Regulator of G-protein signaling 10 (RGS10)
The protein contains 173 amino acids for an estimated molecular weight of 20236 Da.
Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the muscarinic acetylcholine receptor CHRM2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:8774883, PubMed:10608901, PubMed:9353196, PubMed:11443111, PubMed:18434541). Modulates the activity of potassium channels that are activated in response to CHRM2 signaling (PubMed:11443111). Activity on GNAZ is inhibited by palmitoylation of the G-protein (PubMed:9353196). (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 annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs1802228 |
Biological Process
G protein-coupled acetylcholine receptor signaling pathway
G protein-coupled receptor signaling pathway
Negative regulation of signal transduction
Positive regulation of GTPase activity
Regulation of G protein-coupled receptor signaling pathway
Response to amphetamine
Termination of G-protein coupled receptor signaling pathway
Cellular Component
Axon terminus
Cytoplasm
Cytosol
Dendritic spine
Neuronal cell body
Nucleus
Plasma membrane
The reference OMIM entry for this protein is 602856
Regulator of g protein signaling 10; rgs10
DESCRIPTION
RGS proteins negatively regulate signaling pathways involving 7-transmembrane receptors and heterotrimeric G proteins. See 602189 for background.CLONING
Using a yeast 2-hybrid system with a mutationally activated form of rat G-alpha(i3) as the bait, Hunt et al. (1996) isolated HeLa cell cDNAs encoding RGS10. Like all members of the RGS family, the predicted 173-amino acid RGS10 contains a 120-amino acid core domain that is strongly conserved with the yeast Sst2 protein. Northern blot analysis detected an approximately 900-bp RGS10 transcript in HeLa cells, human embryonic kidney 293 cells, and mouse brain. By microarray analysis, Yang and Li (2007) found that RGS10 was highly expressed in human osteoclastoma. Northern blot analysis confirmed high RGS10 expression in osteoclastoma and detected weaker expression in brain, liver, kidney, and the Hep2 cell line; no expression was detected in other tissues and cell lines examined. Mouse Rgs10 was highly expressed in preosteoclasts and osteoclasts derived from RANKL (TNFSF11; 602642)-stimulated bone marrow-derived monocytes, but it was not expressed in osteoblasts or preosteoblasts.GENE FUNCTION
Using coimmunoprecipitation studies, Hunt et al. (1996) demonstrated that RGS10 associates specifically with the activated forms of the 2 related G protein subunits G-alpha(i3) and G-alpha(z) but fails to interact with the structurally and functionally distinct G-alpha(s) subunit. In vitro assays indicated that RGS10 potently and selectively increases the GTP hydrolytic activity of several G-alpha(i) family members. Using human T cells silenced for or overexpressing RGS10, Garcia-Bernal et al. (2011) showed that RGS10 inhibited G-alpha-dependent, chemokine-upregulated T-cell adhesion mediated by alpha-4 (ITGA4; 192975)/beta-1 (ITGB1; 135630) and alpha-L (ITGAL; 153370)/beta-2 (ITGB2; 600065) integrins. The data suggested that RGS10 opposes activation by chemokines of the VAV1 (164875)-RAC1 (602048) pathway in T cells, leading to repression of adhesion strengthening mediated by alpha-4/beta-1. RGS10 also limited adhesion-independent cell chemotaxis and activation of CDC42 (116952).GENE STRUCTURE
Sierra et al. (2002) determined that the RGS10 gene contains 5 exons and spans 35 kb.MAPPING
By genomic sequence analysis, Sierra et al. (2002) mapped the RGS10 gene to chromosome 10q26.11. They mapped the mouse Rgs10 gene to chromosome 7 by interspecific backcross mapping.ANIMAL MODEL
Yang and Li (2007) obtained Rgs10 -/- mice at the expected mendelian ratio, but they were smaller and had shorter limbs than their wildtype littermates. Growth retardation became apparent during the first or second postnatal week. Histologically, Rgs10 -/- mice exhibited severe osteopetrosis. Disruption of Rgs10 impaired osteoclast differentiation due to the absence of calcium current oscillations and loss of Nfatc1 (600489) expression. Ectopic expression of Rgs10 markedly enhanced Rankl-induced osteoclast differentiation. Rgs10 competitively bound Ca(2+)/calmodulin (see CALM1; 114180) and phosphatidylinositol 3-phosphate in a Ca(2+)-dependent manner. Yang and Li (2007) concluded that RGS10 is a key regulator of Ca(2+) current oscillations during osteoclast differentiation. ... 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602856 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed