Reviewed, UniProtKB/Swiss-Prot P40818 (UBP8_HUMAN)

Names and origin

Protein names

Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 8
    EC=3.1.2.15
Alternative name(s):
    Ubiquitin thioesterase 8
    Ubiquitin-specific-processing protease 8
    Deubiquitinating enzyme 8
      Short name=hUBPy

Gene names

Name:	USP8
Synonyms:	KIAA0055, UBPY

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1118 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Involved in cell proliferation. Probably regulates the stability of STAM2 and RASGRF1. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and STAM2. Ref.4
Catalytic activity	Ubiquitin C-terminal thioester + H2O = ubiquitin + a thiol.
Subunit structure	Forms a ternary complex with RNF128 and OTUB1. Interacts (via C-terminal UCH catalytic domain) with OTUB1 isoform 1. Interacts with STAM2 (via SH3 domain). Interacts with RASGRF1 and RNF41. Interacts with IST1. Ref.8
Induction	Upon growth stimulation in starved human fibroblasts. Decreases in response to growth arrest induced by cell-cell contact. Ref.4
Sequence similarities	Belongs to the peptidase C19 family. Contains 1 rhodanese domain.
Sequence caution	The sequence AAH38801.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence AAH51345.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Coding sequence diversity	Polymorphism
Domain	SH3-binding
Molecular function	Hydrolase Protease Thiol protease
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell proliferation Ref.4 Traceable author statement. Source: ProtInc ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from direct assay. Source: HPA
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW cysteine-type endopeptidase activity Traceable author statement. Source: ProtInc ubiquitin thiolesterase activity Inferred from electronic annotation. Source: EC ubiquitin-specific protease activity Ref.4 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHMP1A	Q9HD42	2	EBI-1050865,EBI-1057156
CHMP1B	Q7LBR1	2	EBI-1050865,EBI-2118090
CHMP4C	Q96CF2	1	EBI-1050865,EBI-1221015
YWHAB	P31946	1	EBI-1050865,EBI-359815
YWHAQ	P27348	1	EBI-1050865,EBI-359854
YWHAZ	P63104	1	EBI-1050865,EBI-347088

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1118

1118

Ubiquitin carboxyl-terminal hydrolase 8

PRO_0000080627

Regions

Domain

195 – 313

119

Rhodanese

Motif

405 – 413

9

SH3-binding By similarity

Sites

Active site

786

1

By similarity

Active site

1059

1

By similarity

Active site

1067

1

By similarity

Amino acid modifications

Modified residue

434

1

Phosphoserine Ref.5

Modified residue

452

1

Phosphoserine Ref.6

Modified residue

718

1

Phosphoserine Ref.6

Modified residue

719

1

Phosphoserine Ref.6

Natural variations

Natural variant

443

1

D → G: dbSNP rs3743044.

VAR_017796

Natural variant

739

1

T → A: dbSNP rs11638390.

VAR_051525

Natural variant

827

1

A → G: dbSNP rs1056577.

VAR_017797

Experimental info

Sequence conflict

526

1

E → G in CAD97662. Ref.2

Sequence conflict

717

1

Y → H in CAD97662. Ref.2

Sequence conflict

945

1

T → A in CAD97662. Ref.2

Secondary structure

1

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1118

Helix Strand Turn

Details...

Helix

17 – 21

5

Helix

22 – 24

3

Helix

28 – 30

3

Helix

33 – 52

20

Helix

56 – 73

18

Helix

77 – 81

5

Helix

83 – 90

8

Helix

92 – 138

47

Beta strand

181 – 183

3

Helix

185 – 192

8

Beta strand

195 – 197

3

Beta strand

199 – 205

7

Helix

207 – 212

6

Beta strand

219 – 221

3

Beta strand

223 – 225

3

Helix

232 – 237

6

Helix

243 – 248

6

Helix

249 – 251

3

Beta strand

253 – 259

7

Helix

265 – 267

3

Helix

273 – 279

7

Turn

280 – 284

5

Beta strand

295 – 299

5

Helix

301 – 307

7

Helix

309 – 311

3

Helix

763 – 765

3

Beta strand

782 – 784

3

Helix

786 – 796

11

Helix

799 – 806

8

Turn

807 – 809

3

Helix

810 – 813

4

Helix

825 – 839

15

Beta strand

842 – 845

4

Helix

848 – 857

10

Helix

859 – 861

3

Beta strand

862 – 865

4

Helix

869 – 884

16

Helix

903 – 917

15

Helix

921 – 926

6

Beta strand

928 – 936

9

Turn

937 – 939

3

Beta strand

942 – 954

13

Beta strand

959 – 963

5

Helix

964 – 971

8

Beta strand

975 – 977

3

Beta strand

983 – 985

3

Turn

986 – 989

4

Beta strand

990 – 992

3

Beta strand

994 – 1002

9

Beta strand

1005 – 1011

7

Beta strand

1014 – 1016

3

Beta strand

1018 – 1023

6

Beta strand

1027 – 1029

3

Helix

1038 – 1040

3

Beta strand

1051 – 1061

11

Turn

1063 – 1065

3

Beta strand

1067 – 1074

8

Turn

1075 – 1078

4

Beta strand

1079 – 1084

6

Beta strand

1087 – 1090

4

Helix

1093 – 1095

3

Beta strand

1101 – 1107

7

Sequences

	Sequence		Length	Mass (Da)
	P40818-1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 8B884B7A842F9A9A	FASTA	1,118	127,523
	10 20 30 40 50 60 MPAVASVPKE LYLSSSLKDL NKKTEVKPEK ISTKSYVHSA LKIFKTAEEC RLDRDEERAY 70 80 90 100 110 120 VLYMKYVTVY NLIKKRPDFK QQQDYFHSIL GPGNIKKAVE EAERLSESLK LRYEEAEVRK 130 140 150 160 170 180 KLEEKDRQEE AQRLQQKRQE TGREDGGTLA KGSLENVLDS KDKTQKSNGE KNEKCETKEK 190 200 210 220 230 240 GAITAKELYT MMTDKNISLI IMDARRMQDY QDSCILHSLS VPEEAISPGV TASWIEAHLP 250 260 270 280 290 300 DDSKDTWKKR GNVEYVVLLD WFSSAKDLQI GTTLRSLKDA LFKWESKTVL RNEPLVLEGG 310 320 330 340 350 360 YENWLLCYPQ YTTNAKVTPP PRRQNEEVSI SLDFTYPSLE ESIPSKPAAQ TPPASIEVDE 370 380 390 400 410 420 NIELISGQNE RMGPLNISTP VEPVAASKSD VSPIIQPVPS IKNVPQIDRT KKPAVKLPEE 430 440 450 460 470 480 HRIKSESTNH EQQSPQSGKV IPDRSTKPVV FSPTLMLTDE EKARIHAETA LLMEKNKQEK 490 500 510 520 530 540 ELRERQQEEQ KEKLRKEEQE QKAKKKQEAE ENEITEKQQK AKEEMEKKES EQAKKEDKET 550 560 570 580 590 600 SAKRGKEITG VKRQSKSEHE TSDAKKSVED RGKRCPTPEI QKKSTGDVPH TSVTGDSGSG 610 620 630 640 650 660 KPFKIKGQPE SGILRTGTFR EDTDDTERNK AQREPLTRAR SEEMGRIVPG LPSGWAKFLD 670 680 690 700 710 720 PITGTFRYYH SPTNTVHMYP PEMAPSSAPP STPPTHKAKP QIPAERDREP SKLKRSYSSP 730 740 750 760 770 780 DITQAIQEEE KRKPTVTPTV NRENKPTCYP KAEISRLSAS QIRNLNPVFG GSGPALTGLR 790 800 810 820 830 840 NLGNTCYMNS ILQCLCNAPH LADYFNRNCY QDDINRSNLL GHKGEVAEEF GIIMKALWTG 850 860 870 880 890 900 QYRYISPKDF KITIGKINDQ FAGYSQQDSQ ELLLFLMDGL HEDLNKADNR KRYKEENNDH 910 920 930 940 950 960 LDDFKAAEHA WQKHKQLNES IIVALFQGQF KSTVQCLTCH KKSRTFEAFM YLSLPLASTS 970 980 990 1000 1010 1020 KCTLQDCLRL FSKEEKLTDN NRFYCSHCRA RRDSLKKIEI WKLPPVLLVH LKRFSYDGRW 1030 1040 1050 1060 1070 1080 KQKLQTSVDF PLENLDLSQY VIGPKNNLKK YNLFSVSNHY GGLDGGHYTA YCKNAARQRW 1090 1100 1110 FKFDDHEVSD ISVSSVKSSA AYILFYTSLG PRVTDVAT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1." Nomura N., Nagase T., Miyajima N., Sazuka T., Tanaka A., Sato S., Seki N., Kawarabayasi Y., Ishikawa K., Tabata S. DNA Res. 1:223-229(1994) [PubMed: 7584044] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung and Lymph.
[4]	"UBPY: a growth-regulated human ubiquitin isopeptidase." Naviglio S., Mattecucci C., Matoskova B., Nagase T., Nomura N., Di Fiore P.P., Draetta G.F. EMBO J. 17:3241-3250(1998) [PubMed: 9628861] [Abstract] Cited for: FUNCTION, INDUCTION.
[5]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-434, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-452; SER-718 AND SER-719, MASS SPECTROMETRY.
[7]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]	"Essential role of hIST1 in cytokinesis." Agromayor M., Carlton J.G., Phelan J.P., Matthews D.R., Carlin L.M., Ameer-Beg S., Bowers K., Martin-Serrano J. Mol. Biol. Cell 20:1374-1387(2009) [PubMed: 19129480] [Abstract] Cited for: INTERACTION WITH IST1.
[9]	"Solution structure of the rhodanese-like domain in human ubiquitin specific protease 8 (ubp8)." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 174-317.
[10]	"Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8)." Avvakumov G.V., Walker J.R., Xue S., Finerty P.J. Jr., Mackenzie F., Newman E.M., Dhe-Paganon S. J. Biol. Chem. 281:38061-38070(2006) [PubMed: 17035239] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-318 IN COMPLEX WITH RNF41.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

D29956 mRNA. Translation: BAA06225.2.
BX537420 mRNA. Translation: CAD97662.1.
BC038801 mRNA. Translation: AAH38801.1. Sequence problems.
BC051345 mRNA. Translation: AAH51345.1. Sequence problems.
BC110590 mRNA. Translation: AAI10591.1.

IPI

IPI00030915.

RefSeq

NP_001122082.1.
NP_001122083.1.
NP_005145.3.

UniGene

Hs.644563

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WHB	NMR	-	A	176-317	[»]
2A9U	X-ray	2.10	A/B	1-142	[»]
2GFO	X-ray	2.00	A	734-1110	[»]
2GWF	X-ray	2.30	A/C/E	181-318	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P40818. 8 interactions.

Protein family/group databases

MEROPS

C19.011.

PTM databases

PhosphoSite

P40818.

Proteomic databases

PeptideAtlas

P40818.

PRIDE

P40818.

Genome annotation databases

Ensembl

ENSG00000138592. Homo sapiens. [Contig view]

GeneID

9101.

KEGG

hsa:9101.

Organism-specific databases

GeneCards

GC15P048503.

H-InvDB

HIX0012234.

HGNC

HGNC:12631. USP8.

HPA

HPA004869.

MIM

603158. gene.

PharmGKB

PA27531.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P40818.

HOVERGEN

P40818.

OMA

P40818. FTYPSLE.

Enzyme and pathway databases

BRENDA

3.1.2.15. 247.

Gene expression databases

ArrayExpress

P40818.

Bgee

P40818.

CleanEx

HS_USP8.

GermOnline

ENSG00000138592. Homo sapiens.

Family and domain databases

InterPro

IPR015063. DUF1873.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19.
IPR001763. Rhodanese-like.
[Graphical view]

Gene3D

G3DSA:3.40.250.10. Rhodanese-like. 1 hit.

Pfam

PF08969. DUF1873. 1 hit.
PF00581. Rhodanese. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view]

SMART

SM00450. RHOD. 1 hit.
[Graphical view]

PROSITE

PS50206. RHODANESE_3. 1 hit.
PS00972. UCH_2_1. 1 hit.
PS00973. UCH_2_2. 1 hit.
PS50235. UCH_2_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

34117.

SOURCE

Search...

Entry information

Entry name

UBP8_HUMAN

Accession

Primary (citable) accession number: P40818
Secondary accession number(s): Q2TB31 , Q7Z3U2, Q86VA0, Q8IWI7

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	June 16, 2009
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)