Hmdb loader
Identification
HMDB Protein ID HMDBP12140
Secondary Accession Numbers None
Name RAS guanyl-releasing protein 1
Synonyms
  1. Calcium and DAG-regulated guanine nucleotide exchange factor II
  2. Ras guanyl-releasing protein
  3. CalDAG-GEFII
Gene Name RASGRP1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Functions as a calcium- and diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Regulates T-cell/B-cell development, homeostasis and differentiation by coupling T-lymphocyte/B-lymphocyte antigen receptors to Ras. Regulates NK cell cytotoxicity and ITAM-dependent cytokine production by activation of Ras-mediated ERK and JNK pathways (By similarity). Functions in mast cell degranulation and cytokine secretion, regulating FcERI-evoked allergic responses (PubMed:17190838). May also function in differentiation of other cell types. Proto-oncogene, which promotes T-cell lymphomagenesis when its expression is deregulated (PubMed:15829980, PubMed:17210708).
Pathways
  • MAPK signaling pathway
  • PD-L1 expression and PD-1 checkpoint pathway in cancer
  • Platelet activation
  • Ras signaling pathway
  • T cell receptor signaling pathway
Reactions Not Available
GO Classification
Biological Process
positive regulation of granulocyte macrophage colony-stimulating factor production
positive regulation of MAP kinase activity
T cell proliferation
regulation of ERK1 and ERK2 cascade
B cell proliferation
activation of GTPase activity
B cell activation
inflammatory response to antigenic stimulus
mast cell degranulation
natural killer cell activation
positive regulation of Ras protein signal transduction
positive regulation of GTPase activity
positive regulation of interferon-gamma production
positive regulation of natural killer cell activation
positive regulation of natural killer cell differentiation
positive regulation of natural killer cell mediated cytotoxicity
positive regulation of tumor necrosis factor production
secretory granule localization
vesicle transport along microtubule
small GTPase mediated signal transduction
cell differentiation
positive regulation of T cell differentiation in thymus
T cell activation
positive regulation of ERK1 and ERK2 cascade
positive regulation of JNK cascade
regulation of phosphatidylinositol 3-kinase cascade
positive regulation of protein phosphorylation
Cellular Component
Golgi apparatus
Golgi membrane
endoplasmic reticulum membrane
plasma membrane
cytosol
Molecular Function
diacylglycerol binding
phosphatidylcholine binding
guanyl-nucleotide exchange factor activity
identical protein binding
calcium ion binding
zinc ion binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 795
Molecular Weight 90303.04
Theoretical pI 8.107
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9Z1S3
UniProtKB/Swiss-Prot Entry Name GRP1_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Bottorff D, Ebinu J, Stone JC: RasGRP, a Ras activator: mouse and human cDNA sequences and chromosomal positions. Mamm Genome. 1999 Apr;10(4):358-61. [PubMed:10087292 ]
  4. Bivona TG, Perez De Castro I, Ahearn IM, Grana TM, Chiu VK, Lockyer PJ, Cullen PJ, Pellicer A, Cox AD, Philips MR: Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1. Nature. 2003 Aug 7;424(6949):694-8. Epub 2003 Jun 29. [PubMed:12845332 ]
  5. Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26. [PubMed:19468303 ]
  6. Tognon CE, Kirk HE, Passmore LA, Whitehead IP, Der CJ, Kay RJ: Regulation of RasGRP via a phorbol ester-responsive C1 domain. Mol Cell Biol. 1998 Dec;18(12):6995-7008. doi: 10.1128/MCB.18.12.6995. [PubMed:9819387 ]
  7. Dower NA, Stang SL, Bottorff DA, Ebinu JO, Dickie P, Ostergaard HL, Stone JC: RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nat Immunol. 2000 Oct;1(4):317-21. doi: 10.1038/79766. [PubMed:11017103 ]
  8. Priatel JJ, Teh SJ, Dower NA, Stone JC, Teh HS: RasGRP1 transduces low-grade TCR signals which are critical for T cell development, homeostasis, and differentiation. Immunity. 2002 Nov;17(5):617-27. doi: 10.1016/s1074-7613(02)00451-x. [PubMed:12433368 ]
  9. Layer K, Lin G, Nencioni A, Hu W, Schmucker A, Antov AN, Li X, Takamatsu S, Chevassut T, Dower NA, Stang SL, Beier D, Buhlmann J, Bronson RT, Elkon KB, Stone JC, Van Parijs L, Lim B: Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity. 2003 Aug;19(2):243-55. doi: 10.1016/s1074-7613(03)00209-7. [PubMed:12932358 ]
  10. Authors unspecified: Retraction. Autoimmunity as the consequence of a spontaneous mutation in Rasgrp1. Immunity. 2012 May 25;36(5):886. doi: 10.1016/j.immuni.2012.05.007. [PubMed:22808526 ]
  11. Rambaratsingh RA, Stone JC, Blumberg PM, Lorenzo PS: RasGRP1 represents a novel non-protein kinase C phorbol ester signaling pathway in mouse epidermal keratinocytes. J Biol Chem. 2003 Dec 26;278(52):52792-801. doi: 10.1074/jbc.M308240200. Epub 2003 Oct 7. [PubMed:14532295 ]
  12. Norment AM, Bogatzki LY, Klinger M, Ojala EW, Bevan MJ, Kay RJ: Transgenic expression of RasGRP1 induces the maturation of double-negative thymocytes and enhances the production of CD8 single-positive thymocytes. J Immunol. 2003 Feb 1;170(3):1141-9. doi: 10.4049/jimmunol.170.3.1141. [PubMed:12538669 ]