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

More general terms

• ubiquitin C-terminal hydrolase
• nuclear protein
• phosphoprotein

Additional terms

• ubiquitin (UBCEP2, UBB, UBC)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7874
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7874
• OMIM: https://mirror.omim.org/entry/602519
• UniProt: http://www.uniprot.org/uniprot/Q93009.html