ID   UBP15_YEAST             Reviewed;        1230 AA.
AC   P50101; D6W0D1;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 15 {ECO:0000305};
DE            EC=3.4.19.12 {ECO:0000269|PubMed:21665945};
DE   AltName: Full=Deubiquitinating enzyme 15;
DE   AltName: Full=Ubiquitin thioesterase 15;
DE   AltName: Full=Ubiquitin-specific-processing protease 15;
GN   Name=UBP15 {ECO:0000303|PubMed:21665945, ECO:0000312|SGD:S000004920};
GN   OrderedLocusNames=YMR304W; ORFNames=YM9952.06;
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 [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169872;
RA   Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA   Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA   Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA   Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL   Nature 387:90-93(1997).
RN   [2]
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   [3]
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PEX6,
RP   ACTIVE SITE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF CYS-214.
RX   PubMed=21665945; DOI=10.1074/jbc.m111.238600;
RA   Debelyy M.O., Platta H.W., Saffian D., Hensel A., Thoms S., Meyer H.E.,
RA   Warscheid B., Girzalsky W., Erdmann R.;
RT   "Ubp15p, a ubiquitin hydrolase associated with the peroxisomal export
RT   machinery.";
RL   J. Biol. Chem. 286:28223-28234(2011).
CC   -!- FUNCTION: Deubiquitinase involved in peroxisome import by mediating
CC       deubiquitination of the peroxisomal import receptor PEX5
CC       (PubMed:21665945). Catalyzes deubiquitination of both monoubiquitiated
CC       and polyubiquitinated forms of PEX5 following its retrotranslocation
CC       into the cytosol, resetting PEX5 for a subsequent import cycle
CC       (PubMed:21665945). {ECO:0000269|PubMed:21665945}.
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:21665945};
CC   -!- SUBUNIT: Interacts with PEX6; promoting association with the PEX1-PEX6
CC       ATPase complex. {ECO:0000269|PubMed:21665945}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21665945}.
CC       Peroxisome {ECO:0000269|PubMed:21665945}.
CC   -!- DISRUPTION PHENOTYPE: Cells show oxidative stress-related import
CC       deficiencies and growth defect on oleic acid (PubMed:21665945).
CC       Peroxisomes are clustered (PubMed:21665945). Cells display defects in
CC       peroxisomal import of proteins containing a C-terminal PTS1-type
CC       tripeptide peroxisomal targeting signal (SKL-type) (PubMed:21665945).
CC       {ECO:0000269|PubMed:21665945}.
CC   -!- MISCELLANEOUS: Present with 2810 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; Z49212; CAA89137.1; -; Genomic_DNA.
DR   EMBL; BK006946; DAA10205.1; -; Genomic_DNA.
DR   PIR; S53974; S53974.
DR   RefSeq; NP_014033.1; NM_001182814.1.
DR   AlphaFoldDB; P50101; -.
DR   SMR; P50101; -.
DR   BioGRID; 35484; 255.
DR   DIP; DIP-6313N; -.
DR   IntAct; P50101; 26.
DR   MINT; P50101; -.
DR   STRING; 4932.YMR304W; -.
DR   MEROPS; C19.099; -.
DR   iPTMnet; P50101; -.
DR   MaxQB; P50101; -.
DR   PaxDb; 4932-YMR304W; -.
DR   PeptideAtlas; P50101; -.
DR   EnsemblFungi; YMR304W_mRNA; YMR304W; YMR304W.
DR   GeneID; 855350; -.
DR   KEGG; sce:YMR304W; -.
DR   AGR; SGD:S000004920; -.
DR   SGD; S000004920; UBP15.
DR   VEuPathDB; FungiDB:YMR304W; -.
DR   eggNOG; KOG1863; Eukaryota.
DR   HOGENOM; CLU_003532_2_1_1; -.
DR   InParanoid; P50101; -.
DR   OMA; DTDWGFA; -.
DR   OrthoDB; 51419at2759; -.
DR   BioCyc; YEAST:G3O-32969-MONOMER; -.
DR   Reactome; R-SCE-6782135; Dual incision in TC-NER.
DR   Reactome; R-SCE-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR   BioGRID-ORCS; 855350; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P50101; -.
DR   Proteomes; UP000002311; Chromosome XIII.
DR   RNAct; P50101; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005829; C:cytosol; IDA:SGD.
DR   GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005777; C:peroxisome; IDA:SGD.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:SGD.
DR   GO; GO:0010995; P:free ubiquitin chain depolymerization; IDA:SGD.
DR   GO; GO:0016579; P:protein deubiquitination; IDA:SGD.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0031647; P:regulation of protein stability; IBA:GO_Central.
DR   CDD; cd03775; MATH_Ubp21p; 1.
DR   CDD; cd02659; peptidase_C19C; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   InterPro; IPR002083; MATH/TRAF_dom.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR008974; TRAF-like.
DR   InterPro; IPR024729; USP7_ICP0-binding_dom.
DR   InterPro; IPR029346; USP_C.
DR   InterPro; IPR018200; USP_CS.
DR   InterPro; IPR028889; USP_dom.
DR   PANTHER; PTHR24006; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR24006:SF644; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 7; 1.
DR   Pfam; PF00443; UCH; 1.
DR   Pfam; PF14533; USP7_C2; 1.
DR   Pfam; PF12436; USP7_ICP0_bdg; 1.
DR   SMART; SM00061; MATH; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF49599; TRAF domain-like; 1.
DR   PROSITE; PS50144; MATH; 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; Hydrolase; Peroxisome; Protease; Reference proteome;
KW   Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..1230
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 15"
FT                   /id="PRO_0000080600"
FT   DOMAIN          39..179
FT                   /note="MATH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00129"
FT   DOMAIN          205..536
FT                   /note="USP"
FT   ACT_SITE        214
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093,
FT                   ECO:0000305|PubMed:21665945"
FT   ACT_SITE        465
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   MUTAGEN         214
FT                   /note="C->A: Abolished deubiquitinase activity."
FT                   /evidence="ECO:0000269|PubMed:21665945"
SQ   SEQUENCE   1230 AA;  143564 MW;  BEB8F6E3DD71A0CC CRC64;
     MSSEDELGSI GTVFPGSPID KSIGSILPQF DEEVETLLED SFTWNIPDWN ELTNPKYNSP
     RFRIGDFEWD ILLFPQGNHN KGVAVYLEPH PEEKLDETTG EMVPVDPDWY CCAQFAIGIS
     RPGNGDTINL INKSHHRFNA LDTDWGFANL IDLNNLKHPS KGRPLSFLNE GTLNITAYVR
     ILKDPTGVLW HNFLNYDSKK VTGYVGFRNQ GATCYLNSLL QSYFFTKYFR KLVYEIPTEH
     ESPNNSVPLA LQRAFYQLQV SDIPLDTLEL TRSFGWDTAE SFTQHDVQEL NRILMDRLEN
     NMKGTPVEGK LNEIFVGKMK SYIKCINVDY ESARVEDFWD LQLNVKNFKN LQESFDNYIE
     MELMNGENQY AAQDYGLQDA QKGVIFESFP PVLHLQLKRF EYDFNYDQMV KVNDKYEFPE
     TIDLSPFVDK DVLKKTLDSE NKDKNPYVYN LHGVLVHSGD ISTGHYYTLI KPGVEDQWYR
     FDDERVWRVT KKQVFQENFG CDRLPDEKVR TMTRGEYQNY IIQRHTSAYM LVYIRQEQEE
     DLLRPVLESD VPKHVITRVR EEIKERETKE KEIREAHLYV TLRLHSIKEF IHYEGFDYFA
     HDGFRLFAEE LNDSGLQQIN LKVLRTTKLS DIFASIKETM NIPQERDVKY WKMDYRRNST
     LRLTQPINFE SVNITLQEAL KKEKKRTMQT QYGEEGVAST EEDDKALLET VSFLDLFIEE
     PYLELQFLNK LKEASLISKA QLDDELISTI RTNLPELTKG GIEPVFATDN KSNLLFVKSY
     DPHTQKLLGF GHFAVNQLQQ LSDISAIIED SISSNEKLTF YEEVQPGTIN EIYMKETIYD
     ADIDTGDIVS FEVPGAVLPD TFPVYATIKD FYSYLRYRVK LKFSKFDGSS EEYGVSNEIP
     ESFEFWISAY APYDDLARMV SKYAHVKPEY LKIIALYSNG RFVLKSTSLL NDYLLKDFNC
     DQIPPFAFEV LSVPLKELER LRPIKLYWLK NSYIHYQCFE FEVANDYTES QFLEKVQHKI
     GFTDEEKENI LLWTNTNFQF QGLLSDQNTF KDVSKHSLLF GRILPEESKL FKELNRLENV
     QTSSLEDFMD DENATDRPMD DEQDLGMAIE HSEDMKGRIV VVQQYFKDLE NRHGISFLFN
     LIPDETFPKT KDRLHAKFGL GQKEFSKIKL SIGYSTEEGT VFRSLQGFSD EELDKVILYD
     IMSNLDYIYM DHPDRLRSHS SYDRPMIIKN
//