RASGRP1

RAS guanyl releasing protein 1 (calcium and DAG-regulated)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4L9M​, 4L9U​
Identifiers
Symbols	RASGRP1 ; CALDAG-GEFI; CALDAG-GEFII; RASGRP; V; hRasGRP1
External IDs	OMIM: 603962 MGI: 1314635 HomoloGene: 4195 ChEMBL: 5953 GeneCards: RASGRP1 Gene
Gene ontology Molecular function • phosphatidylserine binding • guanyl-nucleotide exchange factor activity • Ras guanyl-nucleotide exchange factor activity • calcium ion binding • zinc ion binding • lipid binding • diacylglycerol binding • phosphatidylcholine binding • protein homodimerization activity Cellular component • Golgi membrane • endoplasmic reticulum membrane • Golgi apparatus • cytosol • plasma membrane • membrane • mast cell granule Biological process • cytokine production • positive regulation of protein phosphorylation • inflammatory response to antigenic stimulus • signal transduction • Ras protein signal transduction • blood coagulation • regulation of phosphatidylinositol 3-kinase signaling • cell differentiation • platelet activation • secretory granule localization • positive regulation of granulocyte macrophage colony-stimulating factor production • positive regulation of tumor necrosis factor production • positive regulation of natural killer cell differentiation • positive regulation of T cell differentiation in thymus • Fc-epsilon receptor signaling pathway • mast cell degranulation • positive regulation of MAP kinase activity • positive regulation of GTPase activity • innate immune response • positive regulation of natural killer cell mediated cytotoxicity • positive regulation of JNK cascade • positive regulation of Ras protein signal transduction • vesicle transport along microtubule • protein oligomerization • regulation of ERK1 and ERK2 cascade • positive regulation of ERK1 and ERK2 cascade • activation of GTPase activity • regulation of phospholipase C activity • regulation of p38MAPK cascade • positive regulation of interferon-gamma secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10125	19419
Ensembl	ENSG00000172575	ENSMUSG00000027347
UniProt	O95267	Q9Z1S3
RefSeq (mRNA)	NM_001128602	NM_011246
RefSeq (protein)	NP_001122074	NP_035376
Location (UCSC)	Chr 15: 38.49 – 38.57 Mb	Chr 2: 117.28 – 117.34 Mb
PubMed search

RAS guanyl-releasing protein 1 is a protein that in humans is encoded by the RASGRP1 gene.^[1][2][3]

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.^[3]

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.^[3]

Clinical significance

Altered expression of the different isoforms of this protein may be a cause of susceptibility to systemic lupus erythematosus (SLE).^[3]

References

1. 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. doi:10.1007/s003359901001. PMID 10087292.
2. 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. doi:10.1073/pnas.95.22.13278. PMC 23782. PMID 9789079.
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. doi:10.1038/79766. PMID 11017103.
• 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. doi:10.1016/S1074-7613(02)00451-X. PMID 12433368.
• 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. doi:10.4049/jimmunol.179.4.2143. PMID 17675473.
• 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. doi:10.4049/jimmunol.177.3.1470. PMID 16849453.
• 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. doi:10.4049/jimmunol.0803521. PMID 20007535.

• Ebinu JO, Bottorff DA, Chan EY, et al. (1998). "RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs.". Science 280 (5366): 1082–6. doi:10.1126/science.280.5366.1082. PMID 9582122.
• Topham MK, Prescott SM (2001). "Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism.". J. Cell Biol. 152 (6): 1135–43. doi:10.1083/jcb.152.6.1135. PMC 2199204. PMID 11257115.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Bivona TG, Pérez De Castro I, Ahearn IM, et al. (2003). "Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1.". Nature 424 (6949): 694–8. doi:10.1038/nature01806. PMID 12845332.
• Madani S, Hichami A, Cherkaoui-Malki M, et al. (2004). "Diacylglycerols containing Omega 3 and Omega 6 fatty acids bind to RasGRP and modulate MAP kinase activation.". J. Biol. Chem. 279 (2): 1176–83. doi:10.1074/jbc.M306252200. PMID 14583629.
• Klinger MB, Guilbault B, Goulding RE, Kay RJ (2005). "Deregulated expression of RasGRP1 initiates thymic lymphomagenesis independently of T-cell receptors.". Oncogene 24 (16): 2695–704. doi:10.1038/sj.onc.1208334. PMID 15829980.
• Liu Y, Zhu M, Nishida K, et al. (2007). "An essential role for RasGRP1 in mast cell function and IgE-mediated allergic response.". J. Exp. Med. 204 (1): 93–103. doi:10.1084/jem.20061598. PMC 2118421. PMID 17190838.
• Roose JP, Mollenauer M, Ho M, et al. (2007). "Unusual interplay of two types of Ras activators, RasGRP and SOS, establishes sensitive and robust Ras activation in lymphocytes.". Mol. Cell. Biol. 27 (7): 2732–45. doi:10.1128/MCB.01882-06. PMC 1899892. PMID 17283063.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry.". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Pasvolsky R, Feigelson SW, Kilic SS, et al. (2007). "A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets.". J. Exp. Med. 204 (7): 1571–82. doi:10.1084/jem.20070058. PMC 2118641. PMID 17576779.
• Kosco KA, Cerignoli F, Williams S, et al. (2007). "SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1.". Mol. Immunol. 45 (2): 510–22. doi:10.1016/j.molimm.2007.05.024. PMID 17658605.
• Yasuda S, Stevens RL, Terada T, et al. (2007). "Defective expression of Ras guanyl nucleotide-releasing protein 1 in a subset of patients with systemic lupus erythematosus.". J. Immunol. 179 (7): 4890–900. doi:10.4049/jimmunol.179.7.4890. PMID 17878389.

External links

• RASGRP1 human gene location in the UCSC Genome Browser.
• RASGRP1 human gene details in the UCSC Genome Browser.

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