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ubiquitin carboxyl-terminal hydrolase 7; deubiquitinating enzyme 7; Herpesvirus-associated ubiquitin-specific protease; ubiquitin thioesterase 7; ubiquitin-specific-processing protease 7 (USP7, HAUSP)

Function: - deubiquitinates target proteins including FOXO4, p53/TP53, MDM2, PTEN & DAXX - together with DAXX, prevents MDM2 self-ubiquitination & enhances the E3 ligase activity of MDM2 towards p53/TP53, thereby promoting p53/TP53 ubiquitination & proteasomal degradation - deubiquitinates p53/TP53 & MDM2 & strongly stabilizes p53/TP53 even in the presence of excess MDM2, & also induces p53/TP53-dependent cell growth repression & apoptosis - deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 & inhibits FOXO4-induced transcriptional activity - in association with DAXX, is involved in deubiquitination & translocation of PTEN from the nucleus to the cytoplasm, both processes that are counteracted by PML - involved in cell proliferation during early embryonic development - contributes to the overall stabilization & trans-activation capability of the herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 during HSV-1 infection - thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin - isoform 1 - phosphorylated at positions Ser-18 & Ser-963 - polyneddylated - ubiquitinated at Lys-869 - isoform 2: not phosphorylated, not polyneddylated - isoforms 1 & 2: - not sumoylated - polyubiquitinated by herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110; leading to subsequent proteasomal degradation. isoform 1: - part of a complex with DAXX, MDM2, RASSF1 & USP7 - part of a complex with DAXX, MDM2 & USP7 - interacts with MDM2; the interaction is independent of p53/TP53 - interacts with DAXX; the interaction is direct & independent of MDM2 & p53/TP53 - interacts with FOXO4; the interaction is enhanced in presence of hydrogen peroxide & occurs independently of p53/TP53 - interacts with p53/TP53; the interaction is enhanced in response to DNA damage; the interaction is impaired by TSPYL5 - interacts with PTEN; the interaction is direct - interacts with UBXN6 - interacts with ATXN1; the strength of interaction is influenced by the length of the poly-Gln region in ATXN1; weaker interaction seen with mutants having longer poly-Gln regions - isoforms 1 & 2 interact with herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110 - interacts with epstein-Barr virus EBNA1 - EBNA1 shows a 10-fold higher affinity than p53/TP53 & can compete with it for USP7 binding - binding to ICP0/VMW110 may modulate the substrate specificity or activity of USP7 to stabilize viral proteins Kinetic parameters: - tolerates high concentrations of NaCl but is inhibited at concentrations of 195 mM & higher - pH dependence: active from pH 7.0 to 9.5 Inhibition: - inhibited by N-ethyl-maleimide & divalent cations Structure: - monomer, homodimer - the C-terminus plays a role in its oligomerization - belongs to the peptidase C19 family - contains 1 MATH domain Compartment: - cytoplasm, nucleus, PML body - 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 & PTEN in PML nuclear bodies Alternative splicing: named isoforms=2 Expression: - widely expressed Pathology: - overexpressed in prostate cancer

Related

ubiquitin (UBCEP2, UBB, UBC)

General

nuclear protein phosphoprotein ubiquitin C-terminal hydrolase; UCH; ubiquitin thiolesterase; ubiquitin-specific processing protease; deubiquitinating enzyme

Properties

SIZE: entity length = 1102 aa MW = 128 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: TSPYL5 interaction {1-208} MOTIF: glutamine-rich region {4-10} MOTIF: glutamine residue (SEVERAL) Ser phosphorylation site {S18} Ser phosphorylation site {S49} p53/MDM2/EBNA1 interaction {53-208} Thr phosphorylation site {T54} MATH {68-195} nuclear translocation signal {70-205} cysteine residue {C223} histidine residue {H464} ICP0/VMW110 interaction {622-801} Ser phosphorylation site {S963}

Database Correlations

OMIM 602519 UniProt Q93009 PFAM correlations Entrez Gene 7874 Kegg hsa:7874 ENZYME 3.4.19.12

References

  1. UniProt :accession Q93009
  2. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org//genes/USP7ID42773ch16p13.html
  3. OMIM :accession 602519