FunctionHydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148). 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, preventing degradation of p53/TP53, and enhances p53/TP53-dependent transcription regulation, cell growth repression and apoptosis (PubMed:25283148). 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 (PubMed:21745816). Exhibits a preference towards 'Lys-48'-linked ubiquitin chains. Increases regulatory T-cells (Treg) suppressive capacity by deubiquitinating and stabilizing the transcription factor FOXP3 which is crucial for Treg cell function (PubMed:23973222).
Tissue specificityWidely expressed. Overexpressed in prostate cancer.
Sequence similaritiesBelongs to the peptidase C19 family. Contains 1 MATH domain. Contains 1 USP domain.
DomainThe C-terminus plays a role in its oligomerization.
Post-translational modificationsIsoform 1: Phosphorylated. Isoform 1 is phosphorylated at positions Ser-18 and Ser-963. Isoform 2: Not phosphorylated. Isoform 1: Polyneddylated. Isoform 2: Not Polyneddylated. Isoform 1 and isoform 2: Not sumoylated. Isoform 1 and isoform 2: Polyubiquitinated by herpesvirus 1 trans-acting transcriptional protein ICP0/VMW110; leading to its subsequent proteasomal degradation. Isoform 1: Ubiquitinated at Lys-869.
Cellular localizationNucleus. 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 and PTEN in promyelocytic leukemia protein (PML) nuclear bodies.
Flow Cytometry analysis of HeLa (human cervix adenocarcinoma) cells labeling HAUSP / USP7 with unpurified ab108931 at 1:30 dilution(10ug/ml) (red). Cells were fixed with 80% methanol and permeabilised with 0.1% Tween-20. A Goat anti rabbit IgG (Alexa Fluor® 488)(ab150077)(1:2000 dilution) was used as the secondary antibody. Rabbit monoclonal IgG (Black)(ab172730) was used as the isotype control, Cell without incubation with primary antibody and secondary antibody (Blue) were used as the unlabeled control.
Western blot - Anti-HAUSP / USP7 antibody [EPR4253] (ab108931)
Predicted band size : 128 kDa
Lane 1: Wild-type HAP1 cell lysate (20 µg) Lane 2: HAUSP/USP7 knockout HAP1 cell lysate (20 µg) Lane 3: HeLa cell lysate (20 µg) Lane 4: MCF7 cell lysate (20 µg) Lanes 1 - 4: Merged signal (red and green). Green - ab108931 observed at 115 kDa. Red - loading control, ab8245, observed at 37 kDa.
ab108931 was shown to specifically react with HAUSP/USP7 when HAUSP/USP7 knockout samples were used. Wild-type and HAUSP/USP7 knockout samples were subjected to SDS-PAGE. ab108931 and ab8245 (loading control to GAPDH) were diluted 1/1000 and 1/2000 respectively and incubated overnight at 4°C. Blots were developed with Goat anti-Rabbit IgG H&L (IRDye® 800CW) preadsorbed (ab216773) and Goat anti-Mouse IgG H&L (IRDye® 680RD) preadsorbed (ab216776) secondary antibodies at 1/10 000 dilution for 1 h at room temperature before imaging.
Western blot - HAUSP / USP7 antibody [EPR4253] (ab108931)
All lanes : Anti-HAUSP / USP7 antibody [EPR4253] (ab108931) at 1/1000 dilution
Lane 1 : Ramos cell lysate Lane 2 : HeLa cell lysate Lane 3 : A431 cell lysate Lane 4 : MCF7 cell lysate Lane 5 : C6 cell lysate Lane 6 : RAW 264.7 cell lysate