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Identification
HMDB Protein ID HMDBP07720
Secondary Accession Numbers
  • 13429
Name RAS guanyl-releasing protein 2
Synonyms
  1. CalDAG-GEFI
  2. Calcium and DAG-regulated guanine nucleotide exchange factor I
  3. Cdc25-like protein
  4. F25B3.3 kinase-like protein
  5. hCDC25L
Gene Name RASGRP2
Protein Type Unknown
Biological Properties
General Function Involved in calcium ion binding
Specific Function Functions as a calcium- and DAG-regulated nucleotide exchange factor specifically activating Rap through the exchange of bound GDP for GTP. May also activates other GTPases such as RRAS, RRAS2, NRAS, KRAS but not HRAS. Functions in aggregation of platelets and adhesion of T-lymphocytes and neutrophils probably through inside-out integrin activation. May function in the muscarinic acetylcholine receptor M1/CHRM1 signaling pathway
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. Peripheral membrane protein
  4. cytosol
  5. Peripheral membrane protein (Potential)
  6. Cell junction
  7. synapse
  8. Cell projection
  9. synaptosome (Potential)
  10. ruffle membrane
Gene Properties
Chromosome Location Chromosome:1
Locus 11q13
SNPs RASGRP2
Gene Sequence
>1830 bp
ATGGCAGGCACCCTGGACCTGGACAAGGGCTGCACGGTGGAGGAGCTGCTCCGCGGGTGC
ATCGAAGCCTTCGATGACTCCGGGAAGGTGCGGGACCCGCAGCTGGTGCGCATGTTCCTC
ATGATGCACCCCTGGTACATCCCCTCCTCTCAGCTGGCGGCCAAGCTGCTCCACATCTAC
CAACAATCCCGGAAGGACAACTCCAATTCCCTGCAGGTGAAAACGTGCCACCTGGTCAGG
TACTGGATCTCCGCCTTCCCAGCGGAGTTTGACTTGAACCCGGAGTTGGCTGAGCAGATC
AAGGAGCTGAAGGCTCTGCTAGACCAAGAAGGGAACCGACGGCACAGCAGCCTAATCGAC
ATAGACAGCGTCCCTACCTACAAGTGGAAGCGGCAGGTGACTCAGCGGAACCCTGTGGGA
CAGAAAAAGCGCAAGATGTCCCTGTTGTTTGACCACCTGGAGCCCATGGAGCTGGCGGAG
CATCTCACCTACTTGGAGTATCGCTCCTTCTGCAAGATCCTGTTTCAGGACTATCACAGT
TTCGTGACTCATGGCTGCACTGTGGACAACCCCGTCCTGGAGCGGTTCATCTCCCTCTTC
AACAGCGTCTCACAGTGGGTGCAGCTCATGATCCTCAGCAAACCCACAGCCCCGCAGCGG
GCCCTGGTCATCACACACTTTGTCCACGTGGCGGAGAAGCTGCTACAGCTGCAGAACTTC
AACACGCTGATGGCAGTGGTCGGGGGCCTGAGCCACAGCTCCATCTCCCGCCTCAAGGAG
ACCCACAGCCACGTTAGCCCTGAGACCATCAAGCTCTGGGAGGGTCTCACGGAACTAGTG
ACGGCGACAGGCAACTATGGCAACTACCGGCGTCGGCTGGCAGCCTGTGTGGGCTTCCGC
TTCCCGATCCTGGGTGTGCACCTCAAGGACCTGGTGGCCCTGCAGCTGGCACTGCCTGAC
TGGCTGGACCCAGCCCGGACCCGGCTCAACGGGGCCAAGATGAAGCAGCTCTTTAGCATC
CTGGAGGAGCTGGCCATGGTGACCAGCCTGCGGCCACCAGTACAGGCCAACCCCGACCTG
CTGAGCCTGCTCACGGTGTCTCTGGATCAGTATCAGACGGAGGATGAGCTGTACCAGCTG
TCCCTGCAGCGGGAGCCGCGCTCCAAGTCCTCGCCAACCAGCCCCACGAGTTGCACCCCA
CCACCCCGGCCCCCGGTACTGGAGGAGTGGACCTCGGCTGCCAAACCCAAGCTGGATCAG
GCCCTCGTGGTGGAGCACATCGAGAAGATGGTGGAGTCTGTGTTCCGGAACTTTGACGTC
GATGGGGATGGCCACATCTCACAGGAAGAATTCCAGATCATCCGTGGGAACTTCCCTTAC
CTCAGCGCCTTTGGGGACCTCGACCAGAACCAGGATGGCTGCATCAGCAGGGAGGAGATG
GTTTCCTATTTCCTGCGCTCCAGCTCTGTGTTGGGGGGGCGCATGGGCTTCGTACACAAC
TTCCAGGAGAGCAACTCCTTGCGCCCCGTCGCCTGCCGCCACTGCAAAGCCCTGATCCTG
GGCATCTACAAGCAGGGCCTCAAATGCCGAGCCTGTGGAGTGAACTGCCACAAGCAGTGC
AAGGATCGCCTGTCAGTTGAGTGTCGGCGCAGGGCCCAGAGTGTGAGCCTGGAGGGGTCT
GCACCCTCACCCTCACCCATGCACAGCCACCATCACCGCGCCTTCAGCTTCTCTCTGCCC
CGCCCTGGCAGGCGAGGCTCCAGGCCTCCAGAGATCCGTGAGGAGGAGGTACAGACGGTG
GAGGATGGGGTGTTTGACATCCACTTGTAA
Protein Properties
Number of Residues 609
Molecular Weight 69247.8
Theoretical pI 7.85
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>RAS guanyl-releasing protein 2
MAGTLDLDKGCTVEELLRGCIEAFDDSGKVRDPQLVRMFLMMHPWYIPSSQLAAKLLHIY
QQSRKDNSNSLQVKTCHLVRYWISAFPAEFDLNPELAEQIKELKALLDQEGNRRHSSLID
IDSVPTYKWKRQVTQRNPVGQKKRKMSLLFDHLEPMELAEHLTYLEYRSFCKILFQDYHS
FVTHGCTVDNPVLERFISLFNSVSQWVQLMILSKPTAPQRALVITHFVHVAEKLLQLQNF
NTLMAVVGGLSHSSISRLKETHSHVSPETIKLWEGLTELVTATGNYGNYRRRLAACVGFR
FPILGVHLKDLVALQLALPDWLDPARTRLNGAKMKQLFSILEELAMVTSLRPPVQANPDL
LSLLTVSLDQYQTEDELYQLSLQREPRSKSSPTSPTSCTPPPRPPVLEEWTSAAKPKLDQ
ALVVEHIEKMVESVFRNFDVDGDGHISQEEFQIIRGNFPYLSAFGDLDQNQDGCISREEM
VSYFLRSSSVLGGRMGFVHNFQESNSLRPVACRHCKALILGIYKQGLKCRACGVNCHKQC
KDRLSVECRRRAQSVSLEGSAPSPSPMHSHHHRAFSFSLPRPGRRGSRPPEIREEEVQTV
EDGVFDIHL
GenBank ID Protein 149158727
UniProtKB/Swiss-Prot ID Q7LDG7
UniProtKB/Swiss-Prot Entry Name GRP2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001098670.1
GeneCard ID RASGRP2
GenAtlas ID RASGRP2
HGNC ID HGNC:9879
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. 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 ]
  3. Kedra D, Seroussi E, Fransson I, Trifunovic J, Clark M, Lagercrantz J, Blennow E, Mehlin H, Dumanski J: The germinal center kinase gene and a novel CDC25-like gene are located in the vicinity of the PYGM gene on 11q13. Hum Genet. 1997 Oct;100(5-6):611-9. [PubMed:9341881 ]
  4. Clyde-Smith J, Silins G, Gartside M, Grimmond S, Etheridge M, Apolloni A, Hayward N, Hancock JF: Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor. J Biol Chem. 2000 Oct 13;275(41):32260-7. [PubMed:10918068 ]
  5. Dupuy AJ, Morgan K, von Lintig FC, Shen H, Acar H, Hasz DE, Jenkins NA, Copeland NG, Boss GR, Largaespada DA: Activation of the Rap1 guanine nucleotide exchange gene, CalDAG-GEF I, in BXH-2 murine myeloid leukemia. J Biol Chem. 2001 Apr 13;276(15):11804-11. Epub 2001 Jan 22. [PubMed:11278453 ]
  6. 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. 2004 Mar 19;279(12):11875-81. Epub 2003 Dec 31. [PubMed:14702343 ]
  7. Caloca MJ, Zugaza JL, Vicente-Manzanares M, Sanchez-Madrid F, Bustelo XR: F-actin-dependent translocation of the Rap1 GDP/GTP exchange factor RasGRP2. J Biol Chem. 2004 May 7;279(19):20435-46. Epub 2004 Feb 26. [PubMed:14988412 ]
  8. Ghandour H, Cullere X, Alvarez A, Luscinskas FW, Mayadas TN: Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood. 2007 Nov 15;110(10):3682-90. Epub 2007 Aug 16. [PubMed:17702895 ]
  9. Pasvolsky R, Feigelson SW, Kilic SS, Simon AJ, Tal-Lapidot G, Grabovsky V, Crittenden JR, Amariglio N, Safran M, Graybiel AM, Rechavi G, Ben-Dor S, Etzioni A, Alon R: A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets. J Exp Med. 2007 Jul 9;204(7):1571-82. Epub 2007 Jun 18. [PubMed:17576779 ]
  10. Kuijpers TW, van de Vijver E, Weterman MA, de Boer M, Tool AT, van den Berg TK, Moser M, Jakobs ME, Seeger K, Sanal O, Unal S, Cetin M, Roos D, Verhoeven AJ, Baas F: LAD-1/variant syndrome is caused by mutations in FERMT3. Blood. 2009 May 7;113(19):4740-6. doi: 10.1182/blood-2008-10-182154. Epub 2008 Dec 8. [PubMed:19064721 ]
  11. Svensson L, Howarth K, McDowall A, Patzak I, Evans R, Ussar S, Moser M, Metin A, Fried M, Tomlinson I, Hogg N: Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat Med. 2009 Mar;15(3):306-12. doi: 10.1038/nm.1931. Epub 2009 Feb 22. [PubMed:19234463 ]
  12. Malinin NL, Zhang L, Choi J, Ciocea A, Razorenova O, Ma YQ, Podrez EA, Tosi M, Lennon DP, Caplan AI, Shurin SB, Plow EF, Byzova TV: A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans. Nat Med. 2009 Mar;15(3):313-8. doi: 10.1038/nm.1917. Epub 2009 Feb 22. [PubMed:19234460 ]