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Rap guanine nucleotide exchange factor (GEF) 1
Symbols RAPGEF1 ; C3G; GRF2
External IDs OMIM600303 HomoloGene50501 GeneCards: RAPGEF1 Gene
RNA expression pattern
PBB GE RAPGEF1 204543 at tn.png
More reference expression data
Species Human Mouse
Entrez 2889 107746
Ensembl ENSG00000107263 ENSMUSG00000039844
UniProt Q13905 Q3UGX8
RefSeq (mRNA) NM_001304275 NM_001039086
RefSeq (protein) NP_001291204 NP_001034175
Location (UCSC) Chr 9:
131.58 – 131.74 Mb
Chr 2:
29.62 – 29.74 Mb
PubMed search [1] [2]

Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the RAPGEF1 gene.[1][2]

The protein encoded by this gene is a human guanine nucleotide releasing protein for Ras protein. It belongs to the adaptor-type Src homology (SH)2-containing molecules. Src homology 2 domains are globular protein modules present in a large variety of functionally distinct proteins. They mediate binding events that control the activity and localization of many proteins involved in the transmission of signals from the cell surface to the nucleus. The mRNAs of these proteins are expressed ubiquitously in human adult and fetal tissues. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined.[3]


RAPGEF1 has been shown to interact with BCAR1,[4] Grb2,[2][5] HCK,[6] CRKL[5][7][8][9][10][11][12] and CRK.[2]


  1. ^ Takai S, Tanaka M, Sugimura H, Yamada K, Naito Y, Kino I, Matsuda M (Dec 1994). "Mapping of the human C3G gene coding a guanine nucleotide releasing protein for Ras family to 9q34.3 by fluorescence in situ hybridization". Hum Genet 94 (5): 549–50. doi:10.1007/bf00211024. PMID 7959692. 
  2. ^ a b c Tanaka S, Morishita T, Hashimoto Y, Hattori S, Nakamura S, Shibuya M, Matuoka K, Takenawa T, Kurata T, Nagashima K et al. (May 1994). "C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins". Proc Natl Acad Sci U S A 91 (8): 3443–7. doi:10.1073/pnas.91.8.3443. PMC 43593. PMID 7512734. 
  3. ^ "Entrez Gene: RAPGEF1 Rap guanine nucleotide exchange factor (GEF) 1". 
  4. ^ Kirsch, K H; Georgescu M M; Hanafusa H (October 1998). "Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G". J. Biol. Chem. (UNITED STATES) 273 (40): 25673–9. doi:10.1074/jbc.273.40.25673. ISSN 0021-9258. PMID 9748234. 
  5. ^ a b Smit, L; van der Horst G; Borst J (April 1996). "Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors". J. Biol. Chem. (UNITED STATES) 271 (15): 8564–9. doi:10.1074/jbc.271.15.8564. ISSN 0021-9258. PMID 8621483. 
  6. ^ Shivakrupa, R; Radha Vegesna; Sudhakar Ch; Swarup Ghanshyam (Dec 2003). "Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain". J. Biol. Chem. (United States) 278 (52): 52188–94. doi:10.1074/jbc.M310656200. ISSN 0021-9258. PMID 14551197. 
  7. ^ Kyono, W T; de Jong R; Park R K; Liu Y; Heisterkamp N; Groffen J; Durden D L (November 1998). "Differential interaction of Crkl with Cbl or C3G, Hef-1, and gamma subunit immunoreceptor tyrosine-based activation motif in signaling of myeloid high affinity Fc receptor for IgG (Fc gamma RI)". J. Immunol. (UNITED STATES) 161 (10): 5555–63. ISSN 0022-1767. PMID 9820532. 
  8. ^ Grumbach, I M; Mayer I A; Uddin S; Lekmine F; Majchrzak B; Yamauchi H; Fujita S; Druker B; Fish E N; Platanias L C (February 2001). "Engagement of the CrkL adaptor in interferon alpha signalling in BCR-ABL-expressing cells". Br. J. Haematol. (England) 112 (2): 327–36. doi:10.1046/j.1365-2141.2001.02556.x. ISSN 0007-1048. PMID 11167825. 
  9. ^ Ahmad, S; Alsayed Y M; Druker B J; Platanias L C (November 1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein". J. Biol. Chem. (UNITED STATES) 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. ISSN 0021-9258. PMID 9374471. 
  10. ^ Chin, H; Saito T; Arai A; Yamamoto K; Kamiyama R; Miyasaka N; Miura O (October 1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochem. Biophys. Res. Commun. (UNITED STATES) 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. ISSN 0006-291X. PMID 9344843. 
  11. ^ Wu, C; Lai C F; Mobley W C (August 2001). "Nerve growth factor activates persistent Rap1 signaling in endosomes". J. Neurosci. (United States) 21 (15): 5406–16. PMID 11466412. 
  12. ^ Sakkab, D; Lewitzky M; Posern G; Schaeper U; Sachs M; Birchmeier W; Feller S M (April 2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. (UNITED STATES) 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. ISSN 0021-9258. PMID 10753869. 

Further reading[edit]

  • Pessin JE, Okada S (2002). "Insulin and EGF receptors integrate the Ras and Rap signaling pathways.". Endocr. J. 46 Suppl: S11–6. doi:10.1507/endocrj.46.suppl_s11. PMID 12054111. 
  • Ehrhardt A, Ehrhardt GR, Guo X, Schrader JW (2002). "Ras and relatives--job sharing and networking keep an old family together.". Exp. Hematol. 30 (10): 1089–106. doi:10.1016/S0301-472X(02)00904-9. PMID 12384139. 
  • Knudsen BS, Feller SM, Hanafusa H (1995). "Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk.". J. Biol. Chem. 269 (52): 32781–7. PMID 7806500. 
  • Gotoh T, Hattori S, Nakamura S et al. (1996). "Identification of Rap1 as a target for the Crk SH3 domain-binding guanine nucleotide-releasing factor C3G.". Mol. Cell. Biol. 15 (12): 6746–53. PMC 230928. PMID 8524240. 
  • Smit L, van der Horst G, Borst J (1996). "Sos, Vav, and C3G participate in B cell receptor-induced signaling pathways and differentially associate with Shc-Grb2, Crk, and Crk-L adaptors.". J. Biol. Chem. 271 (15): 8564–9. doi:10.1074/jbc.271.15.8564. PMID 8621483. 
  • Matsuda M, Ota S, Tanimura R et al. (1996). "Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins.". J. Biol. Chem. 271 (24): 14468–72. doi:10.1074/jbc.271.24.14468. PMID 8662907. 
  • Uemura N, Salgia R, Li JL et al. (1997). "The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins.". Leukemia 11 (3): 376–85. doi:10.1038/sj.leu.2400590. PMID 9067577. 
  • Husson H, Mograbi B, Schmid-Antomarchi H et al. (1997). "CSF-1 stimulation induces the formation of a multiprotein complex including CSF-1 receptor, c-Cbl, PI 3-kinase, Crk-II and Grb2.". Oncogene 14 (19): 2331–8. doi:10.1038/sj.onc.1201074. PMID 9178909. 
  • Chin H, Saito T, Arai A et al. (1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells.". Biochem. Biophys. Res. Commun. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID 9344843. 
  • Ahmad S, Alsayed YM, Druker BJ, Platanias LC (1997). "The type I interferon receptor mediates tyrosine phosphorylation of the CrkL adaptor protein.". J. Biol. Chem. 272 (48): 29991–4. doi:10.1074/jbc.272.48.29991. PMID 9374471. 
  • Guerrero C, Fernandez-Medarde A, Rojas JM et al. (1998). "Transformation suppressor activity of C3G is independent of its CDC25-homology domain.". Oncogene 16 (5): 613–24. doi:10.1038/sj.onc.1201569. PMID 9482107. 
  • Ohashi Y, Tachibana K, Kamiguchi K et al. (1998). "T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G.". J. Biol. Chem. 273 (11): 6446–51. doi:10.1074/jbc.273.11.6446. PMID 9497377. 
  • Astier A, Manié SN, Law SF et al. (1998). "Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: potential relevance to neoplastic lymphohematopoietic cells.". Leuk. Lymphoma 28 (1-2): 65–72. doi:10.3109/10428199709058332. PMID 9498705. 
  • Yokote K, Hellman U, Ekman S et al. (1998). "Identification of Tyr-762 in the platelet-derived growth factor alpha-receptor as the binding site for Crk proteins.". Oncogene 16 (10): 1229–39. doi:10.1038/sj.onc.1201641. PMID 9546424. 
  • Kirsch KH, Georgescu MM, Hanafusa H (1998). "Direct binding of p130(Cas) to the guanine nucleotide exchange factor C3G.". J. Biol. Chem. 273 (40): 25673–9. doi:10.1074/jbc.273.40.25673. PMID 9748234. 
  • Ichiba T, Hashimoto Y, Nakaya M et al. (1999). "Activation of C3G guanine nucleotide exchange factor for Rap1 by phosphorylation of tyrosine 504.". J. Biol. Chem. 274 (20): 14376–81. doi:10.1074/jbc.274.20.14376. PMID 10318861. 
  • Nosaka Y, Arai A, Miyasaka N, Miura O (1999). "CrkL mediates Ras-dependent activation of the Raf/ERK pathway through the guanine nucleotide exchange factor C3G in hematopoietic cells stimulated with erythropoietin or interleukin-3.". J. Biol. Chem. 274 (42): 30154–62. doi:10.1074/jbc.274.42.30154. PMID 10514505. 
  • Uemura N, Griffin JD (2000). "The adapter protein Crkl links Cbl to C3G after integrin ligation and enhances cell migration.". J. Biol. Chem. 274 (53): 37525–32. doi:10.1074/jbc.274.53.37525. PMID 10608804. 

External links[edit]