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Gene Review

RAP1GAP  -  RAP1 GTPase activating protein

Homo sapiens

Synonyms: KIAA0474, RAP1GA1, RAP1GAP1, RAP1GAPII, RAPGAP, ...
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Disease relevance of RAP1GAP


High impact information on RAP1GAP

  • Thus, the alpha-subunit of G(i) activates the Ras-ERK/MAPK mitogenic pathway by membrane recruitment of rap1GAPII and reduction of GTP-bound Rap1 [6].
  • Here we show that a novel isoform of Rapl GTPase-activating protein, called rap1GAPII, binds specifically to the alpha-subunits of the G(i) family of heterotrimeric G-proteins [6].
  • Stimulation of the G(i)-coupled m2-muscarinic receptor translocates rap1GAPII from the cytosol to the membrane and decreases the amount of GTP-bound Rap1 [6].
  • Both the cAMP effect and the Epac effect on cell adhesion were abolished by the expression of Rap1-GTPase-activating protein, indicating the involvement of Rap1 in the signaling pathway [7].
  • We could detect mRNAs for a new protein most closely related to Rap1GAP and for postsynaptic density-95 discs-large and zona occludens protein 1 (PDZ)-GEF1 and CalDAG-GEFs I and III [8].

Biological context of RAP1GAP


Anatomical context of RAP1GAP


Associations of RAP1GAP with chemical compounds


Regulatory relationships of RAP1GAP


Other interactions of RAP1GAP

  • However, overexpression of a RAP1 GTPase-activating protein (RAP1GAP), which efficiently clamped cellular RAP1 in the inactive GDP-bound form, did not affect A(2A)-agonist-mediated MAP kinase stimulation [17].
  • In the present study, we showed that SPA-1, a Rap1 GTPase-activating protein (GAP), was bound to a cytoskeleton-anchoring protein AF-6 [18].
  • Human genomic clones, which hybridized with both mouse and human SIPA1 cDNA but not with RAP1GAP cDNA, were then isolated [19].
  • However, in rap1GAPII-expressing cells, ephrin-B1 did not induce membrane spreading, probably due to instability of the focal complex [20].
  • Our results suggest that CD28-mediated Rap1 GTPase-activating protein activation can help explain the augmentation of ERKs during CD28 costimulation [21].

Analytical, diagnostic and therapeutic context of RAP1GAP


  1. Rap1GAP inhibits tumor growth in oropharyngeal squamous cell carcinoma. Zhang, Z., Mitra, R.S., Henson, B.S., Datta, N.S., McCauley, L.K., Kumar, P., Lee, J.S., Carey, T.E., D'Silva, N.J. Am. J. Pathol. (2006) [Pubmed]
  2. Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. Zhang, L., Chenwei, L., Mahmood, R., van Golen, K., Greenson, J., Li, G., D'Silva, N.J., Li, X., Burant, C.F., Logsdon, C.D., Simeone, D.M. Cancer Res. (2006) [Pubmed]
  3. Rap-specific GTPase activating protein follows an alternative mechanism. Brinkmann, T., Daumke, O., Herbrand, U., Kühlmann, D., Stege, P., Ahmadian, M.R., Wittinghofer, A. J. Biol. Chem. (2002) [Pubmed]
  4. Local activation of Rap1 contributes to directional vascular endothelial cell migration accompanied by extension of microtubules on which RAPL, a Rap1-associating molecule, localizes. Fujita, H., Fukuhara, S., Sakurai, A., Yamagishi, A., Kamioka, Y., Nakaoka, Y., Masuda, M., Mochizuki, N. J. Biol. Chem. (2005) [Pubmed]
  5. Clinicopathological and prognostic relevance of Rap1-GAP expression in melanocytic tumors. Weiss, J., Biwer, B., Schliz, M., Jung, E.G. Arch. Dermatol. Res. (1997) [Pubmed]
  6. Activation of the ERK/MAPK pathway by an isoform of rap1GAP associated with G alpha(i). Mochizuki, N., Ohba, Y., Kiyokawa, E., Kurata, T., Murakami, T., Ozaki, T., Kitabatake, A., Nagashima, K., Matsuda, M. Nature (1999) [Pubmed]
  7. Cyclic AMP induces integrin-mediated cell adhesion through Epac and Rap1 upon stimulation of the beta 2-adrenergic receptor. Rangarajan, S., Enserink, J.M., Kuiperij, H.B., de Rooij, J., Price, L.S., Schwede, F., Bos, J.L. J. Cell Biol. (2003) [Pubmed]
  8. Rap1GAP2 is a new GTPase-activating protein of Rap1 expressed in human platelets. Schultess, J., Danielewski, O., Smolenski, A.P. Blood (2005) [Pubmed]
  9. Functional interaction between Galpha(z) and Rap1GAP suggests a novel form of cellular cross-talk. Meng, J., Glick, J.L., Polakis, P., Casey, P.J. J. Biol. Chem. (1999) [Pubmed]
  10. The RAP1GA1 locus for human Rap1-GTPase activating protein 1 maps to chromosome 1p36.1-->p35. Weiss, J., Rubinfeld, B., Polakis, P.G., McCormick, F., Cavenee, W.K., Arden, K.C. Cytogenet. Cell Genet. (1994) [Pubmed]
  11. The GTPase-activating protein Rap1GAP uses a catalytic asparagine. Daumke, O., Weyand, M., Chakrabarti, P.P., Vetter, I.R., Wittinghofer, A. Nature (2004) [Pubmed]
  12. Phosphorylation of Rap1GAP during the cell cycle. Janoueix-Lerosey, I., Fontenay, M., Tobelem, G., Tavitian, A., Polakis, P., de Gunzburg, J. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  13. The small GTPase Rap1 is activated by turbulence and is involved in integrin [alpha]IIb[beta]3-mediated cell adhesion in human megakaryocytes. de Bruyn, K.M., Zwartkruis, F.J., de Rooij, J., Akkerman, J.W., Bos, J.L. J. Biol. Chem. (2003) [Pubmed]
  14. Guanine nucleotide binding properties of rap1 purified from human neutrophils. Bokoch, G.M., Quilliam, L.A. Biochem. J. (1990) [Pubmed]
  15. Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity. Wienecke, R., König, A., DeClue, J.E. J. Biol. Chem. (1995) [Pubmed]
  16. Rap1 GTPase inhibits leukocyte transmigration by promoting endothelial barrier function. Wittchen, E.S., Worthylake, R.A., Kelly, P., Casey, P.J., Quilliam, L.A., Burridge, K. J. Biol. Chem. (2005) [Pubmed]
  17. MAP kinase stimulation by cAMP does not require RAP1 but SRC family kinases. Klinger, M., Kudlacek, O., Seidel, M.G., Freissmuth, M., Sexl, V. J. Biol. Chem. (2002) [Pubmed]
  18. AF-6 controls integrin-mediated cell adhesion by regulating Rap1 activation through the specific recruitment of Rap1GTP and SPA-1. Su, L., Hattori, M., Moriyama, M., Murata, N., Harazaki, M., Kaibuchi, K., Minato, N. J. Biol. Chem. (2003) [Pubmed]
  19. Mitogen-inducible SIPA1 is mapped to the conserved syntenic groups of chromosome 19 in mouse and chromosome 11q13.3 centromeric to BCL1 in human. Wada, Y., Kubota, H., Maeda, M., Taniwaki, M., Hattori, M., Imamura, S., Iwai, K., Minato, N. Genomics (1997) [Pubmed]
  20. Adaptor protein Crk is required for ephrin-B1-induced membrane ruffling and focal complex assembly of human aortic endothelial cells. Nagashima, K., Endo, A., Ogita, H., Kawana, A., Yamagishi, A., Kitabatake, A., Matsuda, M., Mochizuki, N. Mol. Biol. Cell (2002) [Pubmed]
  21. CD28 and the tyrosine kinase lck stimulate mitogen-activated protein kinase activity in T cells via inhibition of the small G protein Rap1. Carey, K.D., Dillon, T.J., Schmitt, J.M., Baird, A.M., Holdorf, A.D., Straus, D.B., Shaw, A.S., Stork, P.J. Mol. Cell. Biol. (2000) [Pubmed]
  22. Purification, crystallization and preliminary structural characterization of human Rap1GAP. Daumke, O., Wittinghofer, A., Weyand, M. Acta Crystallogr. D Biol. Crystallogr. (2004) [Pubmed]
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