RASGRP1

RASGRP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4L9M, 4L9U
Identifiers
Aliases	RASGRP1 , CALDAG-GEFI, CALDAG-GEFII, RASGRP, hRasGRP1, RAS guanyl releasing protein 1, IMD64
External IDs	OMIM: 603962 MGI: 1314635 HomoloGene: 4195 GeneCards: RASGRP1
Gene location (Human) Chr. Chromosome 15 (human) [1] Band 15q14 Start 38,488,103 bp [1] End 38,565,575 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 E5|2 59.19 cM Start 117,110,474 bp [2] End 117,173,482 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in pons cerebellar vermis Brodmann area 23 endothelial cell Brodmann area 46 entorhinal cortex cerebellar hemisphere orbitofrontal cortex middle temporal gyrus thymus Top expressed in olfactory tubercle lateral geniculate nucleus medial geniculate nucleus medial dorsal nucleus subiculum nucleus accumbens pontine nuclei superior frontal gyrus globus pallidus primary motor cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium 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 activity Cellular component cytoplasm Golgi apparatus endoplasmic reticulum membrane membrane mast cell granule Golgi membrane endoplasmic reticulum cytosol plasma membrane intracellular anatomical structure Biological process cell 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 transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 2: 117.11 – 117.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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. GRCh38: Ensembl release 89: ENSG00000172575 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027347 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. doi:10.1007/s003359901001. PMID   10087292. S2CID   34266456.
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. Bibcode:1998PNAS...9513278K. doi: 10.1073/pnas.95.22.13278 . PMC   23782 . PMID   9789079.
7. "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. 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, 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.
• 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.