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FLASH GENE
Symbol USP7 contributors: mct/shn - updated : 06-11-2016
HGNC name ubiquitin specific protease 7 (herpes virus-associated)
HGNC id 12630
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a MATH domain
  • a p53 binding domain
  • a catalytic domain,
  • two C-terminal domains
  • an N-terminal TRAF-like domain
  • mono polymer dimer
    HOMOLOGY
    interspecies ortholog to Usp7, Rattus norvegicus
    ortholog to USP7, Pan troglodytes
    ortholog to usp7, Danio rerio
    ortholog to Usp7, Mus musculus
    Homologene
    FAMILY
  • deubiquitin peptidase family C19
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm,nuclear bodies
    text interacting with MARCH7 in the nucleus
    basic FUNCTION
  • ubiquitin-specific protease, stimulating viral gene expression
  • playing a role in the pathogenesis of spinocerebellar ataxia type 1
  • deubiquitylating enzyme playing a role not only in transcriptional regulation but also in DNA replication, apoptosis, and possibly endosomal organization
  • has an important role in regulating FOXO-mediated stress responses
  • can stabilize MARCH7, and deubiquitylate MARCH7 in the nucleus
  • deubiquitinase that critically regulates the TP53-MDM2 pathway and modulates the TP53 function, inducing TP53-dependent cell growth repression and apoptosis
  • USP7 is a deubiquitinating enzyme that regulates the ubiquitination state of RNF2
  • stabilizes REST through deubiquitylation and antagonizes beta-TrCP in regulating REST at the post-translational level
  • counterbalances REST ubiquitylation and prevents neural stem/progenitor cells (NPCs) differentiation, and USP7-mediated deubiquitylation represents a critical regulatory mechanism involved in the maintenance of NPCs
  • involved in the cellular stress response by regulating MDM2 and TP53 protein levels following severe DNA damage
  • stimulates repair of oxidative DNA lesions
  • has a critical role in regulating the TP53-MDM2 (murine double minute 2) pathway
  • USP7-mediated TP53 regulation is crucial for brain development
  • dual role of USP7, regulating the protein turnover of UHRF1 and stimulating the enzymatic activity of DNMT1
  • regulates the stability of TP53 and the TP53-binding protein MDM2
  • plays a major role in regulating genome stability and cancer prevention by controlling the key proteins involved in the DNA damage response
  • its regulation plays a central role in DNA damage signal transmission
  • UVSSA, together with USP7, is implicated in regulating
  • Transcription-coupled nucleotide excision repair (TC-NER) activity
  • NMRAL1 and USP7 function in concert in inhibiting polyubiquination of IKBKG, thus inhibiting NFKB activity
  • is a protein deubiquitinase with an essential role in development
  • USP7 may act as an oncogenic protein that can modulate MYC expression via TRRAP
  • is a novel component of the cellular DDR involved in preserving the genome stability
  • TRIM32 associates with the deubiquitination enzyme USP7, which previously has been implicated in neural stem cell maintenance, and exhibit a dynamic and partially overlapping expression pattern during neuronal differentiation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • SCML2/USP7 complex constitutes a novel molecular pathway in modulating the epigenetic state of sex chromosomes during male meiosis
  • a component
  • transitory constituent of discrete nuclear structures (ND10)
  • part of USP7-HLTF-PCNA molecular network controlling DNA damage response
  • complexing with TRIM27 and ubiquitination-deubiquitination cascade mediated by the TRIM27-USP7 complex plays an important role in TNF-induced apoptosis
  • INTERACTION
    DNA
    RNA
    small molecule
  • polyubiquitinated, polyneddylated, and dimerized
  • protein
  • binding herpes virus type 1 immediate early protein Vmw 110
  • p53
  • ataxin 1, SCA1
  • guanine monphosphate synthetase, GMPS
  • EBNA1 peptide
  • a key regulator of p53 and Mdm2
  • Mdm4 p53 binding protein homolog (mouse), MDM4
  • forkhead box O4, FOXO4
  • checkpoint with forkhead and ring finger domains, CHFR
  • Claspin, CLSPN
  • Polycomb repressive complex 1, PRC1; melanoma nuclear protein 18, MEL18; BMI1 polycomb ring finger oncogene, BMI1
  • TSPYL5 interacts with USP7(TSPYL5 reduces the activity of USP7 towards TP53, resulting in increased TP53 ubiquitylation)
  • both DNMT1 and UHRF1 coprecipitate with ubiquitin specific peptidase 7 (USP7)
  • ING1 physically interacts with herpesvirus-associated ubiquitin-specific protease (USP7)
  • interaction partner of DNMT1 and UHRF1
  • is a novel regulator of HLTF stability
  • USP7 interacts with UHRF1 (both physical interaction and catalytic activity of USP7 are necessary for UHRF1 ubiquitylation and stability regulation)
  • UVSSA-USP7–mediated stabilization of ERCC6 represents a critical regulatory mechanism of TC-NER in restoring gene expression
  • UVSSA forms a complex with USP7, stabilizes ERCC6 and restores the hypophosphorylated form of RNA polymerase II after UV irradiation
  • USP7 is a novel interacting protein of the oligonucleotide/oligosaccharide-binding fold of TPP1, which was previously known to recruit telomerase to telomeres
  • RNF220 interacts with USP7, a ubiquitin-specific peptidase, which is required for RNF220 to stabilize CTNNB1
  • UHRF1 and USP7 are two new interaction partners for MBD4
  • USP7 cooperates with SCML2 to regulate the activity of PRC1
  • TRRAP physically interact and co-localize with USP7
  • de-ubiquitylating enzyme USP7 is a critical regulator of RAD18 protein levels
  • KMT2E protein stability is cooperatively regulated by O-GlcNAc transferase (OGT) and ubiquitin-specific protease 7 (USP7)
  • ATF4 could maintain SREBF1 protein stability by directly activating the expression of USP7 which deubiquitinates SREBF1 and increases its protein content in cell
  • balanced ubiquitination and deubiquitination of MYC by TRIM32 and USP7 is a novel mechanism for stem cell fate determination
  • cell & other
    REGULATION
    inhibited by bilateral inhibition of USP7 deubiquitinase by a viral interferon regulatory factor protein
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    therapeutic target for tuning TP53-mediated antitumor activity
    ANIMAL & CELL MODELS
  • neural cell survival and brain development of hausp-mutant mice can largely be restored in the Tp53-null background