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Gene Review

Racgap1  -  Rac GTPase-activating protein 1

Mus musculus

Synonyms: AI227039, AI327394, Band25, GTPase, Male germ cell RacGap, ...
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Disease relevance of Racgap1


High impact information on Racgap1

  • Here we show that Tagap1, a GTPase-activating protein, can act as a distorter [6].
  • Loner localizes to subcellular sites of fusion and acts downstream of cell surface fusion receptors by recruiting the small GTPase ARF6 and stimulating guanine nucleotide exchange [7].
  • Loner and ARF6, which also control the proper membrane localization of another small GTPase, Rac, are key components of a cellular apparatus required for myoblast fusion and muscle development [7].
  • DOCK4 specifically activates Rap GTPase, enhancing the formation of adherens junctions [8].
  • Thus, tyrosine phosphorylation relieves autoinhibition by exposing the GTPase interaction surface of the DH domain, which is obligatory for Vav activation [9].

Chemical compound and disease context of Racgap1

  • Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft-associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation [10].
  • This inhibitory effect was attenuated by inactivation of small GTPase Rho with C3 exotoxin but not by inactivation of G(i) with pertussis toxin [11].
  • By using phospholipid vesicles reconstituted with human wild type or mutant M6P/IGF II receptors and pertussis toxin-sensitive G-proteins, no stimulation of GTP gamma S binding to or GTPase activity of G(i)2, G(o)1, or G(i)/G(o) mixtures were observed in response to 1 microM IGF II [12].
  • Such F-actin coating occurred exclusively at the surface of granules undergoing exocytosis and was prevented either by latrunculin-A, which inhibits actin polymerization, or by Clostridium botulinum exoenzyme C3, which inhibits the small GTPase Rho [13].
  • Mouse neuroblastoma x rat glioma hybrid cells (NG108-15) express an opioid receptor of the delta subclass which both stimulates high-affinity GTPase activity and inhibits adenylate cyclase by interacting with a pertussis-toxin-sensitive guanine-nucleotide-binding protein(s) (G-protein) [14].

Biological context of Racgap1


Anatomical context of Racgap1


Associations of Racgap1 with chemical compounds

  • Analyses using a GAP-inactive mutant and 2 deletion mutants of MgcRacGAP indicated that the GAP activity was dispensable, but the myosin-like domain and the cysteine-rich domain were indispensable for growth suppression and macrophage differentiation [22].
  • To further investigate the signal mechanisms that regulate the cellular effects of 8-Cl-cAMP, we focused on a small GTPase Rap1 that is known to be involved in growth inhibition and reverse-transformation [23].
  • Interestingly, MgcRacGAP in the midbody was phosphorylated probably on serine and threonine residues [17].
  • These results indicate that MgcRacGAP regulates cytokinesis and cellular differentiation as a regulator of Rho family of GTPase and suggest that this process is controlled by some serine/threonine kinases [17].
  • We transfected Madin-Darby canine kidney cells with rab4, the GTPase-deficient mutant rab4Q67L, and the dominant negative mutant rab4S22N that poorly binds guanine nucleotides [24].

Physical interactions of Racgap1

  • One established function of the Eps8-Abi1 complex is to participate in the activation of the small GTPase Rac, suggesting a multifaceted role for this complex in actin dynamics, possibly through the participation in alternative larger complexes [25].
  • Crystal structure of the DH/PH fragment of Dbs without bound GTPase [26].
  • Structure of the p115RhoGEF rgRGS domain-Galpha13/i1 chimera complex suggests convergent evolution of a GTPase activator [27].
  • At excitatory synapses, the postsynaptic scaffolding protein postsynaptic density 95 (PSD-95) couples NMDA receptors (NMDARs) to the Ras GTPase-activating protein SynGAP [28].
  • Furthermore, Fab fragments of a monoclonal antibody known to neutralize antiviral activity block GTPase activity by binding an epitope in the carboxy-terminal half of Mx2 or Mx3 protein [29].

Enzymatic interactions of Racgap1


Regulatory relationships of Racgap1

  • The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins [32].
  • The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin [33].
  • This arginine residue functions effectively as an "arginine finger" in the GTPase activating reaction to confer the catalytic GAP activity but is not essential for the homophilic binding interactions of Rho family proteins [34].
  • Inhibition of actin polymerization using latrunculin A reduced the ability of constitutively active GTPase mutants to stimulate apoptosis and blocked Fas-induced activation of caspase-3 [35].
  • The NF1 tumor suppressor gene encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras signaling [36].

Other interactions of Racgap1


Analytical, diagnostic and therapeutic context of Racgap1


  1. Stromal cell-derived factor-1-induced LFA-1 activation during in vivo migration of T cell hybridoma cells requires Gq/11, RhoA, and myosin, as well as Gi and Cdc42. Soede, R.D., Zeelenberg, I.S., Wijnands, Y.M., Kamp, M., Roos, E. J. Immunol. (2001) [Pubmed]
  2. In vivo modifications of small GTPase Rac and Cdc42 by Bordetella dermonecrotic toxin. Masuda, M., Minami, M., Shime, H., Matsuzawa, T., Horiguchi, Y. Infect. Immun. (2002) [Pubmed]
  3. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Hadano, S., Hand, C.K., Osuga, H., Yanagisawa, Y., Otomo, A., Devon, R.S., Miyamoto, N., Showguchi-Miyata, J., Okada, Y., Singaraja, R., Figlewicz, D.A., Kwiatkowski, T., Hosler, B.A., Sagie, T., Skaug, J., Nasir, J., Brown, R.H., Scherer, S.W., Rouleau, G.A., Hayden, M.R., Ikeda, J.E. Nat. Genet. (2001) [Pubmed]
  4. Genomic analysis of metastasis reveals an essential role for RhoC. Clark, E.A., Golub, T.R., Lander, E.S., Hynes, R.O. Nature (2000) [Pubmed]
  5. Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting. Weinstein, L.S., Yu, S., Warner, D.R., Liu, J. Endocr. Rev. (2001) [Pubmed]
  6. The t complex-encoded GTPase-activating protein Tagap1 acts as a transmission ratio distorter in mice. Bauer, H., Willert, J., Koschorz, B., Herrmann, B.G. Nat. Genet. (2005) [Pubmed]
  7. Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Chen, E.H., Pryce, B.A., Tzeng, J.A., Gonzalez, G.A., Olson, E.N. Cell (2003) [Pubmed]
  8. DOCK4, a GTPase activator, is disrupted during tumorigenesis. Yajnik, V., Paulding, C., Sordella, R., McClatchey, A.I., Saito, M., Wahrer, D.C., Reynolds, P., Bell, D.W., Lake, R., van den Heuvel, S., Settleman, J., Haber, D.A. Cell (2003) [Pubmed]
  9. Structural basis for relief of autoinhibition of the Dbl homology domain of proto-oncogene Vav by tyrosine phosphorylation. Aghazadeh, B., Lowry, W.E., Huang, X.Y., Rosen, M.K. Cell (2000) [Pubmed]
  10. Statins inhibit HIV-1 infection by down-regulating Rho activity. del Real, G., Jiménez-Baranda, S., Mira, E., Lacalle, R.A., Lucas, P., Gómez-Moutón, C., Alegret, M., Peña, J.M., Rodríguez-Zapata, M., Alvarez-Mon, M., Martínez-A, C., Mañes, S. J. Exp. Med. (2004) [Pubmed]
  11. Antiproliferative property of sphingosine 1-phosphate in rat hepatocytes involves activation of Rho via Edg-5. Ikeda, H., Satoh, H., Yanase, M., Inoue, Y., Tomiya, T., Arai, M., Tejima, K., Nagashima, K., Maekawa, H., Yahagi, N., Yatomi, Y., Sakurada, S., Takuwa, Y., Ogata, I., Kimura, S., Fujiwara, K. Gastroenterology (2003) [Pubmed]
  12. Mannose 6-phosphate/insulin-like growth factor II receptor fails to interact with G-proteins. Analysis of mutant cytoplasmic receptor domains. Körner, C., Nürnberg, B., Uhde, M., Braulke, T. J. Biol. Chem. (1995) [Pubmed]
  13. Stabilization of exocytosis by dynamic F-actin coating of zymogen granules in pancreatic acini. Nemoto, T., Kojima, T., Oshima, A., Bito, H., Kasai, H. J. Biol. Chem. (2004) [Pubmed]
  14. Delta-opioid-receptor-mediated inhibition of adenylate cyclase is transduced specifically by the guanine-nucleotide-binding protein Gi2. McKenzie, F.R., Milligan, G. Biochem. J. (1990) [Pubmed]
  15. Open brain gene product Rab23: Expression pattern in the adult mouse brain and functional characterization. Guo, A., Wang, T., Ng, E.L., Aulia, S., Chong, K.H., Teng, F.Y., Wang, Y., Tang, B.L. J. Neurosci. Res. (2006) [Pubmed]
  16. Cdc42 is implicated in polarity during meiotic resumption and blastocyst formation in the mouse. Cui, X.S., Li, X.Y., Kim, N.H. Mol. Reprod. Dev. (2007) [Pubmed]
  17. Role of MgcRacGAP/Cyk4 as a regulator of the small GTPase Rho family in cytokinesis and cell differentiation. Kitamura, T., Kawashima, T., Minoshima, Y., Tonozuka, Y., Hirose, K., Nosaka, T. Cell Struct. Funct. (2001) [Pubmed]
  18. Identification and characterization of a transcript for a novel Rac GTPase-activating protein in terminally differentiating 3T3-L1 adipocytes. Wooltorton, E.J., Haliotis, T., Mueller, C.R. DNA Cell Biol. (1999) [Pubmed]
  19. Induction of filopodium formation by a WASP-related actin-depolymerizing protein N-WASP. Miki, H., Sasaki, T., Takai, Y., Takenawa, T. Nature (1998) [Pubmed]
  20. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin. Wu, X., Quondamatteo, F., Lefever, T., Czuchra, A., Meyer, H., Chrostek, A., Paus, R., Langbein, L., Brakebusch, C. Genes Dev. (2006) [Pubmed]
  21. The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Schwamborn, J.C., Püschel, A.W. Nat. Neurosci. (2004) [Pubmed]
  22. MgcRacGAP is involved in the control of growth and differentiation of hematopoietic cells. Kawashima, T., Hirose, K., Satoh, T., Kaneko, A., Ikeda, Y., Kaziro, Y., Nosaka, T., Kitamura, T. Blood (2000) [Pubmed]
  23. Rap1 and p38 MAPK mediate 8-chloro-cAMP-induced growth inhibition in mouse fibroblast DT cells. Ahn, Y.H., Han, J.H., Hong, S.H. J. Cell. Physiol. (2006) [Pubmed]
  24. rab4 regulates transport to the apical plasma membrane in Madin-Darby canine kidney cells. Mohrmann, K., Leijendekker, R., Gerez, L., van Der Sluijs, P. J. Biol. Chem. (2002) [Pubmed]
  25. Eps8 controls actin-based motility by capping the barbed ends of actin filaments. Disanza, A., Carlier, M.F., Stradal, T.E., Didry, D., Frittoli, E., Confalonieri, S., Croce, A., Wehland, J., Di Fiore, P.P., Scita, G. Nat. Cell Biol. (2004) [Pubmed]
  26. Crystal structure of the DH/PH fragment of Dbs without bound GTPase. Worthylake, D.K., Rossman, K.L., Sondek, J. Structure (Camb.) (2004) [Pubmed]
  27. Structure of the p115RhoGEF rgRGS domain-Galpha13/i1 chimera complex suggests convergent evolution of a GTPase activator. Chen, Z., Singer, W.D., Sternweis, P.C., Sprang, S.R. Nat. Struct. Mol. Biol. (2005) [Pubmed]
  28. SynGAP regulates ERK/MAPK signaling, synaptic plasticity, and learning in the complex with postsynaptic density 95 and NMDA receptor. Komiyama, N.H., Watabe, A.M., Carlisle, H.J., Porter, K., Charlesworth, P., Monti, J., Strathdee, D.J., O'Carroll, C.M., Martin, S.J., Morris, R.G., O'Dell, T.J., Grant, S.G. J. Neurosci. (2002) [Pubmed]
  29. Antiviral determinants of rat Mx GTPases map to the carboxy-terminal half. Johannes, L., Kambadur, R., Lee-Hellmich, H., Hodgkinson, C.A., Arnheiter, H., Meier, E. J. Virol. (1997) [Pubmed]
  30. Developmental regulation of tissue transglutaminase in the mouse forebrain. Bailey, C.D., Johnson, G.V. J. Neurochem. (2004) [Pubmed]
  31. RhoE function is regulated by ROCK I-mediated phosphorylation. Riento, K., Totty, N., Villalonga, P., Garg, R., Guasch, R., Ridley, A.J. EMBO J. (2005) [Pubmed]
  32. The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins. Chamberlain, M.D., Berry, T.R., Pastor, M.C., Anderson, D.H. J. Biol. Chem. (2004) [Pubmed]
  33. The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin. Jenna, S., Hussain, N.K., Danek, E.I., Triki, I., Wasiak, S., McPherson, P.S., Lamarche-Vane, N. J. Biol. Chem. (2002) [Pubmed]
  34. A built-in arginine finger triggers the self-stimulatory GTPase-activating activity of rho family GTPases. Zhang, B., Zhang, Y., Collins, C.C., Johnson, D.I., Zheng, Y. J. Biol. Chem. (1999) [Pubmed]
  35. Rho family proteins modulate rapid apoptosis induced by cytotoxic T lymphocytes and Fas. Subauste, M.C., Von Herrath, M., Benard, V., Chamberlain, C.E., Chuang, T.H., Chu, K., Bokoch, G.M., Hahn, K.M. J. Biol. Chem. (2000) [Pubmed]
  36. Neurofibromin-deficient Schwann cells secrete a potent migratory stimulus for Nf1+/- mast cells. Yang, F.C., Ingram, D.A., Chen, S., Hingtgen, C.M., Ratner, N., Monk, K.R., Clegg, T., White, H., Mead, L., Wenning, M.J., Williams, D.A., Kapur, R., Atkinson, S.J., Clapp, D.W. J. Clin. Invest. (2003) [Pubmed]
  37. WIP regulates N-WASP-mediated actin polymerization and filopodium formation. Martinez-Quiles, N., Rohatgi, R., Antón, I.M., Medina, M., Saville, S.P., Miki, H., Yamaguchi, H., Takenawa, T., Hartwig, J.H., Geha, R.S., Ramesh, N. Nat. Cell Biol. (2001) [Pubmed]
  38. A role for Pak protein kinases in Schwann cell transformation. Tang, Y., Marwaha, S., Rutkowski, J.L., Tennekoon, G.I., Phillips, P.C., Field, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  39. Fibrillar beta-amyloid-stimulated intracellular signaling cascades require Vav for induction of respiratory burst and phagocytosis in monocytes and microglia. Wilkinson, B., Koenigsknecht-Talboo, J., Grommes, C., Lee, C.Y., Landreth, G. J. Biol. Chem. (2006) [Pubmed]
  40. Requirement for C-terminal sequences in regulation of Ect2 guanine nucleotide exchange specificity and transformation. Solski, P.A., Wilder, R.S., Rossman, K.L., Sondek, J., Cox, A.D., Campbell, S.L., Der, C.J. J. Biol. Chem. (2004) [Pubmed]
  41. Regulation of innate immunity by Rho GTPases. Bokoch, G.M. Trends Cell Biol. (2005) [Pubmed]
  42. Role of the monomeric GTPase Rho in hematopoietic progenitor cell migration and transplantation. Göttig, S., Möbest, D., Rüster, B., Grace, B., Winter, S., Seifried, E., Gille, J., Wieland, T., Henschler, R. Eur. J. Immunol. (2006) [Pubmed]
  43. Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells. Naud, N., Touré, A., Liu, J., Pineau, C., Morin, L., Dorseuil, O., Escalier, D., Chardin, P., Gacon, G. Biochem. J. (2003) [Pubmed]
  44. MgcRacGAP, a new human GTPase-activating protein for Rac and Cdc42 similar to Drosophila rotundRacGAP gene product, is expressed in male germ cells. Touré, A., Dorseuil, O., Morin, L., Timmons, P., Jégou, B., Reibel, L., Gacon, G. J. Biol. Chem. (1998) [Pubmed]
  45. rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. Ridley, A.J., Self, A.J., Kasmi, F., Paterson, H.F., Hall, A., Marshall, C.J., Ellis, C. EMBO J. (1993) [Pubmed]
  46. High RhoA activity maintains the undifferentiated mesenchymal cell phenotype, whereas RhoA down-regulation by laminin-2 induces smooth muscle myogenesis. Beqaj, S., Jakkaraju, S., Mattingly, R.R., Pan, D., Schuger, L. J. Cell Biol. (2002) [Pubmed]
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