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Identification
HMDB Protein ID HMDBP07719
Secondary Accession Numbers
  • 13428
Name RAS guanyl-releasing protein 1
Synonyms
  1. CalDAG-GEFII
  2. Calcium and DAG-regulated guanine nucleotide exchange factor II
  3. Ras guanyl-releasing protein
Gene Name RASGRP1
Protein Type Unknown
Biological Properties
General Function Involved in calcium ion binding
Specific Function Functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor specifically activating Ras through the exchange of bound GDP for GTP. Activates the Erk/MAP kinase cascade. Couples T-lymphocytes and B-lymphocytes antigen receptors to the activation of Ras. Hence, regulates T-cells and B-cells development, homeostasis and differentiation. Functions also in FcERI-evoked degranulation and cytokine secretion by mast cells, regulating allergic responses. May also function in other cell types differentiation
Pathways Not Available
Reactions Not Available
GO Classification
Component
cell part
intracellular
Function
ion binding
cation binding
metal ion binding
binding
enzyme regulator activity
nucleoside-triphosphatase regulator activity
gtpase regulator activity
guanyl-nucleotide exchange factor activity
calcium ion binding
Process
biological regulation
regulation of biological process
regulation of cellular process
signal transduction
intracellular signaling pathway
signaling
signaling pathway
intracellular signal transduction
small gtpase mediated signal transduction
regulation of cell communication
regulation of signal transduction
regulation of small gtpase mediated signal transduction
Cellular Location
  1. Cell membrane
  2. Cytoplasm
  3. Golgi apparatus membrane
  4. Peripheral membrane protein
  5. Peripheral membrane protein
  6. Peripheral membrane protein
  7. Endoplasmic reticulum membrane
  8. cytosol
Gene Properties
Chromosome Location Chromosome:1
Locus 15q14
SNPs RASGRP1
Gene Sequence
>2394 bp
ATGGGCACCCTGGGCAAGGCGAGAGAGGCTCCGCGGAAACCTTCCCATGGCTGCAGAGCT
GCCTCTAAAGCAAGACTAGAGGCAAAGCCAGCCAACAGCCCCTTCCCCTCCCATCCCAGC
TTGGCCCACATCACCCAGTTCCGAATGATGGTGTCTCTGGGACATTTAGCCAAAGGAGCC
AGCCTGGACGATCTCATTGACAGCTGCATTCAATCTTTTGATGCAGATGGAAACCTGTGT
CGAAGTAACCAACTGTTGCAAGTCATGCTGACCATGCACCGAATTGTCATCTCCTCTGCA
GAACTGCTCCAAAAAGTTATCACCCTCTATAAGGATGCTTTGGCAAAGAATTCACCAGGA
CTTTGCCTGAAGATCTGTTATTTTGTAAGGTATTGGATAACAGAATTCTGGGTCATGTTT
AAAATGGACGCCAGCTTGACAGACACTATGGAGGAGTTTCAGGAACTGGTGAAAGCTAAG
GGTGAGGAGTTACATTGCCGCCTGATTGACACAACTCAAATCAATGCCCGTGACTGGTCC
AGGAAACTTACTCAAAGGATAAAATCAAATACCAGCAAGAAACGGAAAGTCTCCCTGCTC
TTTGACCATCTGGAACCAGAAGAGCTATCCGAGCACCTCACCTACCTTGAGTTCAAGTCT
TTCCGGAGGATATCGTTCTCTGATTATCAGAATTACCTTGTAAATAGCTGTGTGAAGGAA
AACCCCACCATGGAGCGATCTATTGCTCTGTGCAACGGCATCTCCCAGTGGGTACAACTG
ATGGTTCTCAGCCGCCCCACGCCGCAGCTCCGAGCAGAAGTCTTCATCAAGTTCATCCAG
GTGGCTCAGAAGCTCCACCAACTACAGAACTTCAATACACTGATGGCTGTGATAGGTGGG
CTGTGTCACAGCTCAATCTCGAGGCTCAAGGAGACAAGTTCGCATGTCCCACATGAAATC
AATAAGGTTCTCGGTGAGATGACTGAGCTGCTGTCCTCCTCCAGAAACTACGACAATTAC
CGGCGAGCCTATGGAGAGTGCACCGACTTCAAGATCCCCATTCTGGGTGTGCATCTCAAG
GACCTCATCTCCCTGTATGAAGCCATGCCTGACTATCTGGAGGACGGGAAAGTGAACGTC
CATAAGCTACTGGCCCTATACAATCATATCAGTGAATTGGTCCAGCTGCAAGAGGTGGCC
CCACCCTTGGAGGCTAACAAGGACTTGGTACACTTGCTGACGTTATCCCTGGATCTTTAC
TACACTGAGGATGAAATCTATGAGCTTTCCTATGCCCGGGAACCAAGGAACCACAGAGCT
CCACCACTAACACCTTCAAAGCCACCAGTAGTAGTGGACTGGGCTTCTGGAGTGTCTCCC
AAACCTGATCCAAAAACCATTAGCAAACACGTCCAGAGGATGGTGGATTCTGTCTTCAAG
AACTATGATCACGACCAGGATGGATACATTTCTCAGGAAGAATTTGAAAAGATTGCTGCG
AGTTTTCCATTTTCCTTCTGTGTGATGGACAAAGACAGGGAAGGCCTCATCAGCAGGGAT
GAGATCACAGCCTACTTCATGAGAGCCAGCTCAATCTATTCCAAGCTGGGCCTGGGCTTT
CCTCACAACTTCCAAGAGACCACCTACCTGAAGCCCACTTTTTGTGACAACTGTGCTGGA
TTTCTCTGGGGAGTGATCAAACAAGGATATCGATGTAAAGACTGCGGGATGAACTGTCAC
AAACAATGCAAAGATCTGGTTGTGTTTGAGTGTAAGAAGCGAGCCAAGAACCCAGTAGCT
CCCACAGAGAACAACACTTCTGTGGGGCCAGTGTCCAACCTTTGCTCATTGGGAGCCAAA
GATCTGCTCCATGCACCTGAGGAAGGACCTTTTACATTCCCTAATGGGGAGGCTGTGGAA
CATGGTGAGGAGAGTAAGGATCGGACCATCATGCTGATGGGAGTGTCCTCACAGAAGATT
TCTCTTCGGCTGAAGAGGGCTGTTGCCCACAAGGCCACCCAGACTGAATCACAGCCTTGG
ATTGGCAGTGAGGGCCCTTCAGGTCCCTTTGTGCTGTCTTCCCCAAGGAAGACAGCCCAG
GATACTCTATATGTGCTTCCCAGTCCCACCTCTCCATGTCCTAGCCCAGTCTTGGTCAGA
AAGCGGGCTTTTGTCAAGTGGGAGAATAAAGACTCCCTCATAAAATCAAAGGAGGAGCTC
CGTCACCTCAGACTGCCTACCTACCAAGAACTGGAACAGGAAATAAATACTCTGAAAGCA
GATAATGATGCCCTAAAGATCCAACTGAAATATGCACAGAAGAAAATAGAATCCCTCCAG
CTTGAAAAAAGCAATCATGTCTTAGCTCAAATGGAGCAGGGTGACTGTTCTTAG
Protein Properties
Number of Residues 797
Molecular Weight 90401.0
Theoretical pI 8.02
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>RAS guanyl-releasing protein 1
MGTLGKAREAPRKPSHGCRAASKARLEAKPANSPFPSHPSLAHITQFRMMVSLGHLAKGA
SLDDLIDSCIQSFDADGNLCRSNQLLQVMLTMHRIVISSAELLQKVITLYKDALAKNSPG
LCLKICYFVRYWITEFWVMFKMDASLTDTMEEFQELVKAKGEELHCRLIDTTQINARDWS
RKLTQRIKSNTSKKRKVSLLFDHLEPEELSEHLTYLEFKSFRRISFSDYQNYLVNSCVKE
NPTMERSIALCNGISQWVQLMVLSRPTPQLRAEVFIKFIQVAQKLHQLQNFNTLMAVIGG
LCHSSISRLKETSSHVPHEINKVLGEMTELLSSSRNYDNYRRAYGECTDFKIPILGVHLK
DLISLYEAMPDYLEDGKVNVHKLLALYNHISELVQLQEVAPPLEANKDLVHLLTLSLDLY
YTEDEIYELSYAREPRNHRAPPLTPSKPPVVVDWASGVSPKPDPKTISKHVQRMVDSVFK
NYDHDQDGYISQEEFEKIAASFPFSFCVMDKDREGLISRDEITAYFMRASSIYSKLGLGF
PHNFQETTYLKPTFCDNCAGFLWGVIKQGYRCKDCGMNCHKQCKDLVVFECKKRAKNPVA
PTENNTSVGPVSNLCSLGAKDLLHAPEEGPFTFPNGEAVEHGEESKDRTIMLMGVSSQKI
SLRLKRAVAHKATQTESQPWIGSEGPSGPFVLSSPRKTAQDTLYVLPSPTSPCPSPVLVR
KRAFVKWENKDSLIKSKEELRHLRLPTYQELEQEINTLKADNDALKIQLKYAQKKIESLQ
LEKSNHVLAQMEQGDCS
GenBank ID Protein 190684644
UniProtKB/Swiss-Prot ID O95267
UniProtKB/Swiss-Prot Entry Name GRP1_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_005739.3
GeneCard ID RASGRP1
GenAtlas ID RASGRP1
HGNC ID HGNC:9878
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  3. Topham MK, Prescott SM: Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism. J Cell Biol. 2001 Mar 19;152(6):1135-43. [PubMed:11257115 ]
  4. 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. 1998 Oct 27;95(22):13278-83. [PubMed:9789079 ]
  5. 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 ]
  6. Yasuda S, Stevens RL, Terada T, Takeda M, Hashimoto T, Fukae J, Horita T, Kataoka H, Atsumi T, Koike T: Defective expression of Ras guanyl nucleotide-releasing protein 1 in a subset of patients with systemic lupus erythematosus. J Immunol. 2007 Oct 1;179(7):4890-900. [PubMed:17878389 ]
  7. Ebinu JO, Stang SL, Teixeira C, Bottorff DA, Hooton J, Blumberg PM, Barry M, Bleakley RC, Ostergaard HL, Stone JC: RasGRP links T-cell receptor signaling to Ras. Blood. 2000 May 15;95(10):3199-203. [PubMed:10807788 ]
  8. Jones DR, Sanjuan MA, Stone JC, Merida I: Expression of a catalytically inactive form of diacylglycerol kinase alpha induces sustained signaling through RasGRP. FASEB J. 2002 Apr;16(6):595-7. [PubMed:11919165 ]
  9. Caloca MJ, Zugaza JL, Matallanas D, Crespo P, Bustelo XR: Vav mediates Ras stimulation by direct activation of the GDP/GTP exchange factor Ras GRP1. EMBO J. 2003 Jul 1;22(13):3326-36. [PubMed:12839994 ]
  10. Caloca MJ, Zugaza JL, Bustelo XR: Exchange factors of the RasGRP family mediate Ras activation in the Golgi. J Biol Chem. 2003 Aug 29;278(35):33465-73. Epub 2003 Jun 2. [PubMed:12782630 ]
  11. 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 ]
  12. Perez de Castro I, Bivona TG, Philips MR, Pellicer A: Ras activation in Jurkat T cells following low-grade stimulation of the T-cell receptor is specific to N-Ras and occurs only on the Golgi apparatus. Mol Cell Biol. 2004 Apr;24(8):3485-96. [PubMed:15060167 ]
  13. Zugaza JL, Caloca MJ, Bustelo XR: Inverted signaling hierarchy between RAS and RAC in T-lymphocytes. Oncogene. 2004 Jul 29;23(34):5823-33. [PubMed:15184873 ]
  14. Zheng Y, Liu H, Coughlin J, Zheng J, Li L, Stone JC: Phosphorylation of RasGRP3 on threonine 133 provides a mechanistic link between PKC and Ras signaling systems in B cells. Blood. 2005 May 1;105(9):3648-54. Epub 2005 Jan 18. [PubMed:15657177 ]
  15. Roose JP, Mollenauer M, Gupta VA, Stone J, Weiss A: A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells. Mol Cell Biol. 2005 Jun;25(11):4426-41. [PubMed:15899849 ]
  16. Kosco KA, Cerignoli F, Williams S, Abraham RT, Mustelin T: SKAP55 modulates T cell antigen receptor-induced activation of the Ras-Erk-AP1 pathway by binding RasGRP1. Mol Immunol. 2008 Jan;45(2):510-22. Epub 2007 Jul 20. [PubMed:17658605 ]