Ubiquitin carboxyl-terminal hydrolase 19 (USP19)
The protein contains 1318 amino acids for an estimated molecular weight of 145651 Da.
Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked ubiquitin chains. (updated: Oct. 25, 2017)
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.
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 predicted to be membranous by TOPCONS.
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| Variant | Description |
|---|---|
| dbSNP:rs11552724 |
Biological Process
Negative regulation of proteasomal protein catabolic process
Negative regulation of skeletal muscle tissue development
Positive regulation of cell cycle process
Protein deubiquitination
Protein stabilization
Regulation of cellular response to hypoxia
Regulation of ERAD pathway
Regulation of proteasomal protein catabolic process
Regulation of protein stability
Response to endoplasmic reticulum stress
Ubiquitin-dependent ERAD pathway
The reference OMIM entry for this protein is 614471
Ubiquitin-specific protease 19; usp19
Kiaa0891
DESCRIPTION
USP19 is a ubiquitin protein ligase (EC 3.4.19.12) with a role in regulating cell cycle progression (Lu et al., 2009).CLONING
By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (1998) cloned USP19, which they designated KIAA0891. The deduced 1,371-amino acid protein shares significant similarity with the ubiquitin protease UNPH (USP4; 603486). RT-PCR ELISA detected highest expression in fetal liver, followed by adult spinal cord. All other tissues, including adult and fetal brain, showed much lower expression, and no expression was detected in spleen.GENE FUNCTION
p27(KIP1) (CDKN1B; 600778) is a cyclin-dependent kinase inhibitor that regulates the G1/S transition. Using rat myoblast and fibroblast cell lines, Lu et al. (2009) showed that Usp19 regulated p27(KIP1) levels by deubiquitinating and stabilizing Kpc1 (RNF123; 614472), an E3 ubiquitin ligase that ubiquitinates cytosolic p27(KIP1) and targets it for proteasomal degradation at G1 phase. Immunoprecipitation analysis revealed that Usp19 interacted directly with Kpc1. Knockdown of Usp19 resulted in loss of Kpc1, accumulation of p27(KIP1), inhibition of cell proliferation, and slower progression from G0/G1 to S phase.MAPPING
By radiation hybrid analysis, Nagase et al. (1998) mapped the USP19 gene to chromosome 3. Hartz (2011) mapped the USP19 gene to chromosome 3p21.31 based on an alignment of the USP19 sequence (GenBank GENBANK AB020698) with the genomic sequence (GRCh37). ... 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 614471 was added.