UBP8_YEAST
ID UBP8_YEAST Reviewed; 471 AA.
AC P50102; D6W048;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Ubiquitin carboxyl-terminal hydrolase 8;
DE EC=3.4.19.12;
DE AltName: Full=Deubiquitinating enzyme 8;
DE AltName: Full=Ubiquitin thioesterase 8;
DE AltName: Full=Ubiquitin-specific-processing protease 8;
GN Name=UBP8; OrderedLocusNames=YMR223W; ORFNames=YM9959.05;
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 FUNCTION IN HISTONE ACETYLATION AT THE SAGA COMPLEX.
RX PubMed=10026213; DOI=10.1074/jbc.274.9.5895;
RA Grant P.A., Eberharter A., John S., Cook R.G., Turner B.M., Workman J.L.;
RT "Expanded lysine acetylation specificity of Gcn5 in native complexes.";
RL J. Biol. Chem. 274:5895-5900(1999).
RN [4]
RP IDENTIFICATION IN THE SLIK COMPLEX.
RX PubMed=12446794; DOI=10.1128/mcb.22.24.8774-8786.2002;
RA Pray-Grant M.G., Schieltz D., McMahon S.J., Wood J.M., Kennedy E.L.,
RA Cook R.G., Workman J.L., Yates J.R. III, Grant P.A.;
RT "The novel SLIK histone acetyltransferase complex functions in the yeast
RT retrograde response pathway.";
RL Mol. Cell. Biol. 22:8774-8786(2002).
RN [5]
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 [6]
RP FUNCTION IN HISTONE DEUBIQUITINATION ACTIVITY OF THE SAGA COMPLEX,
RP IDENTIFICATION IN THE SAGA COMPLEX, AND IDENTIFICATION IN THE SLIK COMPLEX.
RX PubMed=14660634; DOI=10.1074/jbc.c300494200;
RA Daniel J.A., Torok M.S., Sun Z.W., Schieltz D., Allis C.D., Yates J.R. III,
RA Grant P.A.;
RT "Deubiquitination of histone H2B by a yeast acetyltransferase complex
RT regulates transcription.";
RL J. Biol. Chem. 279:1867-1871(2004).
RN [7]
RP FUNCTION IN HISTONE DEUBIQUITINATION ACTIVITY OF THE SAGA COMPLEX,
RP IDENTIFICATION IN THE SAGA COMPLEX, INTERACTION WITH SGF11, AND MUTAGENESIS
RP OF CYS-46; CYS-49; HIS-77; CYS-146 AND HIS-419.
RX PubMed=15657441; DOI=10.1128/mcb.25.3.1162-1172.2005;
RA Ingvarsdottir K., Krogan N.J., Emre N.C.T., Wyce A., Thompson N.J.,
RA Emili A., Hughes T.R., Greenblatt J.F., Berger S.L.;
RT "H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional
RT module within the Saccharomyces cerevisiae SAGA complex.";
RL Mol. Cell. Biol. 25:1162-1172(2005).
RN [8]
RP IDENTIFICATION IN THE SLIK COMPLEX.
RX PubMed=15647753; DOI=10.1038/nature03242;
RA Pray-Grant M.G., Daniel J.A., Schieltz D., Yates J.R. III, Grant P.A.;
RT "Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-
RT dependent acetylation.";
RL Nature 433:434-438(2005).
CC -!- FUNCTION: Functions as histone deubiquitinating component of the
CC transcription regulatory histone acetylation (HAT) complexes SAGA and
CC SLIK. SAGA is involved in RNA polymerase II-dependent transcriptional
CC regulation of approximately 10% of yeast genes. At the promoters, SAGA
CC is required for recruitment of the basal transcription machinery. It
CC influences RNA polymerase II transcriptional activity through different
CC activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter
CC selectivity, interaction with transcription activators (GCN5, ADA2,
CC ADA3 and TRA1), and chromatin modification through histone acetylation
CC (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone
CC H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA
CC interacts with DNA via upstream activating sequences (UASs). SLIK is
CC proposed to have partly overlapping functions with SAGA. It
CC preferentially acetylates methylated histone H3, at least after
CC activation at the GAL1-10 locus. Together with SGF11, is required for
CC histone H2B deubiquitination. {ECO:0000269|PubMed:10026213,
CC ECO:0000269|PubMed:14660634, ECO:0000269|PubMed:15657441}.
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: Component of the 1.8 MDa SAGA complex, which consists of at
CC least of TRA1, CHD1, SPT7, TAF5, ADA3, SGF73, SPT20/ADA5, SPT8, TAF12,
CC TAF6, HFI1/ADA1, UBP8, GCN5, ADA2, SPT3, SGF29, TAF10, TAF9, SGF11 and
CC SUS1. TAF5, TAF6, TAF9, TAF19, TAF12 and ADA1 seem to be present in 2
CC copies. SAGA is built of 5 distinct domains with specialized functions.
CC Domain I (containing TRA1) probably represents the activator
CC interaction surface. Domain II (containing TAF5 and TAF6, and probably
CC TAF9 and TAF10), domain III (containing GCN5, TAF10, SPT7, TAF5 and
CC ADA1, and probably ADA2, ADA3 and TAF12), and domain IV (containing
CC HFI1/ADA1 and TAF6, and probably TAF9) are believed to play primarily
CC an architectural role. Domain III also harbors the HAT activity. Domain
CC V (containing SPT3 and SPT20, and probably SPT8) represents the TBP-
CC interacting module, which may be associated transiently with SAGA. UBP8
CC interacts with SGF11. Component of the SLIK complex, which consists of
CC at least TRA1, CHD1, SPT7, TAF5, ADA3, SPT20, RTG2, TAF12, TAF6, HFI1,
CC UBP8, GCN5, ADA2, SPT3, TAF10 and TAF9. {ECO:0000269|PubMed:12446794,
CC ECO:0000269|PubMed:14660634, ECO:0000269|PubMed:15647753,
CC ECO:0000269|PubMed:15657441}.
CC -!- INTERACTION:
CC P50102; Q12060: HFI1; NbExp=9; IntAct=EBI-19863, EBI-8287;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- DOMAIN: The UBP-type zinc finger domain is required for the interaction
CC with the SAGA complex.
CC -!- MISCELLANEOUS: Present with 1030 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the peptidase C19 family. UBP8 subfamily.
CC {ECO:0000305}.
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DR EMBL; Z49939; CAA90194.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA10122.1; -; Genomic_DNA.
DR PIR; S57591; S57591.
DR RefSeq; NP_013950.1; NM_001182730.1.
DR PDB; 3M99; X-ray; 2.70 A; A=1-471.
DR PDB; 3MHH; X-ray; 2.45 A; A=1-471.
DR PDB; 3MHS; X-ray; 1.89 A; A=1-471.
DR PDB; 4FIP; X-ray; 2.69 A; A/E=1-471.
DR PDB; 4FJC; X-ray; 2.83 A; A/E=1-471.
DR PDB; 4FK5; X-ray; 2.03 A; A=1-471.
DR PDB; 4WA6; X-ray; 2.36 A; A/D=1-471.
DR PDB; 4ZUX; X-ray; 3.82 A; U/Z/e/j=1-471.
DR PDB; 6AQR; X-ray; 2.10 A; A=1-471.
DR PDB; 6T9L; EM; 3.60 A; K=1-471.
DR PDBsum; 3M99; -.
DR PDBsum; 3MHH; -.
DR PDBsum; 3MHS; -.
DR PDBsum; 4FIP; -.
DR PDBsum; 4FJC; -.
DR PDBsum; 4FK5; -.
DR PDBsum; 4WA6; -.
DR PDBsum; 4ZUX; -.
DR PDBsum; 6AQR; -.
DR PDBsum; 6T9L; -.
DR AlphaFoldDB; P50102; -.
DR SMR; P50102; -.
DR BioGRID; 35401; 467.
DR ComplexPortal; CPX-656; SAGA complex.
DR ComplexPortal; CPX-675; SLIK (SAGA-like) complex.
DR DIP; DIP-1506N; -.
DR IntAct; P50102; 166.
DR MINT; P50102; -.
DR STRING; 4932.YMR223W; -.
DR MEROPS; C19.087; -.
DR MaxQB; P50102; -.
DR PaxDb; P50102; -.
DR PRIDE; P50102; -.
DR EnsemblFungi; YMR223W_mRNA; YMR223W; YMR223W.
DR GeneID; 855263; -.
DR KEGG; sce:YMR223W; -.
DR SGD; S000004836; UBP8.
DR VEuPathDB; FungiDB:YMR223W; -.
DR eggNOG; KOG1867; Eukaryota.
DR GeneTree; ENSGT00940000175497; -.
DR HOGENOM; CLU_008279_11_2_1; -.
DR InParanoid; P50102; -.
DR OMA; FMSVILQ; -.
DR BioCyc; YEAST:G3O-32904-MON; -.
DR Reactome; R-SCE-5689880; Ub-specific processing proteases.
DR EvolutionaryTrace; P50102; -.
DR PRO; PR:P50102; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P50102; protein.
DR GO; GO:0071819; C:DUBm complex; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0000124; C:SAGA complex; IDA:SGD.
DR GO; GO:0046695; C:SLIK (SAGA-like) complex; IDA:SGD.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; IMP:SGD.
DR GO; GO:0060090; F:molecular adaptor activity; IDA:SGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0016573; P:histone acetylation; IDA:ComplexPortal.
DR GO; GO:0016578; P:histone deubiquitination; IMP:SGD.
DR GO; GO:0051568; P:histone H3-K4 methylation; IMP:SGD.
DR GO; GO:0034729; P:histone H3-K79 methylation; IMP:SGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:ComplexPortal.
DR GO; GO:0008380; P:RNA splicing; IMP:SGD.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR001394; Peptidase_C19_UCH.
DR InterPro; IPR037798; UBP8.
DR InterPro; IPR018200; USP_CS.
DR InterPro; IPR028889; USP_dom.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR PANTHER; PTHR21646:SF33; PTHR21646:SF33; 1.
DR Pfam; PF00443; UCH; 1.
DR Pfam; PF02148; zf-UBP; 1.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
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; Hydrolase; Metal-binding; Nucleus; Protease;
KW Reference proteome; Thiol protease; Transcription;
KW Transcription regulation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..471
FT /note="Ubiquitin carboxyl-terminal hydrolase 8"
FT /id="PRO_0000080593"
FT DOMAIN 137..468
FT /note="USP"
FT ZN_FING 22..122
FT /note="UBP-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT ACT_SITE 146
FT /note="Nucleophile"
FT ACT_SITE 427
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10092,
FT ECO:0000255|PROSITE-ProRule:PRU10093"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 49
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 60
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 73
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT BINDING 83
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT MUTAGEN 46
FT /note="C->A: Lowers histone H2B deubiquitination activity;
FT when associated with A-49."
FT /evidence="ECO:0000269|PubMed:15657441"
FT MUTAGEN 49
FT /note="C->A: Lowers histone H2B deubiquitination activity;
FT when associated with A-46."
FT /evidence="ECO:0000269|PubMed:15657441"
FT MUTAGEN 77
FT /note="H->A: Lowers histone H2B deubiquitination activity."
FT /evidence="ECO:0000269|PubMed:15657441"
FT MUTAGEN 146
FT /note="C->S: Lowers histone H2B deubiquitination activity."
FT /evidence="ECO:0000269|PubMed:15657441"
FT MUTAGEN 419
FT /note="H->A: Lowers histone H2B deubiquitination activity."
FT /evidence="ECO:0000269|PubMed:15657441"
FT HELIX 5..10
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 14..32
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 36..43
FT /evidence="ECO:0007829|PDB:3MHS"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 54..64
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:3MHS"
FT TURN 69..72
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 73..81
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:3MHS"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:3MHS"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 107..110
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 112..117
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 118..124
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 146..156
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 159..166
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 169..173
FT /evidence="ECO:0007829|PDB:3MHS"
FT TURN 179..181
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 183..195
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 214..226
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 228..230
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 238..256
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 260..267
FT /evidence="ECO:0007829|PDB:4FK5"
FT HELIX 274..278
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:3MHS"
FT TURN 290..292
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 297..304
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 316..324
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:4FJC"
FT TURN 337..340
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:4FJC"
FT STRAND 346..354
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 356..362
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:3M99"
FT STRAND 373..375
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 384..387
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 389..391
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 409..422
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 425..433
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:6AQR"
FT STRAND 439..443
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 446..450
FT /evidence="ECO:0007829|PDB:3MHS"
FT HELIX 452..455
FT /evidence="ECO:0007829|PDB:3MHS"
FT STRAND 460..470
FT /evidence="ECO:0007829|PDB:3MHS"
SQ SEQUENCE 471 AA; 53623 MW; BC632F12FBD0F73C CRC64;
MSICPHIQQV FQNEKSKDGV LKTCNAARYI LNHSVPKEKF LNTMKCGTCH EINSGATFMC
LQCGFCGCWN HSHFLSHSKQ IGHIFGINSN NGLLFCFKCE DYIGNIDLIN DAILAKYWDD
VCTKTMVPSM ERRDGLSGLI NMGSTCFMSS ILQCLIHNPY FIRHSMSQIH SNNCKVRSPD
KCFSCALDKI VHELYGALNT KQASSSSTST NRQTGFIYLL TCAWKINQNL AGYSQQDAHE
FWQFIINQIH QSYVLDLPNA KEVSRANNKQ CECIVHTVFE GSLESSIVCP GCQNNSKTTI
DPFLDLSLDI KDKKKLYECL DSFHKKEQLK DFNYHCGECN STQDAIKQLG IHKLPSVLVL
QLKRFEHLLN GSNRKLDDFI EFPTYLNMKN YCSTKEKDKH SENGKVPDII YELIGIVSHK
GTVNEGHYIA FCKISGGQWF KFNDSMVSSI SQEEVLKEQA YLLFYTIRQV N
