UBP6_YEAST
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 03-AUG-2022, entry version 197.
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 (1.74 ANGSTROMS) OF 97-499.
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 it's 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; 7QO5; EM; 6.00 A; 8=1-499.
DR PDBsum; 1VJV; -.
DR PDBsum; 5A5B; -.
DR PDBsum; 5MPC; -.
DR PDBsum; 7QO5; -.
DR AlphaFoldDB; P43593; -.
DR SMR; P43593; -.
DR BioGRID; 31160; 647.
DR DIP; DIP-6731N; -.
DR IntAct; P43593; 25.
DR MINT; P43593; -.
DR STRING; 4932.YFR010W; -.
DR MEROPS; C19.079; -.
DR MoonProt; P43593; -.
DR iPTMnet; P43593; -.
DR MaxQB; P43593; -.
DR PaxDb; P43593; -.
DR PRIDE; P43593; -.
DR EnsemblFungi; YFR010W_mRNA; YFR010W; YFR010W.
DR GeneID; 850562; -.
DR KEGG; sce:YFR010W; -.
DR SGD; S000001906; UBP6.
DR VEuPathDB; FungiDB:YFR010W; -.
DR eggNOG; KOG1872; Eukaryota.
DR GeneTree; ENSGT00940000174573; -.
DR HOGENOM; CLU_017549_2_1_1; -.
DR InParanoid; P43593; -.
DR OMA; RKVQFPF; -.
DR BioCyc; YEAST:G3O-30463-MON; -.
DR Reactome; R-SCE-5689880; Ub-specific processing proteases.
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:1901799; P:negative regulation of proteasomal protein catabolic process; IMP:SGD.
DR GO; GO:0016579; P:protein deubiquitination; IMP:SGD.
DR GO; GO:0061136; P:regulation of proteasomal protein catabolic process; IBA:GO_Central.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:CACAO.
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; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR PANTHER; PTHR43982; PTHR43982; 1.
DR Pfam; PF00443; UCH; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF54236; SSF54236; 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..382
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 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
