Ubiquitin carboxyl-terminal hydrolase 5 (USP5)
The protein contains 858 amino acids for an estimated molecular weight of 95786 Da.
Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition. (updated: April 1, 2015)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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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The reference OMIM entry for this protein is 601447
Ubiquitin-specific protease 5; usp5
Isopeptidase t; isot
DESCRIPTION
Ubiquitin (see 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995).CLONING
Wilkinson et al. (1995) purified a 93-kD bovine protein with the properties expected of a polyubiquitin disassembly protein. They biochemically characterized the enzyme, which they called isopeptidase T (ISOT), and cloned a cDNA encoding the human homolog (GenBank U35116). The deduced 835-amino acid human polypeptide has a predicted molecular mass of 93.3 kD. Ansari-Lari et al. (1996) generated the genomic sequence of the human CD4 gene (186940) and its neighboring region on chromosome 12 using the large-scale shotgun sequencing strategy. A total of 117 kb of genomic sequence and approximately 11 kb of cDNA sequence was obtained. They identified in this sequence 8 genes, including CD4 and ISOT. Using a battery of strategies, the exon/intron boundaries, splice variants, and tissue expression patterns of the genes were determined. Tissue expression analysis indicated a high level of expression of a 3.3-kb ISOT transcript in brain, and a low level of expression in heart, lung, spleen, and skeletal muscle. Sequence comparison showed that ISOT is a member of the ubiquitin C-terminal hydroxylase family. Wilkinson et al. (1995) originally cloned human ISOT and reported the sequence as 3,102 bp long. Ansari-Lari et al. (1996) stated that comparison of their cDNA sequence with the sequence reported by Wilkinson et al. (1995) indicated alternative splicing in exon 15. Four nucleotide differences were found between the 2 sequences resulting in lys-to-arg and gly-to-asp substitutions. The cDNA and genomic sequences were in full agreement. Reyes-Turcu et al. (2006) stated that the 835-amino acid human USP5 protein contains 4 putative ubiquitin-binding domains: an N-terminal zinc finger ubiquitin-binding domain (ZNF-UBP), a ubiquitin-specific processing protease (UBP) domain formed by noncontiguous regions containing the active-site cys and his boxes, and 2 ubiquitin-associated domains (UBA1 and UBA2). UBA1 and UBA2 are located between the cys and his boxes, which are in the central and C-terminal regions of USP5, respectively.BIOCHEMICAL FEATURES
Reyes-Turcu et al. (2006) reported the crystal structures of the ZNF-UBP domain of USP5 alone and in complex with ubiquitin at 2.09-angstrom resolution. They found that, unlike other ubiquitin-binding domains, the ZNF-UBP domain contains a deep binding pocket where the C-terminal diglycine motif of ubiquitin is inserted, thus explaining the specificity of USP5 for an unmodified C terminus on the proximal subunit of polyubiquitin. Mutation analysis showed that the ZNF-UBP domain was required for optimal catalytic activation of USP5.MAPPING
By genomic sequence analysis, Ansari-Lari et al. (1996) mapped the USP5 gene to chromosome 12p13, near the CD4 gene (186940). ... More on the omim web site
May 13, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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 601447 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed