UBP4_YEAST
ID UBP4_YEAST Reviewed; 926 AA.
AC P32571; D6VS55;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 4;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 4;
DE AltName: Full=Ubiquitin thioesterase 4;
DE AltName: Full=Ubiquitin-specific-processing protease 4;
DE AltName: Full=Vacuole biogenesis protein SSV7;
GN Name=DOA4; Synonyms=DOS1, MUT4, NPI2, SSV7, UBP4;
GN OrderedLocusNames=YDR069C; ORFNames=D4270, YD8554.02C, YD9609.23C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Latterich M.;
RL Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [4]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-926.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8789263;
RX DOI=10.1002/(sici)1097-0061(199601)12:1<85::aid-yea890>3.0.co;2-u;
RA Brandt P., Ramlow S., Otto B., Bloecker H.;
RT "Nucleotide sequence analysis of a 32,500 bp region of the right arm of
RT Saccharomyces cerevisiae chromosome IV.";
RL Yeast 12:85-90(1996).
RN [6]
RP FUNCTION.
RX PubMed=8657109; DOI=10.1128/mcb.16.4.1356;
RA Singer J.D., Manning B.M., Formosa T.;
RT "Coordinating DNA replication to produce one copy of the genome requires
RT genes that act in ubiquitin metabolism.";
RL Mol. Cell. Biol. 16:1356-1366(1996).
RN [7]
RP FUNCTION.
RX PubMed=9312043; DOI=10.1093/emboj/16.19.5847;
RA Galan J.-M., Haguenauer-Tsapis R.;
RT "Ubiquitin lys63 is involved in ubiquitination of a yeast plasma membrane
RT protein.";
RL EMBO J. 16:5847-5854(1997).
RN [8]
RP FUNCTION.
RX PubMed=9119204; DOI=10.1111/j.1574-6968.1997.tb10253.x;
RA Lucero P., Lagunas R.;
RT "Catabolite inactivation of the yeast maltose transporter requires
RT ubiquitin-ligase npi1/rsp5 and ubiquitin-hydrolase npi2/doa4.";
RL FEMS Microbiol. Lett. 147:273-277(1997).
RN [9]
RP FUNCTION.
RX PubMed=9447974; DOI=10.1128/mcb.18.2.779;
RA Loayza D., Michaelis S.;
RT "Role for the ubiquitin-proteasome system in the vacuolar degradation of
RT Ste6p, the a-factor transporter in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 18:779-789(1998).
RN [10]
RP FUNCTION.
RX PubMed=10194416; DOI=10.1242/jcs.112.9.1375;
RA Springael J.-Y., Galan J.-M., Haguenauer-Tsapis R., Andre B.;
RT "NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p
RT permease involves its ubiquitination with lysine-63-linked chains.";
RL J. Cell Sci. 112:1375-1383(1999).
RN [11]
RP ASSOCIATION WITH THE 26S PROTEASOME.
RX PubMed=10069815; DOI=10.1091/mbc.10.3.741;
RA Papa F.R., Amerik A.Y., Hochstrasser M.;
RT "Interaction of the Doa4 deubiquitinating enzyme with the yeast 26S
RT proteasome.";
RL Mol. Biol. Cell 10:741-756(1999).
RN [12]
RP FUNCTION.
RX PubMed=10436014; DOI=10.1091/mbc.10.8.2583;
RA Swaminathan S., Amerik A.Y., Hochstrasser M.;
RT "The Doa4 deubiquitinating enzyme is required for ubiquitin homeostasis in
RT yeast.";
RL Mol. Biol. Cell 10:2583-2594(1999).
RN [13]
RP FUNCTION.
RX PubMed=10207058; DOI=10.1128/mcb.19.5.3338;
RA Cooper K.F., Mallory M.J., Strich R.;
RT "Oxidative stress-induced destruction of the yeast C-type cyclin Ume3p
RT requires phosphatidylinositol-specific phospholipase C and the 26S
RT proteasome.";
RL Mol. Cell. Biol. 19:3338-3348(1999).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11029042; DOI=10.1091/mbc.11.10.3365;
RA Amerik A.Y., Nowak J., Swaminathan S., Hochstrasser M.;
RT "The Doa4 deubiquitinating enzyme is functionally linked to the vacuolar
RT protein-sorting and endocytic pathways.";
RL Mol. Biol. Cell 11:3365-3380(2000).
RN [15]
RP FUNCTION.
RX PubMed=11325936; DOI=10.1128/jb.183.10.3083-3088.2001;
RA Horak J., Wolf D.H.;
RT "Glucose-induced monoubiquitination of the Saccharomyces cerevisiae
RT galactose transporter is sufficient to signal its internalization.";
RL J. Bacteriol. 183:3083-3088(2001).
RN [16]
RP FUNCTION.
RX PubMed=11294906; DOI=10.1091/mbc.12.4.1047;
RA Losko S., Kopp F., Kranz A., Koelling R.;
RT "Uptake of the ATP-binding cassette (ABC) transporter Ste6 into the yeast
RT vacuole is blocked in the doa4 Mutant.";
RL Mol. Biol. Cell 12:1047-1059(2001).
RN [17]
RP FUNCTION.
RX PubMed=11416128; DOI=10.1128/mcb.21.14.4482-4494.2001;
RA Dupre S., Haguenauer-Tsapis R.;
RT "Deubiquitination step in the endocytic pathway of yeast plasma membrane
RT proteins: crucial role of Doa4p ubiquitin isopeptidase.";
RL Mol. Cell. Biol. 21:4482-4494(2001).
RN [18]
RP FUNCTION.
RX PubMed=14523026; DOI=10.1074/jbc.m306953200;
RA Nikko E., Marini A.-M., Andre B.;
RT "Permease recycling and ubiquitination status reveal a particular role for
RT Bro1 in the multivesicular body pathway.";
RL J. Biol. Chem. 278:50732-50743(2003).
RN [19]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [20]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [21]
RP FUNCTION.
RX PubMed=14990574; DOI=10.1074/jbc.m312338200;
RA Fiorani P., Reid R.J.D., Schepis A., Jacquiau H.R., Guo H., Thimmaiah P.,
RA Benedetti P., Bjornsti M.-A.;
RT "The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I
RT poisons.";
RL J. Biol. Chem. 279:21271-21281(2004).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRO1.
RX PubMed=15326198; DOI=10.1083/jcb.200403139;
RA Luhtala N., Odorizzi G.;
RT "Bro1 coordinates deubiquitination in the multivesicular body pathway by
RT recruiting Doa4 to endosomes.";
RL J. Cell Biol. 166:717-729(2004).
RN [23]
RP INTERACTION WITH VPS32.
RX PubMed=15086794; DOI=10.1111/j.1600-0854.2004.00169.x;
RA Bowers K., Lottridge J., Helliwell S.B., Goldthwaite L.M., Luzio J.P.,
RA Stevens T.H.;
RT "Protein-protein interactions of ESCRT complexes in the yeast Saccharomyces
RT cerevisiae.";
RL Traffic 5:194-210(2004).
RN [24]
RP SUBCELLULAR LOCATION.
RX PubMed=17130288; DOI=10.1083/jcb.200606113;
RA Nickerson D.P., West M., Odorizzi G.;
RT "Did2 coordinates Vps4-mediated dissociation of ESCRT-III from endosomes.";
RL J. Cell Biol. 175:715-720(2006).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=17145966; DOI=10.1083/jcb.200605134;
RA Amerik A.Y., Sindhi N., Hochstrasser M.;
RT "A conserved late endosome-targeting signal required for Doa4
RT deubiquitylating enzyme function.";
RL J. Cell Biol. 175:825-835(2006).
RN [26]
RP FUNCTION.
RX PubMed=16641373; DOI=10.1091/mbc.e05-07-0669;
RA Rubio-Texeira M., Kaiser C.A.;
RT "Amino acids regulate retrieval of the yeast general amino acid permease
RT from the vacuolar targeting pathway.";
RL Mol. Biol. Cell 17:3031-3050(2006).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BRO1, AND MUTAGENESIS OF
RP CYS-571; TYR-826; PRO-827 AND LEU-829.
RX PubMed=17446860; DOI=10.1038/sj.emboj.7601692;
RA Richter C., West M., Odorizzi G.;
RT "Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular
RT bodies.";
RL EMBO J. 26:2454-2464(2007).
RN [28]
RP INTERACTION WITH BRO1, AND SUBCELLULAR LOCATION.
RX PubMed=17513562; DOI=10.1128/ec.00024-07;
RA Nikko E., Andre B.;
RT "Split-ubiquitin two-hybrid assay to analyze protein-protein interactions
RT at the endosome: application to Saccharomyces cerevisiae Bro1 interacting
RT with ESCRT complexes, the Doa4 ubiquitin hydrolase, and the Rsp5 ubiquitin
RT ligase.";
RL Eukaryot. Cell 6:1266-1277(2007).
RN [29]
RP FUNCTION, AND MUTAGENESIS OF CYS-571.
RX PubMed=17376168; DOI=10.1111/j.1600-0854.2007.00553.x;
RA Nikko E., Andre B.;
RT "Evidence for a direct role of the Doa4 deubiquitinating enzyme in protein
RT sorting into the MVB pathway.";
RL Traffic 8:566-581(2007).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-443, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [31]
RP ACTIVITY REGULATION, AND INTERACTION WITH RFU1.
RX PubMed=19410548; DOI=10.1016/j.cell.2009.02.028;
RA Kimura Y., Yashiroda H., Kudo T., Koitabashi S., Murata S., Kakizuka A.,
RA Tanaka K.;
RT "An inhibitor of a deubiquitinating enzyme regulates ubiquitin
RT homeostasis.";
RL Cell 137:549-559(2009).
CC -!- FUNCTION: Ubiquitin thioesterase that acts at the late
CC endosome/prevacuolar compartment to recover ubiquitin from
CC ubiquitinated membrane proteins en route to the vacuole. Removes also
CC ubiquitin from soluble proteins targeted to proteasomes. Is essential
CC to maintain a normal level of free ubiquitin. Involved in the ammonium-
CC induced down-regulation of the GAP1 permease and the UME3 destruction
CC in response to oxidative stress. Has a role in the RAD9 checkpoint
CC response to TOP1 poisons. Required for promoting coordination of DNA
CC replication and avoids DNA overreplication.
CC {ECO:0000269|PubMed:10194416, ECO:0000269|PubMed:10207058,
CC ECO:0000269|PubMed:10436014, ECO:0000269|PubMed:11029042,
CC ECO:0000269|PubMed:11294906, ECO:0000269|PubMed:11325936,
CC ECO:0000269|PubMed:11416128, ECO:0000269|PubMed:14523026,
CC ECO:0000269|PubMed:14990574, ECO:0000269|PubMed:15326198,
CC ECO:0000269|PubMed:16641373, ECO:0000269|PubMed:17145966,
CC ECO:0000269|PubMed:17376168, ECO:0000269|PubMed:17446860,
CC ECO:0000269|PubMed:8247125, ECO:0000269|PubMed:8657109,
CC ECO:0000269|PubMed:9119204, ECO:0000269|PubMed:9312043,
CC ECO:0000269|PubMed:9447974}.
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: RFU1 is an inhibitor of deubiquitination activity.
CC {ECO:0000269|PubMed:19410548}.
CC -!- SUBUNIT: Interacts with BRO1, RFU1 and VPS32. Associates with the 26S
CC proteasome. {ECO:0000269|PubMed:15086794, ECO:0000269|PubMed:15326198,
CC ECO:0000269|PubMed:17446860, ECO:0000269|PubMed:17513562,
CC ECO:0000269|PubMed:19410548}.
CC -!- INTERACTION:
CC P32571; P48582: BRO1; NbExp=15; IntAct=EBI-19840, EBI-3768;
CC P32571; Q08003: RFU1; NbExp=2; IntAct=EBI-19840, EBI-2353109;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Late endosome membrane; Peripheral
CC membrane protein. Note=Recruited to the late endosome by BRO1.
CC -!- DOMAIN: Residues 1-208 are essential for the localization to the late
CC endosome and constitute a late endosome localization (LEL) domain.
CC {ECO:0000269|PubMed:17145966}.
CC -!- MISCELLANEOUS: Present with 428 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. {ECO:0000305}.
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DR EMBL; U02518; AAC48915.1; -; Genomic_DNA.
DR EMBL; L08070; AAA35105.1; -; Genomic_DNA.
DR EMBL; Z49209; CAA89098.1; -; Genomic_DNA.
DR EMBL; Z46796; CAA86791.1; -; Genomic_DNA.
DR EMBL; Z74365; CAA98887.1; -; Genomic_DNA.
DR EMBL; X84162; CAA58985.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11915.1; -; Genomic_DNA.
DR PIR; S39344; S39344.
DR RefSeq; NP_010354.3; NM_001180377.3.
DR AlphaFoldDB; P32571; -.
DR SMR; P32571; -.
DR BioGRID; 32124; 296.
DR DIP; DIP-5298N; -.
DR IntAct; P32571; 27.
DR MINT; P32571; -.
DR STRING; 4932.YDR069C; -.
DR MEROPS; C19.005; -.
DR TCDB; 3.A.31.1.1; the endosomal sorting complexes required for transport iii (escrt-iii) family.
DR CarbonylDB; P32571; -.
DR iPTMnet; P32571; -.
DR MaxQB; P32571; -.
DR PaxDb; P32571; -.
DR PRIDE; P32571; -.
DR EnsemblFungi; YDR069C_mRNA; YDR069C; YDR069C.
DR GeneID; 851641; -.
DR KEGG; sce:YDR069C; -.
DR SGD; S000002476; DOA4.
DR VEuPathDB; FungiDB:YDR069C; -.
DR eggNOG; KOG1868; Eukaryota.
DR GeneTree; ENSGT00940000174852; -.
DR HOGENOM; CLU_005922_1_0_1; -.
DR InParanoid; P32571; -.
DR OMA; KFFIDNR; -.
DR BioCyc; YEAST:G3O-29676-MON; -.
DR Reactome; R-SCE-1358803; Downregulation of ERBB2:ERBB3 signaling.
DR Reactome; R-SCE-5656169; Termination of translesion DNA synthesis.
DR PRO; PR:P32571; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P32571; protein.
DR GO; GO:0005829; C:cytosol; HDA:SGD.
DR GO; GO:0005768; C:endosome; IDA:SGD.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR GO; GO:0000502; C:proteasome complex; IDA:SGD.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:SGD.
DR GO; GO:1904669; P:ATP export; IMP:SGD.
DR GO; GO:0006897; P:endocytosis; IMP:SGD.
DR GO; GO:0010995; P:free ubiquitin chain depolymerization; IDA:SGD.
DR GO; GO:0070676; P:intralumenal vesicle formation; IGI:SGD.
DR GO; GO:0016579; P:protein deubiquitination; IEA:InterPro.
DR GO; GO:0006275; P:regulation of DNA replication; IMP:SGD.
DR GO; GO:0010992; P:ubiquitin recycling; IMP:SGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:SGD.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:SGD.
DR Gene3D; 3.40.250.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR Pfam; PF00581; Rhodanese; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
DR PROSITE; PS00972; USP_1; 1.
DR PROSITE; PS00973; USP_2; 1.
DR PROSITE; PS50235; USP_3; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; Hydrolase; Membrane; Phosphoprotein; Protease;
KW Reference proteome; Thiol protease; Ubl conjugation pathway.
FT CHAIN 1..926
FT /note="Ubiquitin carboxyl-terminal hydrolase 4"
FT /id="PRO_0000080589"
FT DOMAIN 205..328
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 562..923
FT /note="USP"
FT ACT_SITE 571
FT /note="Nucleophile"
FT ACT_SITE 880
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT MOD_RES 443
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 571
FT /note="C->S,A: Impairs deubiquitination activity and
FT protein sorting into the MVB pathway."
FT /evidence="ECO:0000269|PubMed:17376168,
FT ECO:0000269|PubMed:17446860"
FT MUTAGEN 826
FT /note="Y->A: Impairs deubiquitination activity and binding
FT to BRO1; when associated with A-827 and A-829."
FT /evidence="ECO:0000269|PubMed:17446860"
FT MUTAGEN 827
FT /note="P->A: Impairs deubiquitination activity and binding
FT to BRO1; when associated with A-826 and A-829."
FT /evidence="ECO:0000269|PubMed:17446860"
FT MUTAGEN 829
FT /note="L->A: Impairs deubiquitination activity and binding
FT to BRO1; when associated with A-826 and A-827."
FT /evidence="ECO:0000269|PubMed:17446860"
FT CONFLICT 327
FT /note="Q -> K (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="I -> F (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 375..378
FT /note="MLVA -> TASW (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="N -> I (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="K -> T (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 543..570
FT /note="LDHTDVTPTSSHNYDLDFAVGLENLGNS -> FRSYEMLHQLLLIIMTLISR
FT LVWENLEIP (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 580
FT /note="I -> T (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 836
FT /note="W -> G (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
FT CONFLICT 897
FT /note="D -> N (in Ref. 2; AAA35105)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 926 AA; 105192 MW; B863FE6062510F3C CRC64;
MEQNIISTIR DECIRHRSKY LTIAQLTAIA EAKINEFIIT GKAKDQDLSS LLDKCIDILS
IYKKNSKDIK NIISCKNKGA MISSNSVMII QLNYVYYKVI HIIVTTNIPH LSEFAKIKLH
KSTSDEGNGN NNNNEFQLMN IYNTLLETLL KDENIAKIKS FIKSSIKQTK LNHEQEECNL
MRTGSYITSN QLNSLISSSA NSASSQMEIL LIDIRSRLEF NKSHIDTKNI ICLEPISFKM
SYSDHDLEKK SLITSPNSEI KMFQSRNLFK FIILYTDANE YNVKQQSVLL DILVNHSFEK
PISDDFTKIF ILESGFPGWL KSNYGRQVSS SFPSNNNIKD DSVYINGNTS GLSLQHLPKM
SPSIRHSMDD SMKEMLVAPT PLNHLQQQQQ QQSDNDHVLK RSSSFKKLFS NYTSPNPKNS
NSNLYSISSL SISSSPSPLP LHSPDPVKGN SLPINYPETP HLWKNSETDF MTNQREQLNH
NSFAHIAPIN TKAITSPSRT ATPKLQRFPQ TISMNLNMNS NGHSSATSTI QPSCLSLSNN
DSLDHTDVTP TSSHNYDLDF AVGLENLGNS CYMNCIIQCI LGTHELTQIF LDDSYAKHIN
INSKLGSKGI LAKYFARLVH MMYKEQVDGS KKISISPIKF KLACGSVNSL FKTASQQDCQ
EFCQFLLDGL HEDLNQCGSN PPLKELSQEA EARREKLSLR IASSIEWERF LTTDFSVIVD
LFQGQYASRL KCKVCSHTST TYQPFTVLSI PIPKKNSRNN ITIEDCFREF TKCENLEVDE
QWLCPHCEKR QPSTKQLTIT RLPRNLIVHL KRFDNLLNKN NDFVIYPFLL DLTPFWANDF
DGVFPPGVND DELPIRGQIP PFKYELYGVA CHFGTLYGGH YTAYVKKGLK KGWLYFDDTK
YKPVKNKADA INSNAYVLFY HRVYGV
