Ubiquitin carboxyl-terminal hydrolase 7 (USP7)
The protein contains 1102 amino acids for an estimated molecular weight of 128302 Da.
Hydrolase that deubiquitinates target proteins such as FOXO4, p53/TP53, MDM2, ERCC6, DNMT1, UHRF1, PTEN, KMT2E/MLL5 and DAXX (PubMed:11923872, PubMed:15053880, PubMed:16964248, PubMed:18716620, PubMed:25283148, PubMed:26678539, PubMed:28655758). 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 (PubMed:15053880, PubMed:16845383, PubMed:18566590, PubMed:20153724). 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 (PubMed:11923872). Deubiquitination of FOXO4 in presence of hydrogen peroxide is not dependent on p53/TP53 and inhibits FOXO4-induced transcriptional activity (PubMed:16964248). 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 (PubMed:18716620). Deubiquitinates KMT2E/MLL5 preventing KMT2E/MLL5 proteasomal-mediated degradation (PubMed:26678539). 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 (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Histone deubiquitination
Histone H2B conserved C-terminal lysine deubiquitination
Maintenance of DNA methylation
Monoubiquitinated protein deubiquitination
Multicellular organism development
Negative regulation of NF-kappaB transcription factor activity
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of DNA demethylation
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Protein K63-linked deubiquitination
Protein stabilization
Protein ubiquitination
Regulation of circadian rhythm
Regulation of DNA-binding transcription factor activity
Regulation of gluconeogenesis
Regulation of proteasomal protein catabolic process
Regulation of protein stability
Regulation of retrograde transport, endosome to Golgi
Regulation of signal transduction by p53 class mediator
Regulation of telomere capping
Rhythmic process
Transcription-coupled nucleotide-excision repair
Ubiquitin-dependent protein catabolic process
Viral process
Cellular Component
Chromosome
Cytosol
Nuclear body
Nucleoplasm
Nucleus
PML body
Protein complex
Protein-containing complex
The reference OMIM entry for this protein is 602519
Ubiquitin-specific protease 7; usp7
Ubiquitin-specific protease, herpesvirus-associated
Herpesvirus-associated ubiquitin-specific protease; hausp
Vmw110-associated protein, 135-kd
CLONING
Herpes simplex virus type 1 (HSV-1) immediate-early protein Vmw110 is a nonspecific activator of gene expression and is required for efficient initiation of the viral lytic cycle. Vmw110 has been shown to bind to PML (102578)-containing nuclear bodies (ND10) and a 135-kD cellular protein. By screening a HeLa cell cDNA library with oligonucleotides based on the amino acid sequence of the purified 135-kD protein, Everett et al. (1997) cloned a cDNA encoding Vmw110-associated 135-kD protein, called herpesvirus-associated ubiquitin-specific protease (HAUSP) by them. The 1,102-amino acid HAUSP protein contains the 2 highly conserved active site domains of ubiquitin-specific proteases (USPs), a polyglutamine tract near the N terminus, and several regions predicted to form alpha helices. The authors showed that HAUSP can cleave model substrates of USPs. By immunofluorescence, they found that HAUSP is a predominantly nuclear protein that is present in a minority of ND10. Expression of Vmw110 early in virus infection increases the proportion of ND10 that contain HAUSP. Everett et al. (1997) stated that these results implicate a novel ubiquitin-dependent pathway in both the function of ND10 and the control of viral gene expression. Northern blot analysis of HeLa cell poly(A)+ RNA detected 2 low-level transcripts, 1 approximately 4.5 kb and the other slightly larger and of lower abundance. The NCBI dbEST database contains expressed sequence tags that match the HAUSP sequence and are derived from brain, liver, placenta, lung, and melanocyte cDNA libraries, suggesting that HAUSP is expressed in a wide variety of cell types. Zapata et al. (2001) identified an N-terminal TRAF (see 601711)-like domain in USP7. USP7 localized predominantly to the nucleus in transfected COS-7 cells, and localization required the TRAF-like domain. In USP7, Holowaty et al. (2003) identified an N-terminal p53 (191170)-binding domain, a catalytic domain, and 2 C-terminal domains. The p53-binding domain is identical to the TRAF-like domain described by Zapata et al. (2001).GENE FUNCTION
By mass spectrometry of affinity-purified p53-associated factors, Li et al. (2002) identified HAUSP as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess MDM2 (164785), and also induces p53-dependent cell growth repression and apoptosis. HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vivo and in vitro. Expression of a catalytically inactive point mutation of HAUSP in cells increased the levels of p53 ubiquitination and also destabilized p53. Li et al. (2002) concluded that their findings revealed an important mechanism by which p53 can be stabilized by direct deubiquitination and also implied that HAUSP may function as a tumor suppressor in vivo through the stabilization of p53. Zapata et al. (2001) found that the TRAF-like domain of USP7 could interact in vitro with all TRAF proteins tested. The TRAF-like domain also suppressed NFKB (see 164011) induction by TRAF2 (601895), TRAF6 (602355), and some TRAF-binding TNF receptors (see 191190). Holowaty et al. (2003) determined that in vitro translated USP7 could hydrolyze a linear ubiquitin fusion protein. Biochemical characterization indicated that deubiquitination by USP7 was resistant to high salt concentrations and high pH, but it was inactivated by a thiol-blocking reagent. USP7 also removed ubiquitin from a high molecular mass p ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602519 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed