Ubiquitin carboxyl-terminal hydrolase 47 (USP47)
The protein contains 1375 amino acids for an estimated molecular weight of 157311 Da.
Ubiquitin-specific protease that specifically deubiquitinates monoubiquitinated DNA polymerase beta (POLB), stabilizing POLB thereby playing a role in base-excision repair (BER). Acts as a regulator of cell growth and genome integrity. May also indirectly regulate CDC25A expression at a transcriptional level. (updated: Jan. 31, 2018)
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.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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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| Variant | Description |
|---|---|
| dbSNP:rs11022079 |
Biological Process
Base-excision repair
Cellular response to DNA damage stimulus
Cellular response to UV
Monoubiquitinated protein deubiquitination
Negative regulation of apoptotic process
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
Negative regulation of G2/M transition of mitotic cell cycle
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
Negative regulation of transcription, DNA-templated
Positive regulation of canonical Wnt signaling pathway
Positive regulation of cell growth
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Regulation of proteasomal protein catabolic process
Regulation of protein stability
Response to drug
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 614460
Ubiquitin-specific protease 47; usp47
DESCRIPTION
USP47 belongs to a family of ubiquitin-specific cysteine proteases. These enzymes catalyze the removal of ubiquitin from proteins that are ubiquitinated and thus targeted for degradation via the proteasome (Quesada et al., 2004).CLONING
By searching databases for sequences similar to USP family members, followed by PCR of human cDNA libraries, Quesada et al. (2004) cloned USP47. The deduced protein has a catalytic domain containing a cys box, a QQD box, and a his box, all of which are characteristic of USP enzymes. Northern blot analysis detected high expression of a 5.5-kb transcript in skeletal muscle, with lower expression in testis and heart, and little to no expression in other tissues examined. SKP1 (601434)/CUL1 (603134)/F-box protein (see 609102) (SCF) complexes function as E3 ubiquitin ligases. By mass spectrometric analysis of peptides that immunoprecipitated with an SCF complex containing beta-TRCP2 (FBXW11; 603482) as its F-box protein subunit, Peschiaroli et al. (2010) identified USP47. The deduced full-length protein contains 1,287 amino acids.GENE FUNCTION
Peschiaroli et al. (2010) found that the F-box proteins beta-TRCP1 (BTRC; 603482) and beta-TRCP2, but not other F-box proteins, bound USP47. Mutation analysis revealed that an N-terminal domain of USP47 interacted with the WD40 repeat domain of beta-TRCP. Knockdown of either USP47 or beta-TRCP in several human cell lines reduced cell survival and sensitized cells to pharmacologic induction of apoptosis. However, beta-TRCP did not appear to use USP47 as a substrate or induce its degradation. Conversely, knockdown of USP47 had no effect on beta-TRCP activity.MAPPING
Hartz (2012) mapped the USP47 gene to chromosome 11p15.3 based on an alignment of the USP47 sequence (GenBank GENBANK AK000734) with the genomic sequence (GRCh37).ANIMAL MODEL
Peschiaroli et al. (2010) found that mice homozygous for a hypomorphic Usp47 allele were viable and fertile. However, fibroblasts derived from homozygous mutant embryos were more sensitive than wildtype to ultraviolet radiation-induced apoptosis. ... More on the omim web site
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 614460 was added.