Serine/threonine-protein kinase OSR1 (OXSR1)
The protein contains 527 amino acids for an estimated molecular weight of 58022 Da.
Phosphorylates RELL1, RELL2 and RELT (PubMed:16389068, PubMed:28688764). Phosphorylates PAK1 (PubMed:14707132). Phosphorylates PLSCR1 in the presence of RELT (PubMed:22052202). (updated: Nov. 7, 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs6599079 | |
| dbSNP:rs35295772 | |
| a metastatic melanoma sample; somatic mutation |
Biological Process
Activation of protein kinase activity
Cellular hypotonic response
Cellular response to chemokine
Chemokine (C-C motif) ligand 21 signaling pathway
Chemokine (C-X-C motif) ligand 12 signaling pathway
Intracellular signal transduction
Negative regulation of potassium ion transmembrane transporter activity
Obsolete negative regulation of rubidium ion transmembrane transporter activity
Osmosensory signaling pathway
Peptidyl-threonine phosphorylation
Positive regulation of T cell chemotaxis
Protein autophosphorylation
Protein phosphorylation
Regulation of apoptotic process
Regulation of mitotic cell cycle
Response to oxidative stress
Signal transduction
Signal transduction by protein phosphorylation
Signal transduction by trans-phosphorylation
Stress-activated protein kinase signaling cascade
The reference OMIM entry for this protein is 604046
Oxidative stress-responsive 1; oxsr1
Osr1
CLONING
The 3p22-p21.3 chromosomal region is one of 3 regions of 3p that is commonly deleted in various carcinomas. By analyzing a cloned segment from this region, Tamari et al. (1999) identified OXSR1, which they designated OSR1, because the predicted 527-amino acid protein shares 39% identity with Ste20/oxidant stress-response kinase-1 (STK25; 602255). Northern blot analysis detected a 4.6-kb major transcript in all tissues tested. A less abundant 7.5-kb mRNA was detected in heart and skeletal muscle. Using RT-PCR, Chen et al. (2004) isolated an OXSR1 cDNA from HeLa cell RNA. The deduced 527-amino acid protein has a calculated molecular mass of 58 kD. OXSR1 contains an N-terminal Ste20-like serine/threonine kinase domain and 2 C-terminal regions, designated PF1 and PF2, conserved with other members of the germinal center kinase (GCK) VI subfamily of Ste20 kinases, such as SPAK (STK39; 607648). At the end of the PF1 domain, OXSR1 has a putative caspase-3 (CASP3; 600636) cleavage site. Western blot analysis detected Oxsr1 at an apparent molecular mass of 58 kD in all mouse tissues examined except thymus. Cell fractionation and immunofluorescence analysis of HeLa cells showed that OXSR1 was distributed throughout the cell.GENE FUNCTION
Chen et al. (2004) found that OXSR1 could phosphorylate a test substrate and itself. Of the potential regulators surveyed, endogenous OXSR1 was activated only by osmotic stresses, notably sorbitol and, to a lesser extent, NaCl. A 2-hybrid screen identified PAK1 (602590) as an OXSR1 target protein. OXSR1 phosphorylated thr84 within the N-terminal regulatory domain of PAK1. Replacement of thr84 with gln reduced activation of PAK1 by an active form of the small G protein CDC42 (116952), suggesting that phosphorylation by OXSR1 modulates the G protein sensitivity of PAK. By yeast 2-hybrid analysis of Jurkat human T cells and immunoprecipitation analysis of human embryonic kidney cells and HeLa cells, Anselmo et al. (2006) showed that OXSR1 and WNK1 (605232) interacted through conserved C-terminal motifs. OSR1 was phosphorylated in a WNK1-dependent manner, and depletion of WNK1 from HeLa cells with small interfering RNA reduced OXSR1 kinase activity. Depletion of either WNK1 or OXSR1 reduced Na-K-Cl cotransporter (NKCC; see 600839) activity, suggesting that WNK1 and OSR1 are required for NKCC function.GENE STRUCTURE
Tamari et al. (1999) determined that the OXSR1 gene contains 18 exons and spans approximately 90 kb.MAPPING
Daigo et al. (1999) reported that the OXSR1 gene is located between the OCTL1 (604047) and MYD88 (602170) genes on chromosome 3p22-p21.3. ... More on the omim web site
Nov. 16, 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604046 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed