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Gene Review

Rap1a  -  RAS-related protein-1a

Mus musculus

Synonyms: AI848598, G-22K, Krev-1, Rap1, Ras-related protein Krev-1, ...
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Disease relevance of Rap1a


High impact information on Rap1a

  • In Krev-1 transfectants, there is a correlation between the levels of specific mRNA and the degrees of suppression of the transformed phenotype [2].
  • Kirsten-ras-revertant 1 (Krev-1) cDNA encodes a ras-related protein and exhibits an activity of inducing flat revertants at certain frequencies (2-5% of total transfectants) when introduced into a v-K-ras-transformed mouse NIH 3T3 cell line, DT [1].
  • These findings are consistent with the idea that Krev-1 protein is regulated like many other G proteins by the guanine triphosphate/guanine diphosphate-exchange mechanism probably in response to certain negative growth-regulatory signals [1].
  • Microinjection of smg/rap1/Krev-1 p21 into Swiss 3T3 cells induces DNA synthesis and morphological changes [4].
  • The Krev-1 gene has been shown to suppress ras-mediated transformation in vitro [5].

Associations of Rap1a with chemical compounds


Biological context of Rap1a

  • Rap1a-rs1, which was not localized, has a sequence very similar to the Rap1a cDNA, suggesting that it has been recently acquired by the mouse genome [8].
  • smg/rap1/Krev-1 p21s inhibit the signal pathway to the c-fos promoter/enhancer from c-Ki-ras p21 but not from c-raf-1 kinase in NIH3T3 cells [9].

Anatomical context of Rap1a


Regulatory relationships of Rap1a

  • smg/rap1A/Krev-1 p21 cDNA is known to inhibit v-Ki-ras p21-induced cell transformation in NIH3T3 cells, but the inhibitory mechanism is not clear at present [9].

Other interactions of Rap1a

  • In this study, five amino acid residues flanking the ras effector domain, which are not conserved with the Krev-1 protein, were shown to be required for normal protein-protein interactions and biological activity [5].
  • The levels of PEA3 and PEG-3 RNA and proteins are elevated in the oncogenically transformed CREF cells, and reduced in transformation and tumorigenic suppressed Ha-ras/Krev-1 doubly transformed CREF cells [11].


  1. Genetic analysis of the Kirsten-ras-revertant 1 gene: potentiation of its tumor suppressor activity by specific point mutations. Kitayama, H., Matsuzaki, T., Ikawa, Y., Noda, M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. A ras-related gene with transformation suppressor activity. Kitayama, H., Sugimoto, Y., Matsuzaki, T., Ikawa, Y., Noda, M. Cell (1989) [Pubmed]
  3. Partial suppression of tumorigenicity in a human lung cancer cell line transfected with Krev-1. Caamano, J., DiRado, M., Iizasa, T., Momiki, S., Fernandes, E., Ashendel, C., Noda, M., Klein-Szanto, A.J. Mol. Carcinog. (1992) [Pubmed]
  4. Microinjection of smg/rap1/Krev-1 p21 into Swiss 3T3 cells induces DNA synthesis and morphological changes. Yoshida, Y., Kawata, M., Miura, Y., Musha, T., Sasaki, T., Kikuchi, A., Takai, Y. Mol. Cell. Biol. (1992) [Pubmed]
  5. Identification of amino acid residues required for Ras p21 target activation. Marshall, M.S., Davis, L.J., Keys, R.D., Mosser, S.D., Hill, W.S., Scolnick, E.M., Gibbs, J.B. Mol. Cell. Biol. (1991) [Pubmed]
  6. Rap1a null mice have altered myeloid cell functions suggesting distinct roles for the closely related Rap1a and 1b proteins. Li, Y., Yan, J., De, P., Chang, H.C., Yamauchi, A., Christopherson, K.W., Paranavitana, N.C., Peng, X., Kim, C., Munugalavadla, V., Munugulavadla, V., Kapur, R., Chen, H., Shou, W., Stone, J.C., Kaplan, M.H., Dinauer, M.C., Durden, D.L., Quilliam, L.A. J. Immunol. (2007) [Pubmed]
  7. Rap1 activation plays a regulatory role in pancreatic amylase secretion. Sabbatini, M.E., Chen, X., Ernst, S.A., Williams, J.A. J. Biol. Chem. (2008) [Pubmed]
  8. Organization and chromosomal locations of Rap1a/Krev sequences in the mouse. Dower, N.A., Seldin, M.F., Pugh, S., Stone, J.C. Mamm. Genome (1992) [Pubmed]
  9. smg/rap1/Krev-1 p21s inhibit the signal pathway to the c-fos promoter/enhancer from c-Ki-ras p21 but not from c-raf-1 kinase in NIH3T3 cells. Sakoda, T., Kaibuchi, K., Kishi, K., Kishida, S., Doi, K., Hoshino, M., Hattori, S., Takai, Y. Oncogene (1992) [Pubmed]
  10. Association of Rap1a and Rap1b proteins with late endocytic/phagocytic compartments and Rap2a with the Golgi complex. Pizon, V., Desjardins, M., Bucci, C., Parton, R.G., Zerial, M. J. Cell. Sci. (1994) [Pubmed]
  11. PEA3 sites within the progression elevated gene-3 (PEG-3) promoter and mitogen-activated protein kinase contribute to differential PEG-3 expression in Ha-ras and v-raf oncogene transformed rat embryo cells. Su, Z., Shi, Y., Friedman, R., Qiao, L., McKinstry, R., Hinman, D., Dent, P., Fisher, P.B. Nucleic Acids Res. (2001) [Pubmed]
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