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]
Geneedit
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 significanceedit
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.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000172575 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000027347 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^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. S2CID 34266456.
^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. Bibcode:1998PNAS...9513278K. doi:10.1073/pnas.95.22.13278. PMC23782. PMID 9789079.
^ abc"Entrez Gene: RASGRP1 RAS guanyl releasing protein 1 (calcium and DAG-regulated)".
Further readingedit
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. S2CID 7724240.
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. Bibcode:1998Sci...280.1082E. 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. PMC2199204. 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. 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. Bibcode:2003Natur.424..694B. doi:10.1038/nature01806. PMID 12845332. S2CID 4403046.
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. S2CID 23262099.
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. PMC2118421. 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. PMC1899892. 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. PMC1847948. 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. PMC2118641. 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.
rasgrp1, guanyl, releasing, protein, protein, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes4l9m, 4l9uidentifiersaliases, caldag, gefi, caldag, gefii, rasgrp, hrasgrp1, guanyl, releasing, protein, imd64external, id. RAS guanyl releasing protein 1 is a protein that in humans is encoded by the RASGRP1 gene 5 6 7 RASGRP1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes4L9M 4L9UIdentifiersAliasesRASGRP1 CALDAG GEFI CALDAG GEFII RASGRP hRasGRP1 RAS guanyl releasing protein 1 IMD64External IDsOMIM 603962 MGI 1314635 HomoloGene 4195 GeneCards RASGRP1Gene location Human Chr Chromosome 15 human 1 Band15q14Start38 488 103 bp 1 End38 565 575 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 E5 2 59 19 cMStart117 110 474 bp 2 End117 173 482 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inponscerebellar vermisBrodmann area 23endothelial cellBrodmann area 46entorhinal cortexcerebellar hemisphereorbitofrontal cortexmiddle temporal gyrusthymusTop expressed inolfactory tuberclelateral geniculate nucleusmedial geniculate nucleusmedial dorsal nucleussubiculumnucleus accumbenspontine nucleisuperior frontal gyrusglobus pallidusprimary motor cortexMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functioncalcium ion binding protein homodimerization activity phosphatidylcholine binding zinc ion binding phosphatidylserine binding metal ion binding diacylglycerol binding lipid binding guanyl nucleotide exchange factor activity GTPase activator activityCellular componentcytoplasm Golgi apparatus endoplasmic reticulum membrane membrane mast cell granule Golgi membrane endoplasmic reticulum cytosol plasma membrane intracellular anatomical structureBiological processcell differentiation positive regulation of protein phosphorylation positive regulation of T cell differentiation in thymus intracellular signal transduction regulation of phospholipase C activity positive regulation of MAP kinase activity positive regulation of natural killer cell differentiation inflammatory response to antigenic stimulus vesicle transport along microtubule activation of GTPase activity regulation of GTPase activity cytokine production positive regulation of Ras protein signal transduction positive regulation of natural killer cell activation positive regulation of JNK cascade secretory granule localization MAPK cascade regulation of phosphatidylinositol 3 kinase signaling positive regulation of GTPase activity positive regulation of granulocyte macrophage colony stimulating factor production protein complex oligomerization positive regulation of ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of tumor necrosis factor production Ras protein signal transduction mast cell degranulation regulation of p38MAPK cascade positive regulation of natural killer cell mediated cytotoxicity signal transduction small GTPase mediated signal transductionSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez1012519419EnsemblENSG00000172575ENSMUSG00000027347UniProtO95267Q9Z1S3RefSeq mRNA NM 001128602NM 001306086NM 005739NM 011246RefSeq protein NP 001122074NP 001293015NP 005730NP 035376Location UCSC Chr 15 38 49 38 57 MbChr 2 117 11 117 17 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Gene 3 Clinical significance 4 References 5 Further reading 6 External linksFunction editRAS 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 editAlternatively 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 editIn 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 edit a b c GRCh38 Ensembl release 89 ENSG00000172575 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000027347 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine 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 S2CID 34266456 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 Bibcode 1998PNAS 9513278K doi 10 1073 pnas 95 22 13278 PMC 23782 PMID 9789079 a b c Entrez Gene RASGRP1 RAS guanyl releasing protein 1 calcium and DAG regulated Further reading editDower 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 S2CID 7724240 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 Bibcode 1998Sci 280 1082E 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 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Bivona TG Perez 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 Bibcode 2003Natur 424 694B doi 10 1038 nature01806 PMID 12845332 S2CID 4403046 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 S2CID 23262099 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 editRASGRP1 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 nbsp This article on a gene on human chromosome 15 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title RASGRP1 amp oldid 1193714378, 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