P50102 (UBP8_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ubiquitin carboxyl-terminal hydrolase 8
EC=3.4.19.12

Alternative name(s):
Deubiquitinating enzyme 8
Ubiquitin thioesterase 8
Ubiquitin-specific-processing protease 8

Gene names

Name:	UBP8
Ordered Locus Names:	YMR223W
ORF Names:	YM9959.05

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	471 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Functions as histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complexes SAGA and SLIK. SAGA is involved in RNA polymerase II-dependent transcriptional regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus. Together with SGF11, is required for histone H2B deubiquitination. Ref.3 Ref.6 Ref.7
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).
Subunit structure	Component of the 1.8 MDa SAGA complex, which consists of at least of TRA1, CHD1, SPT7, TAF5, ADA3, SGF73, SPT20/ADA5, SPT8, TAF12, TAF6, HFI1/ADA1, UBP8, GCN5, ADA2, SPT3, SGF29, TAF10, TAF9, SGF11 and SUS1. TAF5, TAF6, TAF9, TAF19, TAF12 and ADA1 seem to be present in 2 copies. SAGA is built of 5 distinct domains with specialized functions. Domain I (containing TRA1) probably represents the activator interaction surface. Domain II (containing TAF5 and TAF6, and probably TAF9 and TAF10), domain III (containing GCN5, TAF10, SPT7, TAF5 and ADA1, and probably ADA2, ADA3 and TAF12), and domain IV (containing HFI1/ADA1 and TAF6, and probably TAF9) are believed to play primarily an architectural role. Domain III also harbors the HAT activity. Domain V (containing SPT3 and SPT20, and probably SPT8) represents the TBP-interacting module, which may be associated transiently with SAGA. UBP8 interacts with SGF11. Component of the SLIK complex, which consists of at least TRA1, CHD1, SPT7, TAF5, ADA3, SPT20, RTG2, TAF12, TAF6, HFI1, UBP8, GCN5, ADA2, SPT3, TAF10 and TAF9. Ref.4 Ref.6 Ref.7 Ref.8
Subcellular location	Nucleus Probable.
Domain	The UBP-type zinc finger domain is required for the interaction with the SAGA complex.
Miscellaneous	Present with 1030 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the peptidase C19 family. UBP8 subfamily. Contains 1 UBP-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Ubl conjugation pathway
Cellular component	Nucleus
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Protease Thiol protease
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	histone H3-K4 methylation Inferred from mutant phenotype PubMed 16855026. Source: SGD histone H3-K79 methylation Inferred from mutant phenotype PubMed 16855026. Source: SGD histone deubiquitination Inferred from mutant phenotype PubMed 14563679. Source: SGD regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	DUBm complex Inferred from direct assay PubMed 20395473. Source: SGD SAGA complex Inferred from direct assay PubMed 12052880PubMed 14563679. Source: SGD SLIK (SAGA-like) complex Inferred from direct assay PubMed 14563679. Source: SGD
Molecular_function	protein complex scaffold Inferred from mutant phenotype PubMed 20434206. Source: SGD ubiquitin thiolesterase activity Inferred from electronic annotation. Source: InterPro ubiquitin-specific protease activity Inferred from mutant phenotype PubMed 14563679. Source: SGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 471

471

Ubiquitin carboxyl-terminal hydrolase 8

PRO_0000080593

Regions

Zinc finger

44 – 105

62

UBP-type

Sites

Active site

146

1

Nucleophile

Active site

427

1

Proton acceptor By similarity

Experimental info

Mutagenesis

46

1

C → A: Lowers histone H2B deubiquitination activity; when associated with A-49. Ref.7

Mutagenesis

49

1

C → A: Lowers histone H2B deubiquitination activity; when associated with A-46. Ref.7

Mutagenesis

77

1

H → A: Lowers histone H2B deubiquitination activity. Ref.7

Mutagenesis

146

1

C → S: Lowers histone H2B deubiquitination activity. Ref.7

Mutagenesis

419

1

H → A: Lowers histone H2B deubiquitination activity. Ref.7

Secondary structure

1

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471

Helix Strand Turn

Details...

Helix

5 – 10

6

Helix

14 – 32

19

Helix

36 – 43

8

Turn

47 – 49

3

Beta strand

54 – 64

11

Beta strand

66 – 68

3

Turn

69 – 72

4

Helix

73 – 81

9

Beta strand

85 – 88

4

Turn

89 – 91

3

Beta strand

94 – 96

3

Turn

97 – 100

4

Beta strand

101 – 103

3

Helix

107 – 110

4

Helix

112 – 117

6

Helix

118 – 124

7

Helix

130 – 132

3

Beta strand

142 – 144

3

Helix

146 – 156

11

Helix

159 – 166

8

Helix

169 – 173

5

Turn

179 – 181

3

Helix

183 – 195

13

Helix

214 – 226

13

Helix

228 – 230

3

Beta strand

231 – 234

4

Helix

238 – 256

19

Helix

260 – 267

8

Helix

274 – 278

5

Beta strand

281 – 288

8

Turn

290 – 292

3

Beta strand

297 – 304

8

Beta strand

306 – 308

3

Helix

316 – 324

9

Beta strand

327 – 329

3

Turn

337 – 340

4

Beta strand

341 – 343

3

Beta strand

346 – 354

9

Beta strand

356 – 362

7

Beta strand

365 – 367

3

Beta strand

369 – 371

3

Beta strand

373 – 375

3

Beta strand

384 – 387

4

Helix

389 – 391

3

Beta strand

409 – 422

14

Beta strand

425 – 433

9

Turn

435 – 437

3

Beta strand

439 – 443

5

Beta strand

446 – 450

5

Helix

452 – 455

4

Beta strand

460 – 470

11

Sequences

	Sequence		Length	Mass (Da)
	P50102 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: BC632F12FBD0F73C	FASTA	471	53,623
	10 20 30 40 50 60 MSICPHIQQV FQNEKSKDGV LKTCNAARYI LNHSVPKEKF LNTMKCGTCH EINSGATFMC 70 80 90 100 110 120 LQCGFCGCWN HSHFLSHSKQ IGHIFGINSN NGLLFCFKCE DYIGNIDLIN DAILAKYWDD 130 140 150 160 170 180 VCTKTMVPSM ERRDGLSGLI NMGSTCFMSS ILQCLIHNPY FIRHSMSQIH SNNCKVRSPD 190 200 210 220 230 240 KCFSCALDKI VHELYGALNT KQASSSSTST NRQTGFIYLL TCAWKINQNL AGYSQQDAHE 250 260 270 280 290 300 FWQFIINQIH QSYVLDLPNA KEVSRANNKQ CECIVHTVFE GSLESSIVCP GCQNNSKTTI 310 320 330 340 350 360 DPFLDLSLDI KDKKKLYECL DSFHKKEQLK DFNYHCGECN STQDAIKQLG IHKLPSVLVL 370 380 390 400 410 420 QLKRFEHLLN GSNRKLDDFI EFPTYLNMKN YCSTKEKDKH SENGKVPDII YELIGIVSHK 430 440 450 460 470 GTVNEGHYIA FCKISGGQWF KFNDSMVSSI SQEEVLKEQA YLLFYTIRQV N

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII." Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T., Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K., Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P. , Skelton J., Walsh S.V., Whitehead S., Barrell B.G. Nature 387:90-93(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"Expanded lysine acetylation specificity of Gcn5 in native complexes." Grant P.A., Eberharter A., John S., Cook R.G., Turner B.M., Workman J.L. J. Biol. Chem. 274:5895-5900(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HISTONE ACETYLATION AT THE SAGA COMPLEX.
[4]	"The novel SLIK histone acetyltransferase complex functions in the yeast retrograde response pathway." Pray-Grant M.G., Schieltz D., McMahon S.J., Wood J.M., Kennedy E.L., Cook R.G., Workman J.L., Yates J.R. III, Grant P.A. Mol. Cell. Biol. 22:8774-8786(2002) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE SLIK COMPLEX.
[5]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[6]	"Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription." Daniel J.A., Torok M.S., Sun Z.W., Schieltz D., Allis C.D., Yates J.R. III, Grant P.A. J. Biol. Chem. 279:1867-1871(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HISTONE DEUBIQUITINATION ACTIVITY OF THE SAGA COMPLEX, IDENTIFICATION IN THE SAGA COMPLEX, IDENTIFICATION IN THE SLIK COMPLEX.
[7]	"H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex." Ingvarsdottir K., Krogan N.J., Emre N.C.T., Wyce A., Thompson N.J., Emili A., Hughes T.R., Greenblatt J.F., Berger S.L. Mol. Cell. Biol. 25:1162-1172(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN HISTONE DEUBIQUITINATION ACTIVITY OF THE SAGA COMPLEX, IDENTIFICATION IN THE SAGA COMPLEX, INTERACTION WITH SGF11, MUTAGENESIS OF CYS-46; CYS-49; HIS-77; CYS-146 AND HIS-419.
[8]	"Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation." Pray-Grant M.G., Daniel J.A., Schieltz D., Yates J.R. III, Grant P.A. Nature 433:434-438(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE SLIK COMPLEX.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z49939 Genomic DNA. Translation: CAA90194.1.
BK006946 Genomic DNA. Translation: DAA10122.1.

PIR

S57591.

RefSeq

NP_013950.1. NM_001182730.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3M99	X-ray	2.70	A	1-471	[»]
3MHH	X-ray	2.45	A	1-471	[»]
3MHS	X-ray	1.89	A	1-471	[»]
4FIP	X-ray	2.69	A/E	1-471	[»]
4FJC	X-ray	2.83	A/E	1-471	[»]
4FK5	X-ray	2.03	A	1-471	[»]

ProteinModelPortal

P50102.

SMR

P50102. Positions 1-471.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1506N.

IntAct

P50102. 165 interactions.

MINT

MINT-393758.

STRING

4932.YMR223W.

Protein family/group databases

MEROPS

C19.087.

Proteomic databases

PaxDb

P50102.

PeptideAtlas

P50102.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YMR223W; YMR223W; YMR223W.

GeneID

855263.

KEGG

sce:YMR223W.

Organism-specific databases

CYGD

YMR223w.

SGD

S000004836. UBP8.

Phylogenomic databases

eggNOG

COG5533.

GeneTree

ENSGT00690000101718.

HOGENOM

HOG000216626.

KO

K11366.

OMA

KANEDWS.

OrthoDB

EOG4X3M8J.

Enzyme and pathway databases

BioCyc

YEAST:G3O-32904-MONOMER.

Gene expression databases

Genevestigator

P50102.

GermOnline

YMR223W. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]

Pfam

PF00443. UCH. 1 hit.
PF02148. zf-UBP. 1 hit.
[Graphical view]

SMART

SM00290. ZnF_UBP. 1 hit.
[Graphical view]

PROSITE

PS00972. UCH_2_1. 1 hit.
PS00973. UCH_2_2. 1 hit.
PS50235. UCH_2_3. 1 hit.
PS50271. ZF_UBP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P50102.

NextBio

978861.

Entry information

Entry name

UBP8_YEAST

Accession

Primary (citable) accession number: P50102
Secondary accession number(s): D6W048

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program