InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: USP7

Summary

InnateDB Protein

IDBP-13960.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

USP7

Protein Name

ubiquitin specific peptidase 7 (herpes virus-associated)

Synonyms

HAUSP; TEF1;

Species

Homo sapiens

Ensembl Protein

ENSP00000343535

InnateDB Gene

IDBG-13958 (USP7)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11923872, ECO:0000269PubMed:14506283, ECO:0000269PubMed:15053880, ECO:0000269PubMed:16160161, ECO:0000269PubMed:16964248, ECO:0000269PubMed:18590780, ECO:0000269PubMed:18716620, ECO:0000269PubMed:20153724, ECO:0000269PubMed:21745816, ECO:0000269PubMed:22411829, ECO:0000269PubMed:22466611, ECO:0000269PubMed:22466612, ECO:0000269PubMed:22689415}.

Subcellular Localization

Nucleus. Cytoplasm. Nucleus, PML body. Note=Present in a minority of ND10 nuclear bodies. Association with ICP0/VMW110 at early times of infection leads to an increased proportion of USP7-containing ND10. Colocalizes with ATXN1 in the nucleus. Colocalized with DAXX in speckled structures. Colocalized with PML and PTEN in promyelocytic leukemia protein (PML) nuclear bodies.

Disease Associations

Tissue Specificity

Widely expressed. Overexpressed in prostate cancer. {ECO:0000269PubMed:18716620}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 275 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	275 [view]
Protein-Protein	273 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002039	p53 binding
GO:0004197	cysteine-type endopeptidase activity
GO:0004221	ubiquitin thiolesterase activity
GO:0004843	ubiquitin-specific protease activity
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0008134	transcription factor binding
GO:0008234	cysteine-type peptidase activity
GO:0031625	ubiquitin protein ligase binding
GO:0036459	ubiquitinyl hydrolase activity

Biological Process

GO:0006283	transcription-coupled nucleotide-excision repair
GO:0006511	ubiquitin-dependent protein catabolic process
GO:0007275	multicellular organismal development
GO:0010216	maintenance of DNA methylation
GO:0016032	viral process
GO:0016579	protein deubiquitination
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0045087	innate immune response (InnateDB)
GO:0051090	regulation of sequence-specific DNA binding transcription factor activity

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016605	PML body

Protein Structure and Domains

PDB ID

InterPro

IPR001394 Peptidase C19, ubiquitin carboxyl-terminal hydrolase
IPR002083 MATH
IPR008974 TRAF-like
IPR024729 ICP0-binding domain of Ubiquitin-specific protease 7
IPR028889 Ubiquitin carboxyl-terminal hydrolase-like domain

PFAM

PF00443
PF00917
PF12436

PRINTS

PIRSF

SMART

SM00061

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q93009