ID   UBP6_YEAST              Reviewed;         499 AA.
AC   P43593; D6VTP0;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   04-NOV-2026, entry version 215.
DE   RecName: Full=Ubiquitin carboxyl-terminal hydrolase 6;
DE            EC=3.4.19.12;
DE   AltName: Full=Deubiquitinating enzyme 6;
DE   AltName: Full=Ubiquitin thioesterase 6;
DE   AltName: Full=Ubiquitin-specific-processing protease 6;
GN   Name=UBP6; OrderedLocusNames=YFR010W;
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=7670463; DOI=10.1038/ng0795-261;
RA   Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA   Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA   Eki T.;
RT   "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT   cerevisiae.";
RL   Nat. Genet. 10:261-268(1995).
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   FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=9344467; DOI=10.1006/abbi.1997.0311;
RA   Park K.C., Woo S.K., Yoo Y.J., Wyndham A.M., Baker R.T., Chung C.H.;
RT   "Purification and characterization of UBP6, a new ubiquitin-specific
RT   protease in Saccharomyces cerevisiae.";
RL   Arch. Biochem. Biophys. 347:78-84(1997).
RN   [4]
RP   FUNCTION.
RX   PubMed=10527495; DOI=10.1006/abio.1999.4234;
RA   Layfield R., Franklin K., Landon M., Walker G., Wang P., Ramage R.,
RA   Brown A., Love S., Urquhart K., Muir T., Baker R., Mayer R.J.;
RT   "Chemically synthesized ubiquitin extension proteins detect distinct
RT   catalytic capacities of deubiquitinating enzymes.";
RL   Anal. Biochem. 274:40-49(1999).
RN   [5]
RP   DOMAIN.
RX   PubMed=10386876; DOI=10.1110/ps.8.6.1268;
RA   Wyndham A.M., Baker R.T., Chelvanayagam G.;
RT   "The Ubp6 family of deubiquitinating enzymes contains a ubiquitin-like
RT   domain: SUb.";
RL   Protein Sci. 8:1268-1275(1999).
RN   [6]
RP   ASSOCIATION WITH THE 26S PROTEASOME, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=11029046; DOI=10.1091/mbc.11.10.3425;
RA   Verma R., Chen S., Feldman R., Schieltz D., Yates J., Dohmen J.,
RA   Deshaies R.J.;
RT   "Proteasomal proteomics: identification of nucleotide-sensitive proteasome-
RT   interacting proteins by mass spectrometric analysis of affinity-purified
RT   proteasomes.";
RL   Mol. Biol. Cell 11:3425-3439(2000).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY, ASSOCIATION WITH THE 26S PROTEASOME,
RP   FUNCTION, ACTIVITY REGULATION, AND DOMAIN.
RX   PubMed=12408819; DOI=10.1016/s1097-2765(02)00638-x;
RA   Leggett D.S., Hanna J., Borodovsky A., Crosas B., Schmidt M., Baker R.T.,
RA   Walz T., Ploegh H., Finley D.;
RT   "Multiple associated proteins regulate proteasome structure and function.";
RL   Mol. Cell 10:495-507(2002).
RN   [8]
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   [9]
RP   FUNCTION.
RX   PubMed=14581483; DOI=10.1074/jbc.m307050200;
RA   Guterman A., Glickman M.H.;
RT   "Complementary roles for Rpn11 and Ubp6 in deubiquitination and proteolysis
RT   by the proteasome.";
RL   J. Biol. Chem. 279:1729-1738(2004).
RN   [10]
RP   FUNCTION.
RX   PubMed=17018280; DOI=10.1016/j.cell.2006.07.038;
RA   Hanna J., Hathaway N.A., Tone Y., Crosas B., Elsasser S., Kirkpatrick D.S.,
RA   Leggett D.S., Gygi S.P., King R.W., Finley D.;
RT   "Deubiquitinating enzyme Ubp6 functions noncatalytically to delay
RT   proteasomal degradation.";
RL   Cell 127:99-111(2006).
RN   [11]
RP   FUNCTION.
RX   PubMed=17190603; DOI=10.1016/j.cell.2006.09.051;
RA   Crosas B., Hanna J., Kirkpatrick D.S., Zhang D.P., Tone Y., Hathaway N.A.,
RA   Buecker C., Leggett D.S., Schmidt M., King R.W., Gygi S.P., Finley D.;
RT   "Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin
RT   ligase and deubiquitinating activities.";
RL   Cell 127:1401-1413(2006).
RN   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389 AND SER-470, AND
RP   IDENTIFICATION BY 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   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389, AND IDENTIFICATION BY
RP   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   [15]
RP   IDENTIFICATION BY MASS SPECTROMETRY [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   [16]
RP   X-RAY CRYSTALLOGRAPHY.
RG   Joint center for structural genomics (JCSG);
RT   "Crystal structure of ubiquitin carboxyl-terminal hydrolase 6 (yfr010w)
RT   from saccharomyces cerevisiae at 1.74 a resolution.";
RL   Submitted (JUL-2009) to the PDB data bank.
CC   -!- FUNCTION: Predominant proteasome-associated deubiquitinase which
CC       releases ubiquitin from the proteasome targeted ubiquitinated proteins.
CC       Ensures the regeneration of ubiquitin at the proteasome. Has
CC       proteasome-inhibitory activity and delays the degradation of
CC       ubiquitinated proteins to provide a time window allowing gradual
CC       deubiquitination of the substrate. Stabilizes the association of HUL5
CC       with proteasomes and works in opposition to polyubiquitin elongation
CC       activity of HUL5. {ECO:0000269|PubMed:10527495,
CC       ECO:0000269|PubMed:12408819, ECO:0000269|PubMed:14581483,
CC       ECO:0000269|PubMed:17018280, ECO:0000269|PubMed:17190603,
CC       ECO:0000269|PubMed:9344467}.
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: Activated by its association with the proteasome.
CC       {ECO:0000269|PubMed:12408819}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       pH dependence:
CC         Optimum pH is 8.5-9. {ECO:0000269|PubMed:9344467};
CC   -!- SUBUNIT: Associates with the regulatory particle (RP) of the
CC       proteasome.
CC   -!- DOMAIN: The N-terminal ubiquitin-like domain is required for proteasome
CC       association and UBP6 activation at the proteasome.
CC       {ECO:0000269|PubMed:10386876, ECO:0000269|PubMed:12408819}.
CC   -!- MISCELLANEOUS: Present with 6770 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the peptidase C19 family. USP14/UBP6 subfamily.
CC       {ECO:0000305}.
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DR   EMBL; D50617; BAA09249.1; -; Genomic_DNA.
DR   EMBL; BK006940; DAA12450.1; -; Genomic_DNA.
DR   PIR; S56265; S56265.
DR   RefSeq; NP_116665.1; NM_001179975.1.
DR   PDB; 1VJV; X-ray; 1.74 A; A=97-499.
DR   PDB; 5A5B; EM; 9.50 A; 8=97-499.
DR   PDB; 5MPC; EM; 7.70 A; 8=1-499.
DR   PDB; 7QO4; EM; 7.00 A; 8=1-499.
DR   PDB; 7QO5; EM; 6.00 A; 8=1-499.
DR   AlphaFoldDB; P43593; -.
DR   EMDB; EMD-14083; -.
DR   EMDB; EMD-14084; -.
DR   EMDB; EMD-2995; -.
DR   EMDB; EMD-3034; -.
DR   EMDB; EMD-3537; -.
DR   SMR; P43593; -.
DR   BioGRID; 31160; 719.
DR   DIP; DIP-6731N; -.
DR   FunCoup; P43593; 1317.
DR   IntAct; P43593; 81.
DR   STRING; 4932.YFR010W; -.
DR   MEROPS; C19.079; -.
DR   MoonProt; P43593; -.
DR   iPTMnet; P43593; -.
DR   PaxDb; 4932-YFR010W; -.
DR   PeptideAtlas; P43593; -.
DR   EnsemblFungi; YFR010W_mRNA; YFR010W; YFR010W.
DR   GeneID; 850562; -.
DR   KEGG; sce:YFR010W; -.
DR   AGR; SGD:S000001906; -.
DR   SGD; S000001906; UBP6.
DR   VEuPathDB; FungiDB:YFR010W; -.
DR   eggNOG; KOG1872; Eukaryota.
DR   HOGENOM; CLU_017549_2_1_1; -.
DR   InParanoid; P43593; -.
DR   OMA; AAEWWTD; -.
DR   OrthoDB; 333239at2759; -.
DR   BioCyc; YEAST:G3O-30463-MONOMER; -.
DR   Reactome; R-SCE-5689880; Ub-specific processing proteases.
DR   BioGRID-ORCS; 850562; 5 hits in 10 CRISPR screens.
DR   CD-CODE; E03F929F; Stress granule.
DR   EvolutionaryTrace; P43593; -.
DR   PRO; PR:P43593; -.
DR   Proteomes; UP000002311; Chromosome VI.
DR   RNAct; P43593; protein.
DR   GO; GO:0000502; C:proteasome complex; IDA:SGD.
DR   GO; GO:0005838; C:proteasome regulatory particle; IDA:SGD.
DR   GO; GO:0004843; F:cysteine-type deubiquitinase activity; IDA:SGD.
DR   GO; GO:0070628; F:proteasome binding; IBA:GO_Central.
DR   GO; GO:0072671; P:mitochondria-associated ubiquitin-dependent protein catabolic process; IMP:SGD.
DR   GO; GO:1904293; P:negative regulation of ERAD pathway; IBA:GO_Central.
DR   GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; IMP:SGD.
DR   GO; GO:0016579; P:protein deubiquitination; IMP:SGD.
DR   GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:CACAO.
DR   CDD; cd02657; Peptidase_C19A; 1.
DR   FunFam; 3.90.70.10:FF:000156; UBP6p Ubiquitin-specific protease; 1.
DR   Gene3D; 6.10.140.1140; -; 1.
DR   Gene3D; 3.90.70.10; Cysteine proteinases; 1.
DR   Gene3D; 3.10.20.90; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 1; 1.
DR   InterPro; IPR038765; Papain-like_cys_pep_sf.
DR   InterPro; IPR001394; Peptidase_C19_UCH.
DR   InterPro; IPR000626; Ubiquitin-like_dom.
DR   InterPro; IPR029071; Ubiquitin-like_domsf.
DR   InterPro; IPR044635; UBP14-like.
DR   InterPro; IPR028889; USP.
DR   InterPro; IPR018200; USP_CS.
DR   PANTHER; PTHR43982; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE; 1.
DR   PANTHER; PTHR43982:SF1; UBIQUITIN CARBOXYL-TERMINAL HYDROLASE 14; 1.
DR   Pfam; PF00443; UCH; 1.
DR   SMART; SM00213; UBQ; 1.
DR   SUPFAM; SSF54001; Cysteine proteinases; 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 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   3D-structure; Hydrolase; Phosphoprotein; Protease; Reference proteome;
KW   Thiol protease; Ubl conjugation pathway.
FT   CHAIN           1..499
FT                   /note="Ubiquitin carboxyl-terminal hydrolase 6"
FT                   /id="PRO_0000080591"
FT   DOMAIN          6..80
FT                   /note="Ubiquitin-like"
FT   DOMAIN          109..497
FT                   /note="USP"
FT   REGION          365..391
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        365..374
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        118
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   ACT_SITE        447
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT                   ECO:0000255|PROSITE-ProRule:PRU10093"
FT   MOD_RES         389
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   MOD_RES         470
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   HELIX           105..108
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           118..129
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           131..138
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           142..144
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           154..172
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           182..191
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           193..196
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           210..225
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           227..230
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   TURN            231..233
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          235..243
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          246..253
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          257..259
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          261..263
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           272..280
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          297..305
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          307..314
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          317..320
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   TURN            321..324
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          325..328
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          337..340
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           342..344
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           347..369
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           390..413
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          426..442
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          445..453
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          461..465
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          468..472
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           474..478
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   HELIX           479..481
FT                   /evidence="ECO:0007829|PDB:1VJV"
FT   STRAND          488..496
FT                   /evidence="ECO:0007829|PDB:1VJV"
SQ   SEQUENCE   499 AA;  57111 MW;  DAE54D1F8AC9960C CRC64;
     MSGETFEFNI RHSGKVYPIT LSTDATSADL KSKAEELTQV PSARQKYMVK GGLSGEESIK
     IYPLIKPGST VMLLGTPDAN LISKPAKKNN FIEDLAPEQQ VQQFAQLPVG FKNMGNTCYL
     NATLQALYRV NDLRDMILNY NPSQGVSNSG AQDEEIHKQI VIEMKRCFEN LQNKSFKSVL
     PIVLLNTLRK CYPQFAERDS QGGFYKQQDA EELFTQLFHS MSIVFGDKFS EDFRIQFKTT
     IKDTANDNDI TVKENESDSK LQCHISGTTN FMRNGLLEGL NEKIEKRSDL TGANSIYSVE
     KKISRLPKFL TVQYVRFFWK RSTNKKSKIL RKVVFPFQLD VADMLTPEYA AEKVKVRDEL
     RKVEKEKNEK EREIKRRKFD PSSSENVMTP REQYETQVAL NESEKDQWLE EYKKHFPPNL
     EKGENPSCVY NLIGVITHQG ANSESGHYQA FIRDELDENK WYKFNDDKVS VVEKEKIESL
     AGGGESDSAL ILMYKGFGL
//