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Gene Review

RAC2  -  ras-related C3 botulinum toxin substrate 2...

Homo sapiens

Synonyms: EN-7, GX, Gx, HSPC022, Ras-related C3 botulinum toxin substrate 2, ...
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Disease relevance of RAC2


Psychiatry related information on RAC2


High impact information on RAC2


Chemical compound and disease context of RAC2


Biological context of RAC2


Anatomical context of RAC2

  • RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse [22].
  • Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1 [23].
  • We report here that the stimulation of the low-affinity receptor for immunoglobulin G (IgG) (FcgammaRIIIA, CD16) on primary human natural killer (NK) cells induces a phosphatidylinositol 3-kinase (PI3K)-dependent activation of the small G protein Arf6 [24].
  • We used a cell-free translocation system as well as intact normal and CGD neutrophils to determine whether the translocation of Rac2 is dependent upon the presence of the other oxidase components [3].
  • Rac2 protein expression was absent in infected HL-60 cells [1].

Associations of RAC2 with chemical compounds


Physical interactions of RAC2

  • Finally, we observe that p67phox interacts 6-fold better with Rac2 than with Rac1 [27].
  • The Rac target NADPH oxidase p67phox interacts preferentially with Rac2 rather than Rac1 [27].
  • Native prenylated small G proteins are either in the form of a complex in which the GDP bound G protein is associated with a guanine nucleotide dissociation inhibitor, GDI, or in an active GTP bound form able to trigger the activity of its effector [28].
  • We have solved the crystal structure of a complex between the RhoGDI homolog LyGDI and GDP-bound Rac2, which are abundant in leukocytes, representing the cytosolic, resting pool of Rho species to be activated by extracellular signals [29].
  • Both these p120Ras-GAP-binding proteins are of interest in connection with the regulation of the respiratory burst oxidase, Rap1A/Krev1 because it copurifies with cytochrome b558 and p190Ras-GAP because it inhibits the Rac2-dependent activation of the respiratory burst oxidase in a cell-free system [30].

Regulatory relationships of RAC2


Other interactions of RAC2


Analytical, diagnostic and therapeutic context of RAC2

  • The dissociation constant (K(d)) for interaction between actin and p47(phox) was estimated to be 0.45 microM by surface plasmon resonance, and that between actin and rac1 or rac2 was 1.7 or 4.6 microM, respectively [37].
  • In the present studies, oligonucleotide-directed mutagenesis was used to introduce a series of mutations into human rap1a or rac2 in the mammalian expression vector pSR alpha neo [38].
  • Full-length posttranslationally modified Rac2 was active, whereas only the 1-166 truncated form of Rap1a was functional in the cell-free system, and thus, clarification of the function of Rap1a and Rac2 in intact human phagocytes is needed to provide further insight into their roles as signal transducers from plasma membrane receptors [38].
  • Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein [39].
  • Gel permeation chromatography of radiolabeled hydrocarbons released from the rac1, rac2, and ralA proteins by reaction with Raney nickel catalyst indicated that unlike p21Hras, which was modified by a 15-carbon moiety, the rac and ralA translation products were modified by 20-carbon isoprenyl groups [40].


  1. Repression of rac2 mRNA expression by Anaplasma phagocytophila is essential to the inhibition of superoxide production and bacterial proliferation. Carlyon, J.A., Chan, W.T., Galán, J., Roos, D., Fikrig, E. J. Immunol. (2002) [Pubmed]
  2. Inhibition of superoxide production in B lymphocytes by rac antisense oligonucleotides. Dorseuil, O., Vazquez, A., Lang, P., Bertoglio, J., Gacon, G., Leca, G. J. Biol. Chem. (1992) [Pubmed]
  3. Rac translocates independently of the neutrophil NADPH oxidase components p47phox and p67phox. Evidence for its interaction with flavocytochrome b558. Heyworth, P.G., Bohl, B.P., Bokoch, G.M., Curnutte, J.T. J. Biol. Chem. (1994) [Pubmed]
  4. Small guanine nucleotide-binding proteins and myocardial hypertrophy. Clerk, A., Sugden, P.H. Circ. Res. (2000) [Pubmed]
  5. Rac2 expression and mutation in human brain tumors. Hwang, S.L., Lieu, A.S., Chang, J.H., Cheng, T.S., Cheng, C.Y., Lee, K.S., Lin, C.L., Howng, S.L., Hong, Y.R. Acta neurochirurgica. (2005) [Pubmed]
  6. Induction of p21ras in Alzheimer pathology. Gärtner, U., Holzer, M., Heumann, R., Arendt, T. Neuroreport (1995) [Pubmed]
  7. Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. Singer, W.D., Brown, H.A., Sternweis, P.C. Annu. Rev. Biochem. (1997) [Pubmed]
  8. ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates phospholipase D activity. Brown, H.A., Gutowski, S., Moomaw, C.R., Slaughter, C., Sternweis, P.C. Cell (1993) [Pubmed]
  9. Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. Mott, H.R., Owen, D., Nietlispach, D., Lowe, P.N., Manser, E., Lim, L., Laue, E.D. Nature (1999) [Pubmed]
  10. Rhodopsin-family receptors associate with small G proteins to activate phospholipase D. Mitchell, R., McCulloch, D., Lutz, E., Johnson, M., MacKenzie, C., Fennell, M., Fink, G., Zhou, W., Sealfon, S.C. Nature (1998) [Pubmed]
  11. Structure of the Sec7 domain of the Arf exchange factor ARNO. Cherfils, J., Ménétrey, J., Mathieu, M., Le Bras, G., Robineau, S., Béraud-Dufour, S., Antonny, B., Chardin, P. Nature (1998) [Pubmed]
  12. YRKL sequence of influenza virus M1 functions as the L domain motif and interacts with VPS28 and Cdc42. Hui, E.K., Barman, S., Tang, D.H., France, B., Nayak, D.P. J. Virol. (2006) [Pubmed]
  13. Rho regulates the hepatocyte growth factor/scatter factor-stimulated cell motility of human oral squamous cell carcinoma cells. Kitajo, H., Shibata, T., Nagayasu, H., Kawano, T., Hamada, J., Yamashita, T., Arisue, M. Oncol. Rep. (2003) [Pubmed]
  14. Delivery of proteins into living cells by reversible membrane permeabilization with streptolysin-O. Walev, I., Bhakdi, S.C., Hofmann, F., Djonder, N., Valeva, A., Aktories, K., Bhakdi, S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. Phosphoinositide 3-kinase-dependent and -independent activation of the small GTPase Rac2 in human neutrophils. Akasaki, T., Koga, H., Sumimoto, H. J. Biol. Chem. (1999) [Pubmed]
  16. Decreased expression of a member of the Rho GTPase family, Cdc42Hs, in cells from Tangier disease - the small G protein may play a role in cholesterol efflux. Hirano, K., Matsuura, F., Tsukamoto, K., Zhang, Z., Matsuyama, A., Takaishi, K., Komuro, R., Suehiro, T., Yamashita, S., Takai, Y., Matsuzawa, Y. FEBS Lett. (2000) [Pubmed]
  17. Small GTPase Rac1: structure, localization, and expression of the human gene. Matos, P., Skaug, J., Marques, B., Beck, S., Veríssimo, F., Gespach, C., Boavida, M.G., Scherer, S.W., Jordan, P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  18. Characterization of RAC3, a novel member of the Rho family. Haataja, L., Groffen, J., Heisterkamp, N. J. Biol. Chem. (1997) [Pubmed]
  19. Cytosolic guanine nucleotide-binding protein Rac2 operates in vivo as a component of the neutrophil respiratory burst oxidase. Transfer of Rac2 and the cytosolic oxidase components p47phox and p67phox to the submembranous actin cytoskeleton during oxidase activation. el Benna, J., Ruedi, J.M., Babior, B.M. J. Biol. Chem. (1994) [Pubmed]
  20. Regulation of the superoxide-generating NADPH oxidase by a small GTP-binding protein and its stimulatory and inhibitory GDP/GTP exchange proteins. Mizuno, T., Kaibuchi, K., Ando, S., Musha, T., Hiraoka, K., Takaishi, K., Asada, M., Nunoi, H., Matsuda, I., Takai, Y. J. Biol. Chem. (1992) [Pubmed]
  21. Down-regulation of Rac activity during beta 2 integrin-mediated adhesion of human neutrophils. Dib, K., Melander, F., Axelsson, L., Dagher, M.C., Aspenström, P., Andersson, T. J. Biol. Chem. (2003) [Pubmed]
  22. RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse. Gu, Y., Williams, D.A. J. Pediatr. Hematol. Oncol. (2002) [Pubmed]
  23. Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1. Clerk, A., Pham, F.H., Fuller, S.J., Sahai, E., Aktories, K., Marais, R., Marshall, C., Sugden, P.H. Mol. Cell. Biol. (2001) [Pubmed]
  24. Arf6: a new player in FcgammaRIIIA lymphocyte-mediated cytotoxicity. Galandrini, R., Micucci, F., Tassi, I., Cifone, M.G., Cinque, B., Piccoli, M., Frati, L., Santoni, A. Blood (2005) [Pubmed]
  25. Regulation of the human neutrophil NADPH oxidase by rho-related G-proteins. Kwong, C.H., Malech, H.L., Rotrosen, D., Leto, T.L. Biochemistry (1993) [Pubmed]
  26. Supervised membrane swimming: small G-protein lifeguards regulate PIPK signalling and monitor intracellular PtdIns(4,5)P2 pools. Santarius, M., Lee, C.H., Anderson, R.A. Biochem. J. (2006) [Pubmed]
  27. The Rac target NADPH oxidase p67phox interacts preferentially with Rac2 rather than Rac1. Dorseuil, O., Reibel, L., Bokoch, G.M., Camonis, J., Gacon, G. J. Biol. Chem. (1996) [Pubmed]
  28. Small G proteins and the neutrophil NADPH oxidase. Dagher, M.C., Fuchs, A., Bourmeyster, N., Jouan, A., Vignais, P.V. Biochimie (1995) [Pubmed]
  29. The Rac-RhoGDI complex and the structural basis for the regulation of Rho proteins by RhoGDI. Scheffzek, K., Stephan, I., Jensen, O.N., Illenberger, D., Gierschik, P. Nat. Struct. Biol. (2000) [Pubmed]
  30. Enhancement of protein kinase C-dependent O2 production in Epstein-Barr virus-transformed B lymphocytes by p120Ras-GAP antisense oligonucleotide. Schmid, E., Koziol, J.A., Babior, B.M. J. Biol. Chem. (1996) [Pubmed]
  31. Comparative functional analysis of the Rac GTPases. Haeusler, L.C., Blumenstein, L., Stege, P., Dvorsky, R., Ahmadian, M.R. FEBS Lett. (2003) [Pubmed]
  32. The mechanism of p21-activated kinase 2 autoactivation. Wu, H., Wang, Z.X. J. Biol. Chem. (2003) [Pubmed]
  33. The insulin receptor substrate IRSp53 links postsynaptic shank1 to the small G-protein cdc42. Soltau, M., Richter, D., Kreienkamp, H.J. Mol. Cell. Neurosci. (2002) [Pubmed]
  34. Regulation of phospholipase D by low molecular weight GTP-binding proteins. Kanaho, Y., Yokozeki, T., Kuribara, H. Journal of lipid mediators and cell signalling. (1996) [Pubmed]
  35. Structure and chromosomal assignment to 22q12 and 17qter of the ras-related Rac2 and Rac3 human genes. Courjal, F., Chuchana, P., Theillet, C., Fort, P. Genomics (1997) [Pubmed]
  36. DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription. Nishihara, H., Maeda, M., Tsuda, M., Makino, Y., Sawa, H., Nagashima, K., Tanaka, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  37. Direct interaction of actin with p47(phox) of neutrophil NADPH oxidase. Tamura, M., Kai, T., Tsunawaki, S., Lambeth, J.D., Kameda, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  38. Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation. Gabig, T.G., Crean, C.D., Mantel, P.L., Rosli, R. Blood (1995) [Pubmed]
  39. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Ambruso, D.R., Knall, C., Abell, A.N., Panepinto, J., Kurkchubasche, A., Thurman, G., Gonzalez-Aller, C., Hiester, A., deBoer, M., Harbeck, R.J., Oyer, R., Johnson, G.L., Roos, D. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  40. Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA. Kinsella, B.T., Erdman, R.A., Maltese, W.A. J. Biol. Chem. (1991) [Pubmed]
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