USP7 - Ubiquitin carboxyl-terminal hydrolase 7 - human protein (Function)
 
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USP7 »  Ubiquitin carboxyl-terminal hydrolase 7   [ EC 3.4.19.12 ]
 
Protein also known as:  Herpesvirus-associated ubiquitin-specific protease.
Gene name:  USP7
Family name: Peptidase C19
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
13
  • CuratedUniProtKB
GO molecular function 
Cysteine-type endopeptidase activitydefinition[GO:0004197]  
1
  • IMPUniProtKB
P53 bindingdefinition[GO:0002039]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
19
  • IPIIntAct
  • IPIUniProtKB
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • IPIUniProtKB
Transcription factor bindingdefinition[GO:0008134]  
1
  • IPIUniProtKB
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
2
  • IPIUniProtKB
Ubiquitin thiolesterase activitydefinition[GO:0004221]  
2
  • IDAUniProtKB
Ubiquitin-specific protease activitydefinition[GO:0004843]  
3
  • IDAUniProtKB
GO biological process 
Maintenance of DNA methylationdefinition[GO:0010216]  
1
  • IMPUniProtKB
Multicellular organismal developmentdefinition[GO:0007275]  
  • IEAUniProtKB KW
Negative regulation of NF-kappaB transcription factor activitydefinition[GO:0032088]  
1
  • IDAUniProtKB
Protein deubiquitinationdefinition[GO:0016579]  
3
  • IDAUniProtKB
Regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051090]  
1
  • IDAUniProtKB
Transcription-coupled nucleotide-excision repairdefinition[GO:0006283]  
1
  • IMPUniProtKB
Ubiquitin-dependent protein catabolic processdefinition[GO:0006511] silver  
  • IEAInterPro 2 GO
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.4.19.12: 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).  
  • CuratedUniProtKB
It is regulated in the following manner
Inhibited by N-ethyl-maleimide (NEM) and divalent cations. Tolerates high concentrations of NaCl but is inhibited at concentrations of 195 mM and higher.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathway:
Herpes simplex infection  hsa05168+7874  
 

Biophysicochemical properties

Dependence
pH Active from pH 7.0 to 9.5.

Keywords

Biological process 
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Host-virus interaction  definition   [KW-0945]
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Developmental protein  definition   [KW-0217]
Hydrolase  definition   [KW-0378]
Protease  definition   [KW-0645]
Thiol protease  definition   [KW-0788]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: USP7
GenomeRNAi: 7874
PRO: PR:Q93009