[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), TISSUE SPECIFICITY, AND VARIANTS ARG-475 AND GLN-912. TISSUE=Ewing sarcoma; PubMed=1565468 [NCBI, ExPASy, EBI, Israel, Japan] Nakamura T., Hillova J., Mariage-Samson R., Onno M., Huebner K., Cannizzaro L.A., Boghosian-Sell L., Croce C.M., Hill M.; "A novel transcriptional unit of the tre oncogene widely expressed in human cancer cells."; Oncogene 7:733-741(1992).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, AND DISCUSSION OF TRE2 EVOLUTION. DOI=10.1073/pnas.0437015100; PubMed=12604796 [NCBI, ExPASy, EBI, Israel, Japan] Paulding C.A., Ruvolo M., Haber D.A.; "The Tre2 (USP6) oncogene is a hominoid-specific gene."; Proc. Natl. Acad. Sci. U.S.A. 100:2507-2511(2003).
[3]	CHARACTERIZATION. DOI=10.1038/366313a0; PubMed=8247125 [NCBI, ExPASy, EBI, Israel, Japan] Papa F.R., Hochstrasser M.; "The yeast DOA4 gene encodes a deubiquitinating enzyme related to a product of the human tre-2 oncogene."; Nature 366:313-319(1993).
[4]	MUTAGENESIS OF THR-150 AND ARG-187. DOI=10.1016/j.bbrc.2003.09.051; PubMed=14521938 [NCBI, ExPASy, EBI, Israel, Japan] Bizimungu C., De Neve N., Burny A., Bach S., Bontemps F., Portetelle D., Vandenbol M.; "Expression in a RabGAP yeast mutant of two human homologues, one of which is an oncogene."; Biochem. Biophys. Res. Commun. 310:498-504(2003).

Comments

FUNCTION: Has an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity.
CATALYTIC ACTIVITY: Ubiquitin C-terminal thioester + H₂O = ubiquitin + a thiol.
INTERACTION:
Q8N8A2:ANKRD44; NbExp=2; IntAct=EBI-954590, EBI-1245329;
P10916:MYL2; NbExp=2; IntAct=EBI-954590, EBI-725770;

ALTERNATIVE PRODUCTS: 3 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	P35125-1
This is the isoform sequence displayed in this entry.

Name	2
Synonyms	213(ORF2)
Isoform ID	P35125-2
Features which should be applied to build the isoform sequence: VSP_010878, VSP_010879.

Name	3
Synonyms	210(ORF1), oncTre210p
Isoform ID	P35125-3
Note: Was shown to be tumorigenic in transfected mice and seems not to act as GTPase activating protein.
Features which should be applied to build the isoform sequence: VSP_010880, VSP_010881.

TISSUE SPECIFICITY: Testis specific. Expressed in various cancer cell lines.
DISEASE: Involved in tumorigenesis.
MISCELLANEOUS: The USP6 gene only exists in the primate lineage.
SIMILARITY: Belongs to the peptidase C19 family [view classification].
SIMILARITY: Contains 1 Rab-GAP TBC domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/USP6ID530ch17p13.html";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X63546; CAA45108.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X63547; CAA45111.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY143550; AAN38838.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY163314; AAO21348.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI

IPI00423562; -.
IPI00423563; -.
IPI00423565; -.

PIR

S57867; S57867.
S57868; S22158.
S57874; S22155.

RefSeq

NP_004496.2; -.

UniGene

Hs.448851

3D structure databases

ModBase

P35125.

Protein-protein interaction databases

IntAct

P35125; 4.

Protein family/group databases

MEROPS

C19.009; -.

PTM databases

PhosphoSite

P35125; -.

Enzyme and pathway databases

BRENDA

3.1.2.15; 247.

Pathway_Interaction_DB

arf6cyclingpathway; Arf6 signaling events.

Organism-specific databases

GeneCards

GC17P004972; -.

H-InvDB

HIX0005679; -.
HIX0021760; -.

HGNC:12629; USP6.

604334; gene. [NCBI / EBI]

PharmGKB

PA27529; -.

Gene expression databases

P35125; -.

P35125; -.

HS_USP6; -.

ENSG00000129204; Homo sapiens.

Ontologies

GO:0005764;	Cellular component: lysosome (traceable author statement from ProtInc).
GO:0004197;	Molecular function: cysteine-type endopeptidase activity (traceable author statement from UniProtKB).
GO:0003676;	Molecular function: nucleic acid binding (traceable author statement from ProtInc).
GO:0005515;	Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0005097;	Molecular function: Rab GTPase activator activity (inferred from electronic annotation from InterPro).
GO:0004221;	Molecular function: ubiquitin thiolesterase activity (inferred from electronic annotation from EC).
GO:0006464;	Biological process: protein modification process (non-traceable author statement from UniProtKB).
GO:0032313;	Biological process: regulation of Rab GTPase activity (inferred from electronic annotation from InterPro).
GO:0006511;	Biological process: ubiquitin-dependent protein catabolic process (inferred from electronic annotation from InterPro).
QuickGo view.

Family and domain databases

InterPro

IPR018200; Pept_C19ubi-hydrolase_C_CS.
IPR001394; Peptidase_C19.
IPR000195; RabGAP_TBC.
Graphical view of domain structure.

Pfam

PF00566; TBC; 1.
PF00443; UCH; 1.
Pfam graphical view of domain structure.

SMART

SM00164; TBC; 1.
SMART graphical view of domain structure.

PROSITE

PS50086; TBC_RABGAP; 1.
PS00972; UCH_2_1; 1.
PS00973; UCH_2_2; 1.
PS50235; UCH_2_3; 1.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

P35125; -.

Genome annotation databases

Ensembl

ENSG00000129204; Homo sapiens. [Contig view]

GeneID

9098; -.

KEGG

hsa:9098; -.

Phylogenomic databases

HOGENOM

P35125; -.

HOVERGEN

P35125; -.

OMA

P35125; SCAWCPQ.

Other

34099; -.

USP6; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Alternative splicing; Hydrolase; Polymorphism; Protease; Proto-oncogene; Thiol protease; Ubl conjugation pathway.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 1406`	`1406`	`Ubiquitin carboxyl-terminal hydrolase 6.`	`PRO_0000080625`
`DOMAIN`	`100 292`	`193`	`Rab-GAP TBC.`
`ACT_SITE`	`541 541`		`By similarity.`
`ACT_SITE`	`1320 1320`		`By similarity.`
`ACT_SITE`	`1328 1328`		`By similarity.`
`VAR_SEQ`	`1 317`		`Missing (in isoform 2).`	`VSP_010878`
`VAR_SEQ`	`318 359`		`GLWARLRNQFFDTWAMNDDTVLKHLRASTKKLTRKQG` `DLPPP -> MPQRLPHARQHTPLPLGSADYRRVVSVRPQGPHRDPK` `DSRDA (in isoform 2).`	`VSP_010879`
`VAR_SEQ`	`774 786`		`NFPQDNQKVQLSV -> ISPLHHLQMECSP (in isoform 3).`	`VSP_010880`
`VAR_SEQ`	`787 1406`		`Missing (in isoform 3).`	`VSP_010881`
`VARIANT`	`475 475`	`1`	`W -> R (in dbSNP:rs8073787 [NCBI]).`	`VAR_051522`
`VARIANT`	`912 912`	`1`	`R -> Q (in dbSNP:rs9899177 [NCBI]).`	`VAR_051523`
`VARIANT`	`1330 1330`	`1`	`I -> V (in dbSNP:rs1053611 [NCBI]).`	`VAR_051524`
`MUTAGEN`	`150 150`		`T->R: Does not restore GAP activity in yeast complementation assay.`
`MUTAGEN`	`187 187`		`R->Q: Does not restore GAP activity in yeast complementation assay.`
`CONFLICT`	`963 963`		`N -> I (in Ref. 1; CAA45111).`

Sequence information

Length: 1406 AA [This is the length of the unprocessed precursor]

Molecular weight: 158658 Da [This is the MW of the unprocessed precursor]

CRC64: D3A6822CEB441DB3 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MDMVENADSL QAQERKDILM KYDKGHRAGL PEDKGPEPVG INSSIDRFGI LHETELPPVT 

        70         80         90        100        110        120 
AREAKKIRRE MTRTSKWMEM LGEWETYKHS SKLIDRVYKG IPMNIRGPVW SVLLNIQEIK 

       130        140        150        160        170        180 
LKNPGRYQIM KERGKRSSEH IHHIDLDVRT TLRNHVFFRD RYGAKQRELF YILLAYSEYN 

       190        200        210        220        230        240 
PEVGYCRDLS HITALFLLYL PEEDAFWALV QLLASERHSL PGFHSPNGGT VQGLQDQQEH 

       250        260        270        280        290        300 
VVPKSQPKTM WHQDKEGLCG QCASLGCLLR NLIDGISLGL TLRLWDVYLV EGEQVLMPIT 

       310        320        330        340        350        360 
SIALKVQQKR LMKTSRCGLW ARLRNQFFDT WAMNDDTVLK HLRASTKKLT RKQGDLPPPA 

       370        380        390        400        410        420 
KREQGSLAPR PVPASRGGKT LCKGYRQAPP GPPAQFQRPI CSASPPWASR FSTPCPGGAV 

       430        440        450        460        470        480 
REDTYPVGTQ GVPSLALAQG GPQGSWRFLE WKSMPRLPTD LDIGGPWFPH YDFEWSCWVR 

       490        500        510        520        530        540 
AISQEDQLAT CWQAEHCGEV HNKDMSWPEE MSFTANSSKI DRQKVPTEKG ATGLSNLGNT 

       550        560        570        580        590        600 
CFMNSSIQCV SNTQPLTQYF ISGRHLYELN RTNPIGMKGH MAKCYGDLVQ ELWSGTQKSV 

       610        620        630        640        650        660 
APLKLRRTIA KYAPKFDGFQ QQDSQELLAF LLDGLHEDLN RVHEKPYVEL KDSDGRPDWE 

       670        680        690        700        710        720 
VAAEAWDNHL RRNRSIIVDL FHGQLRSQVK CKTCGHISVR FDPFNFLSLP LPMDSYMDLE 

       730        740        750        760        770        780 
ITVIKLDGTT PVRYGLRLNM DEKYTGLKKQ LRDLCGLNSE QILLAEVHDS NIKNFPQDNQ 

       790        800        810        820        830        840 
KVQLSVSGFL CAFEIPVPSS PISASSPTQI DFSSSPSTNG MFTLTTNGDL PKPIFIPNGM 

       850        860        870        880        890        900 
PNTVVPCGTE KNFTNGMVNG HMPSLPDSPF TGYIIAVHRK MMRTELYFLS PQENRPSLFG 

       910        920        930        940        950        960 
MPLIVPCTVH TRKKDLYDAV WIQVSWLARP LPPQEASIHA QDRDNCMGYQ YPFTLRVVQK 

       970        980        990       1000       1010       1020 
DGNSCAWCPQ YRFCRGCKID CGEDRAFIGN AYIAVDWHPT ALHLRYQTSQ ERVVDKHESV 

      1030       1040       1050       1060       1070       1080 
EQSRRAQAEP INLDSCLRAF TSEEELGESE MYYCSKCKTH CLATKKLDLW RLPPFLIIHL 

      1090       1100       1110       1120       1130       1140 
KRFQFVNDQW IKSQKIVRFL RESFDPSAFL VPRDPALCQH KPLTPQGDEL SKPRILAREV 

      1150       1160       1170       1180       1190       1200 
KKVDAQSSAG KEDMLLSKSP SSLSANISSS PKGSPSSSRK SGTSCPSSKN SSPNSSPRTL 

      1210       1220       1230       1240       1250       1260 
GRSKGRLRLP QIGSKNKPSS SKKNLDASKE NGAGQICELA DALSRGHMRG GSQPELVTPQ 

      1270       1280       1290       1300       1310       1320 
DHEVALANGF LYEHEACGNG CGDGYSNGQL GNHSEEDSTD DQREDTHIKP IYNLYAISCH 

      1330       1340       1350       1360       1370       1380 
SGILSGGHYI TYAKNPNCKW YCYNDSSCEE LHPDEIDTDS AYILFYEQQG IDYAQFLPKI 

      1390       1400 
DGKKMADTSS TDEDSESDYE KYSMLQ

P35125 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools