RASGRP1

RASGRP1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesRASGRP1, CALDAG-GEFI, CALDAG-GEFII, RASGRP, V, hRasGRP1, RAS guanyl releasing protein 1
External IDsMGI: 1314635 HomoloGene: 4195 GeneCards: RASGRP1
Gene location (Human)
Chr.Chromosome 15 (human)[1]
BandNo data availableStart38,488,103 bp[1]
End38,565,575 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

10125

19419

Ensembl

ENSG00000172575

ENSMUSG00000027347

UniProt

O95267

Q9Z1S3

RefSeq (mRNA)

NM_001128602
NM_001306086
NM_005739

NM_011246

RefSeq (protein)

NP_001122074
NP_001293015
NP_005730

NP_035376

Location (UCSC)Chr 15: 38.49 – 38.57 MbChr 15: 117.28 – 117.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

RAS guanyl-releasing protein 1 is a protein that in humans is encoded by the RASGRP1 gene.[5][6][7]

Function

RAS guanyl nucleotide-releasing protein (RASGRP) is a member of a family of genes characterized by the presence of a Ras superfamily guanine nucleotide exchange factor (GEF) domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. It activates the Erk/MAP kinase cascade and regulates T-cells and B-cells development, homeostasis and differentiation.[7]

Gene

Alternatively spliced transcript variants encoding different isoforms have been identified. The corresponding rat gene rbc7, which lacks a 5-prime exon, represents a 5-prime and 3-prime truncated version of a larger normal rat transcript that encodes a predicted 90-kD protein. This shorter transcript has not been found in humans.[7]

Clinical significance

In November 2016 a 12-year-old patient was hospitalized for repetitive infections. Scientists have assumed that a genetic problem might be the reason. More specifically, the genetic cause is a defect of the RASGRP1 gene which makes it inactive. .

RASGRP1 plays a role in the functions of natural killer cell dyneins. Since dyneins are motor proteins, their function is to circulate the elements inside the cells. Dr. Orange's laboratory studies have established a functional link between the defects of natural killer cells and dyneins, which in combination with Other observations led doctors to try the drug lenalidommide to treat the patient. The drug was able to reverse certain effects of the mutation RASGRP1.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000172575 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000027347 - Ensembl, May 2017
  3. "Human PubMed Reference:".
  4. "Mouse PubMed Reference:".
  5. Bottorff D, Ebinu J, Stone JC (May 1999). "RasGRP, a Ras activator: mouse and human cDNA sequences and chromosomal positions". Mamm Genome. 10 (4): 358–61. PMID 10087292. doi:10.1007/s003359901001.
  6. Kawasaki H, Springett GM, Toki S, Canales JJ, Harlan P, Blumenstiel JP, Chen EJ, Bany IA, Mochizuki N, Ashbacher A, Matsuda M, Housman DE, Graybiel AM (Nov 1998). "A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia". Proc Natl Acad Sci U S A. 95 (22): 13278–83. PMC 23782Freely accessible. PMID 9789079. doi:10.1073/pnas.95.22.13278.
  7. 1 2 3 "Entrez Gene: RASGRP1 RAS guanyl releasing protein 1 (calcium and DAG-regulated)".

Further reading

  • Dower NA, Stang SL, Bottorff DA, Ebinu JO, Dickie P, Ostergaard HJ, Stone JC (2000). "RasGRP is essential for mouse thymocyte differentiation and TCR signaling.". Nature Immunology. 1 (4): 317–21. PMID 11017103. doi:10.1038/79766. 
  • Priatel JJ, Teh SJ, Dower NA, Stone JC, et al. (2002). "RasGRP1 Transduces Low-Grade TCR Signals Which Are Critical For T Cell Development, Homeostasis and Differentiation.". Immunity. 17 (5): 617–27. PMID 12433368. doi:10.1016/S1074-7613(02)00451-X. 
  • Priatel JJ, Chen X, Zenewicz LA, Shen H, Harder KW, Horwitz MS, et al. (2007). "Chronic Immunodeficiency in Mice Lacking RasGRP1 Results in CD4 T Cell Immune Activation and Exhaustion.". J. Immunol. 179 (4): 2143–52. PMID 17675473. doi:10.4049/jimmunol.179.4.2143. 
  • Priatel JJ, Chen X, Dhanji S, Abraham N, et al. (2006). "RasGRP1 Transmits Pro-Differentiation TCR Signaling that is Crucial for CD4 T Cell Development.". J. Immunol. 177 (3): 1470–80. PMID 16849453. doi:10.4049/jimmunol.177.3.1470. 
  • Priatel JJ, Chen X, Huang YH, Chow MT, Zenewicz LA, Coughlin JJ, Shen H, Stone JC, Tan R, et al. (2010). "RasGRP1 regulates antigen-induced developmental programming by naive CD8 T cells.". J. Immunol. 184 (2): 666–76. PMID 20007535. doi:10.4049/jimmunol.0803521. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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