Ubiquitin carboxyl-terminal hydrolase 12 (USP12)
The protein contains 370 amino acids for an estimated molecular weight of 42858 Da.
Deubiquitinating enzyme. Has almost no deubiquitinating activity by itself and requires the interaction with WDR20 and WDR48 to have a high activity (PubMed:19075014, PubMed:27373336). Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014). In complex with WDR48, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
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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No binding partner found
The reference OMIM entry for this protein is 603091
Ubiquitin-specific protease 12; usp12
Ubiquitin-hydrolyzing enzyme 1; ubh1
DESCRIPTION
In eukaryotic cells, the covalent attachment of ubiquitin (191339) to proteins plays a role in a variety of cellular processes. In many cases, ubiquitination leads to protein degradation by the 26S proteasome. Protein ubiquitination is reversible, and the removal of ubiquitin is catalyzed by deubiquitinating enzymes, or DUBs. Members of one DUB subfamily, the ubiquitin-specific proteases, or UBPs (EC 3.1.2.15), have been identified in a variety of organisms. UBPs are specialized thiol proteases that cleave ubiquitin from several types of substrates. USP12 belongs to the UBP subfamily (summary by Hansen-Hagge et al., 1998).CLONING
While analyzing the breakpoint sequences in a leukemia patient exhibiting the translocation t(5;14)(q33-q34;q11), Hansen-Hagge et al. (1998) identified an intronless pseudogene. By screening a fetal liver cDNA library with the pseudogene, the authors identified a homologous gene that they designated UBH1. The predicted 355-amino acid UBH1 protein contains 2 potential nuclear localization signals as well as the cys, his, and QQD boxes characteristic of UBPs. Northern blot analysis revealed that UBH1 was expressed as a 4.6-kb mRNA in various cell lines. Using Southern hybridization, Hansen-Hagge et al. (1998) determined that UBH1 is highly conserved among vertebrates and is part of a multigene family. The authors cloned mouse Ubh1 cDNA and, by Northern blot analysis and in situ hybridization, found that Ubh1 was expressed in all mouse tissues tested. Strong expression was observed in peripheral ganglia, retina, olfactory epithelium, and distinct areas of the gut.GENE FUNCTION
Hansen-Hagge et al. (1998) found that recombinant human UBH1 expressed in E. coli had deubiquitinating activity. Burska et al. (2013) found that knockdown of USP12 via small interfering RNA resulted in destabilization of androgen receptor (AR; 313700) in human prostate cancer cell lines, decreasing AR transcriptional activity. Silencing of USP12 also decreased the ability of cells to form colonies and increased apoptosis. Mutation analysis revealed that cys48 in the USP12 catalytic domain was required for AR stabilization and that wildtype, but not cys48-mutant USP12, deubiquitinated AR. Cotransfection experiments revealed that USP12 required UAF1 (WDR48; 612167) for its enzymatic activity and AR stabilization. USP12 interacted directly with UAF1 and colocalized with AR in the cytoplasm of steroid-depleted cells.MAPPING
By fluorescence in situ hybridization, Hansen-Hagge et al. (1998) mapped both the human UBH1 gene and pseudogene to chromosome 5q34. ... More on the omim web site
July 1, 2020: Protein entry updated
Automatic update: OMIM entry 603091 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).