"
FT HELIX 272..277
FT /evidence="ECO:0007829|PDB:7MS7"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:7MS7"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:2G45"
FT HELIX 335..344
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 348..354
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 358..364
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 373..385
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 415..421
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 422..424
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 426..429
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 436..449
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 457..460
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 463..471
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 472..475
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 476..489
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 493..495
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 499..514
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 529..537
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 540..547
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 548..551
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 552..564
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 567..573
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 576..578
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 580..582
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 584..586
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 595..598
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 600..602
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 658..666
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 670..679
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 685..695
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 700..702
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 725..732
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 733..735
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 738..747
FT /evidence="ECO:0007829|PDB:3IHP"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:3IHP"
FT HELIX 752..770
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 799..812
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 818..825
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 828..833
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 836..839
FT /evidence="ECO:0007829|PDB:3IHP"
FT STRAND 849..855
FT /evidence="ECO:0007829|PDB:3IHP"
SQ SEQUENCE 858 AA; 95786 MW; E99CB7CDFA682C65 CRC64;
MAELSEEALL SVLPTIRVPK AGDRVHKDEC AFSFDTPESE GGLYICMNTF LGFGKQYVER
HFNKTGQRVY LHLRRTRRPK EEDPATGTGD PPRKKPTRLA IGVEGGFDLS EEKFELDEDV
KIVILPDYLE IARDGLGGLP DIVRDRVTSA VEALLSADSA SRKQEVQAWD GEVRQVSKHA
FSLKQLDNPA RIPPCGWKCS KCDMRENLWL NLTDGSILCG RRYFDGSGGN NHAVEHYRET
GYPLAVKLGT ITPDGADVYS YDEDDMVLDP SLAEHLSHFG IDMLKMQKTD KTMTELEIDM
NQRIGEWELI QESGVPLKPL FGPGYTGIRN LGNSCYLNSV VQVLFSIPDF QRKYVDKLEK
IFQNAPTDPT QDFSTQVAKL GHGLLSGEYS KPVPESGDGE RVPEQKEVQD GIAPRMFKAL
IGKGHPEFST NRQQDAQEFF LHLINMVERN CRSSENPNEV FRFLVEEKIK CLATEKVKYT
QRVDYIMQLP VPMDAALNKE ELLEYEEKKR QAEEEKMALP ELVRAQVPFS SCLEAYGAPE
QVDDFWSTAL QAKSVAVKTT RFASFPDYLV IQIKKFTFGL DWVPKKLDVS IEMPEELDIS
QLRGTGLQPG EEELPDIAPP LVTPDEPKGS LGFYGNEDED SFCSPHFSSP TSPMLDESVI
IQLVEMGFPM DACRKAVYYT GNSGAEAAMN WVMSHMDDPD FANPLILPGS SGPGSTSAAA
DPPPEDCVTT IVSMGFSRDQ ALKALRATNN SLERAVDWIF SHIDDLDAEA AMDISEGRSA
ADSISESVPV GPKVRDGPGK YQLFAFISHM GTSTMCGHYV CHIKKEGRWV IYNDQKVCAS
EKPPKDLGYI YFYQRVAS
