RASGRP2 explained

RAS guanyl-releasing protein 2 is a protein that in humans is encoded by the RASGRP2 gene.^{[1] [2]}

The protein encoded by this gene is a brain-enriched nucleotide exchange factor that contains an N-terminal GEF domain, 2 tandem repeats of EF-hand calcium-binding motifs, and a C-terminal diacylglycerol/phorbol ester-binding domain. This protein can activate small GTPases, including RAS and RAP1/RAS3. The nucleotide exchange activity of this protein can be stimulated by calcium and diacylglycerol. Two alternatively spliced transcript variants of this gene, encoding distinct isoforms, have been reported.

Clinical significance

Mutations in RASGRP2 are associated with severe bleeding.^[3]

Further reading

• Kedra D, Seroussi E, Fransson I, etal . The germinal center kinase gene and a novel CDC25-like gene are located in the vicinity of the PYGM gene on 11q13. . Hum. Genet. . 100 . 5–6 . 611–9 . 1997 . 9341881 . 10.1007/s004390050562 . 10402419 .
• Clyde-Smith J, Silins G, Gartside M, etal . Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. . J. Biol. Chem. . 275 . 41 . 32260–7 . 2000 . 10918068 . 10.1074/jbc.M006087200 . 21096691 . free .
• Guo FF, Kumahara E, Saffen D . A CalDAG-GEFI/Rap1/B-Raf cassette couples M(1) muscarinic acetylcholine receptors to the activation of ERK1/2. . J. Biol. Chem. . 276 . 27 . 25568–81 . 2001 . 11292831 . 10.1074/jbc.M101277200 . free .
• Toki S, Kawasaki H, Tashiro N, etal . Guanine nucleotide exchange factors CalDAG-GEFI and CalDAG-GEFII are colocalized in striatal projection neurons. . J. Comp. Neurol. . 437 . 4 . 398–407 . 2001 . 11503142 . 10.1002/cne.1291 . 35740815 .
• Eto K, Murphy R, Kerrigan SW, etal . Megakaryocytes derived from embryonic stem cells implicate CalDAG-GEFI in integrin signaling. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 20 . 12819–24 . 2002 . 12239348 . 10.1073/pnas.202380099 . 130543 . 2002PNAS...9912819E . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Katagiri K, Shimonaka M, Kinashi T . Rap1-mediated lymphocyte function-associated antigen-1 activation by the T cell antigen receptor is dependent on phospholipase C-gamma1. . J. Biol. Chem. . 279 . 12 . 11875–81 . 2004 . 14702343 . 10.1074/jbc.M310717200 . free .
• Kimura K, Wakamatsu A, Suzuki Y, etal . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 .

Notes and References

1. 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 . A Rap guanine nucleotide exchange factor enriched highly in the basal ganglia . Proc Natl Acad Sci U S A . 95 . 22 . 13278–83 . Nov 1998 . 9789079 . 23782 . 10.1073/pnas.95.22.13278 . 1998PNAS...9513278K . free .
2. Web site: Entrez Gene: RASGRP2 RAS guanyl releasing protein 2 (calcium and DAG-regulated).
3. 24958846. 2014. Canault. M. Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding. Journal of Experimental Medicine. Ghalloussi. D. Grosdidier. C. Guinier. M. Perret. C. Chelghoum. N. Germain. M. Raslova. H. Peiretti. F. Morange. P. E.. Saut. N. Pillois. X. Nurden. A. T.. Cambien. F. Pierres. A. Van Den Berg. T. K.. Kuijpers. T. W.. Alessi. M. C.. Tregouet. D. A.. 10.1084/jem.20130477 . 211 . 7. 1349–62 . 4076591.