Ubiquitin carboxyl-terminal hydrolase 4 (USP4)
The protein contains 963 amino acids for an estimated molecular weight of 108565 Da.
Deubiquitinating enzyme that removes conjugated ubiquitin from target proteins (PubMed:16316627, PubMed:16472766, PubMed:16339847, PubMed:20595234, PubMed:22347420, PubMed:25404403). Deubiquitinates PDPK1 (PubMed:22347420). Deubiquitinates TRIM21 (PubMed:16316627). Deubiquitinates receptor ADORA2A which increases the amount of functional receptor at the cell surface (PubMed:16339847). May regulate mRNA splicing through deubiquitination of the U4 spliceosomal protein PRPF3 (PubMed:20595234). This may prevent its recognition by the U5 component PRPF8 thereby destabilizing interactions within the U4/U6.U5 snRNP (PubMed:20595234). May also play a role in the regulation of quality control in the ER (PubMed:16339847). (updated: Dec. 5, 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.
- 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.
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.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs9311440 |
Biological Process
Negative regulation of protein ubiquitination
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein deubiquitination
Protein localization to cell surface
Regulation of proteasomal protein catabolic process
Regulation of protein stability
Spliceosomal tri-snRNP complex assembly
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 603486
Ubiquitin-specific protease 4; usp4
Ubiquitin-specific protease; unp
DESCRIPTION
The ubiquitin-specific proteases (UBPs) are a group of deubiquitinating enzymes that possess 2 signature motifs, the Cys box and the His box (summary by Frederick et al., 1998).CLONING
Gupta et al. (1993) isolated mouse cDNAs encoding Unp, a protein similar to the human TRE oncogene. Using Western blots, Gupta et al. (1994) found that Unp has an apparent molecular mass of 180 kD. They reported that overexpression of Unp led to oncogenic transformation of NIH 3T3 cells injected into athymic mice. By screening a human frontal cortex library with a murine Unp cDNA, Gray et al. (1995) isolated cDNAs encoding human UNP. Analysis of the clones revealed a large open reading with the potential to encode a protein of 854 amino acids, with a molecular mass of 97 kD. The human and mouse proteins share 90% sequence identity. Northern blot analysis of primary lung tumor samples indicated that levels of UNP mRNA were elevated in small cell carcinomas and adenocarcinomas relative to normal adult lung. Frederick et al. (1998) sequenced additional UNP cDNAs and found several differences from the sequence reported by Gray et al. (1995), including 2 single nucleotide insertions that increased the length of the predicted protein, UNPEL (UNP extended, long isoform), to 963 amino acids. They also recovered cDNAs encoding a shorter isoform designated UNPES. Both isoforms exhibited deubiquitinating activity. Antibodies against UNP detected 2 proteins of 105 to 110 kD on Western blots. Using immunocytochemistry of mammalian cells expressing epitope-tagged UNP and cell fractionation studies, Frederick et al. (1998) demonstrated that both isoforms of the human protein are localized primarily in the cytosol. (In an erratum, Frederick et al. (1998) cited a personal communication from the Gray laboratory stating that the data in Gupta et al. (1993) locating Unp in the nuclear fraction of mammalian cell extracts was apparently in error.) Northern blot analysis revealed UNP expression as a closely-migrating cluster of mRNAs in all tissues tested. However, the authors found no evidence for overexpression of UNP transcripts in cell lines derived from small cell lung carcinomas.GENE STRUCTURE
Di Fruscio et al. (1998) reported that the mouse Unp gene contains 22 exons distributed over 47 kb. A processed ribosomal S2 pseudogene was identified in the third intron.MAPPING
By analysis of an interspecific backcross, Gupta et al. (1993) mapped the Unp gene to mouse chromosome 9 in a region showing homology of synteny with human chromosome 3p. By fluorescence in situ hybridization, Gray et al. (1995) mapped the human UNP gene to 3p21.3, a region implicated in neoplasms of the lung. Using the same technique, Frederick et al. (1998) refined the map position to 3p21.31. ... More on the omim web site
Dec. 9, 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 603486 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed