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Gene Review

Rapgef1  -  Rap guanine nucleotide exchange factor...

Mus musculus

Synonyms: 4932418O06Rik, C3G, Grf2
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Disease relevance of Rapgef1

  • Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice [1].
  • At the highest doses of C3G and Mirtoselect adenoma numbers were decreased by 45% (p < 0.001) or 30% (p < 0.05), respectively, compared to controls [2].
  • The efficacy of C3G and Mirtoselect in the Apc(Min) mouse renders the further development of anthocyanins as potential human colorectal cancer chemopreventive agents worthwhile [2].

High impact information on Rapgef1


Biological context of Rapgef1


Anatomical context of Rapgef1

  • Adhesion-induced tyrosine phosphorylation of C3G is dependent on an intact cytoskeleton and peaks at 5-10 min after attachment [6].
  • Mouse Schwann cells (MSCs) express R-Ras and TC21/R-Ras2 and their specific guanine exchange factors, C3G and AND-34 [7].
  • Total anthocyanin levels in mice on C3G or Mirtoselect were 43 ng and 8.1 mug/g tissue, respectively, in the intestinal mucosa, and 7.2 and 12.3 mug/ml in the urine [2].
  • In the present study, we examined the effect of d-glucose (main substrate of SGLT1), phloridzin (inhibitor of SGLT1), and quercetin-3-glucose (Q3G, a flavonol) on the absorption of cyanidin-3-glucoside (C3G; approximately 5 micromol/L) by mouse jejunum mounted in Ussing chambers [8].
  • Disruption of flotillin-1-based domains prevents the activation of C3G, movement of GLUT4 to the sarcolemma, and glucose uptake in response to insulin [9].

Associations of Rapgef1 with chemical compounds

  • In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals [1].
  • We found that the presence of either D-glucose (10, 20, and 40 mmol/L) or phloridzin (50, 100, and 200 micromol/L) resulted in a small but insignificant inhibition of C3G disappearance from the mucosal solution (decrease of disappearance with glucose, 33%; with phloridzin, 18%; NS) [8].
  • However, when the flavonol Q3G (50 micromol/L) was added to the mucosal solution together with the C3G, the disappearance of C3G was significantly decreased (74%; p < 0.001), and Q3G disappeared instead [8].

Regulatory relationships of Rapgef1

  • C3G is activated in response to reelin in cortical neurons, which, in turn, leads to activation of the small GTPase Rap1 [10].

Other interactions of Rapgef1

  • These data indicate that GPCRs coupled to pertussis-toxin-sensitive G-proteins activate Rap through a Galpha subunit, C3G, and Src-dependent pathway [11].

Analytical, diagnostic and therapeutic context of Rapgef1

  • By RT-PCR analysis, it was found that these two types of C3G mRNA existed in all the mouse tissues [5].


  1. Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits chemopreventive and chemotherapeutic activity. Ding, M., Feng, R., Wang, S.Y., Bowman, L., Lu, Y., Qian, Y., Castranova, V., Jiang, B.H., Shi, X. J. Biol. Chem. (2006) [Pubmed]
  2. Effect of cyanidin-3-glucoside and an anthocyanin mixture from bilberry on adenoma development in the Apc(Min) mouse model of intestinal carcinogenesis-Relationship with tissue anthocyanin levels. Cooke, D., Schwarz, M., Boocock, D., Winterhalter, P., Steward, W.P., Gescher, A.J., Marczylo, T.H. Int. J. Cancer (2006) [Pubmed]
  3. The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation. Voss, A.K., Gruss, P., Thomas, T. Development (2003) [Pubmed]
  4. Activation of a Dab1/CrkL/C3G/Rap1 pathway in Reelin-stimulated neurons. Ballif, B.A., Arnaud, L., Arthur, W.T., Guris, D., Imamoto, A., Cooper, J.A. Curr. Biol. (2004) [Pubmed]
  5. C3G, a guanine nucleotide exchange factor bound to adapter molecule c-Crk, has two alternative splicing forms. Zhai, B., Huo, H., Liao, K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  6. C3G is tyrosine-phosphorylated after integrin-mediated cell adhesion in normal but not in Bcr/Abl expressing cells. de Jong, R., van Wijk, A., Heisterkamp, N., Groffen, J. Oncogene (1998) [Pubmed]
  7. Role of TC21/R-Ras2 in enhanced migration of neurofibromin-deficient Schwann cells. Huang, Y., Rangwala, F., Fulkerson, P.C., Ling, B., Reed, E., Cox, A.D., Kamholz, J., Ratner, N. Oncogene (2004) [Pubmed]
  8. The flavonol quercetin-3-glucoside inhibits cyanidin-3-glucoside absorption in vitro. Walton, M.C., McGhie, T.K., Reynolds, G.W., Hendriks, W.H. J. Agric. Food Chem. (2006) [Pubmed]
  9. Spatial and temporal regulation of GLUT4 translocation by flotillin-1 and caveolin-3 in skeletal muscle cells. Fecchi, K., Volonte, D., Hezel, M.P., Schmeck, K., Galbiati, F. FASEB J. (2006) [Pubmed]
  10. C3G regulates cortical neuron migration, preplate splitting and radial glial cell attachment. Voss, A.K., Britto, J.M., Dixon, M.P., Sheikh, B.N., Collin, C., Tan, S.S., Thomas, T. Development (2008) [Pubmed]
  11. G-protein-coupled receptor-mediated activation of rap GTPases: characterization of a novel Galphai regulated pathway. Weissman, J.T., Ma, J.N., Essex, A., Gao, Y., Burstein, E.S. Oncogene (2004) [Pubmed]
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