UniProt Accession

 UBP7_HUMAN; Q93009; A6NMY8 

Genbank Protein ID

 Z72499; AC022167; CH471112 

Genbank Nucleotide ID

 CAA96580.1; EAW85194.1 

Protein Name

 Ubiquitin carboxyl-terminal hydrolase 7 

Protein Synonyms/Alias

 Deubiquitinating enzyme 7; Herpesvirus-associated ubiquitin-specific protease; Ubiquitin thioesterase 7; Ubiquitin-specific-processing protease 7 

Gene Name

 USP7 

Gene Synonyms/Alias

 HAUSP 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
98	FVRNLPWKIMVMPRF	ubiquitination	[1, 2, 3]
148	INYRDDEKSFSRRIS	ubiquitination	[1, 3]
240	FFTNQLRKAVYMMPT	ubiquitination	[2]
254	TEGDDSSKSVPLALQ	ubiquitination	[2, 4]
272	YELQHSDKPVGTKKL	ubiquitination	[2]
312	DNVENKMKGTCVEGT	ubiquitination	[2]
335	MVSYIQCKEVDYRSD	ubiquitination	[2]
355	YDIQLSIKGKKNIFE	ubiquitination	[1, 3, 4, 5]
420	PQTDQNIKINDRFEF	ubiquitination	[1, 2, 3, 4, 5]
439	PLDEFLQKTDPKDPA	ubiquitination	[4]
476	LNPKGDGKWCKFDDD	ubiquitination	[2, 6]
479	KGDGKWCKFDDDVVS	ubiquitination	[1, 2, 3]
490	DVVSRCTKEEAIEHN	ubiquitination	[2]
523	LVYIRESKLSEVLQA	ubiquitination	[2]
595	KVKYTVFKVLKNSSL	acetylation	[7]
595	KVKYTVFKVLKNSSL	ubiquitination	[2]
681	ATLPKFDKDHDVMLF	ubiquitination	[2]
695	FLKMYDPKTRSLNYC	ubiquitination	[2]
712	IYTPISCKIRDLLPV	ubiquitination	[2]
755	DYDVSLDKALDELMD	ubiquitination	[4]
770	GDIIVFQKDDPENDN	ubiquitination	[4]
824	MNYFQVAKTVAQRLN	ubiquitination	[1, 2, 3, 4, 5]
841	PMLLQFFKSQGYRDG	ubiquitination	[1, 2, 3]
869	RDLLQFFKPRQPKKL	acetylation	[7]
869	RDLLQFFKPRQPKKL	ubiquitination	[1, 2, 3, 4, 5, 6]
875	FKPRQPKKLYYQQLK	ubiquitination	[2, 4]
882	KLYYQQLKMKITDFE	ubiquitination	[1, 2, 3, 5]
914	EITLYPDKHGCVRDL	ubiquitination	[2]
926	RDLLEECKKAVELGE	ubiquitination	[2]
927	DLLEECKKAVELGEK	ubiquitination	[2]
934	KAVELGEKASGKLRL	ubiquitination	[2, 4]
1033	SLLDIQEKEFEKFKF	ubiquitination	[1, 2, 3]
1039	EKEFEKFKFAIVMMG	ubiquitination	[2]
1084	LGLDHFNKAPKRSRY	acetylation	[7]
1096	SRYTYLEKAIKIHN*	acetylation	[7]
1096	SRYTYLEKAIKIHN*	ubiquitination	[1, 2, 3, 4, 5, 6]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 

Functional Description

 Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX. Together with DAXX, prevents MDM2 self-ubiquitination and enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination and proteasomal degradation. Deubiquitinates p53/TP53 and MDM2 and strongly stabilizes p53/TP53 even in the presence of excess MDM2, and also induces p53/TP53- dependent cell growth repression and apoptosis. Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity. In association with DAXX, is involved in the deubiquitination and translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML. Involved in cell proliferation during early embryonic development. Involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage: recruited to DNA damage sites following interaction with KIAA1530/UVSSA and promotes deubiquitination of ERCC6, preventing UV-induced degradation of ERCC6. Contributes to the overall stabilization and trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection. Involved in maintenance of DNA methylation via its interaction with UHRF1 and DNMT1: acts by mediating deubiquitination of UHRF1 and DNMT1, preventing their degradation and promoting DNA methylation by DNMT1. Exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. 

Sequence Annotation

 DOMAIN 68 195 MATH.
 REGION 1 208 Interaction with TSPYL5.
 REGION 53 208 Interaction with p53/TP53, MDM2 and
 REGION 70 205 Necessary for nuclear localization.
 REGION 622 801 Interaction with ICP0/VMW110.
 ACT_SITE 223 223 Nucleophile.
 ACT_SITE 464 464 Proton acceptor (Probable).
 MOD_RES 18 18 Phosphoserine.
 MOD_RES 869 869 N6-acetyllysine; alternate.
 MOD_RES 963 963 Phosphoserine.
 MOD_RES 1084 1084 N6-acetyllysine.
 MOD_RES 1096 1096 N6-acetyllysine.
 CROSSLNK 869 869 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Acetylation; Alternative splicing; Complete proteome; Cytoplasm; Developmental protein; Direct protein sequencing; DNA damage; DNA repair; Host-virus interaction; Hydrolase; Isopeptide bond; Nucleus; Phosphoprotein; Protease; Reference proteome; Thiol protease; Ubl conjugation; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1102 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0004197; F:cysteine-type endopeptidase activity; IMP:UniProtKB.
 GO:0002039; F:p53 binding; IDA:UniProtKB.
 GO:0004221; F:ubiquitin thiolesterase activity; IDA:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; IDA:UniProtKB.
 GO:0010216; P:maintenance of DNA methylation; IMP:UniProtKB.
 GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
 GO:0016579; P:protein deubiquitination; IDA:UniProtKB.
 GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:InterPro.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 

Interpro

 IPR002083; MATH.
 IPR024729; Pept_C19_dom.
 IPR018200; Pept_C19ubi-hydrolase_C_CS.
 IPR001394; Peptidase_C19.
 IPR008974; TRAF-like. 

Pfam

 PF00917; MATH
 PF00443; UCH
 PF12436; USP7 

SMART

 SM00061; MATH 

PROSITE

 PS50144; MATH
 PS00972; UCH_2_1
 PS00973; UCH_2_2
 PS50235; UCH_2_3 

PRINTS