RAC1

Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)
	; PDB rendering based on 1ds6.
Available structures
PDB	1E96, 1FOE, 1G4U, 1HE1, 1HH4, 1I4D, 1I4L, 1I4T, 1MH1, 1RYF, 1RYH, 2FJU, 2H7V, 2NZ8, 2P2L, 2RMK, 2VRW, 2WKP, 2WKQ, 2WKR, 3BJI
Identifiers
Symbols	RAC1; MGC111543; TC-25; p21-Rac1
External IDs	OMIM: 602048 MGI: 97845 HomoloGene: 69035 GeneCards: RAC1 Gene
Gene Ontology
Molecular function	• nucleotide binding; • GTPase activity; • protein binding; • GTP binding; • enzyme binding; • GTP-dependent protein binding; • thioesterase binding;
Cellular component	• cytosol; • cytosol; • plasma membrane; • plasma membrane; • membrane; • melanosome;
Biological process	• GTP catabolic process; • apoptosis; • cellular component movement; • inflammatory response; • cell adhesion; • cell-matrix adhesion; • small GTPase mediated signal transduction; • axon guidance; • blood coagulation; • induction of apoptosis by extracellular signals; • response to wounding; • anatomical structure morphogenesis; • regulation of hydrogen peroxide metabolic process; • positive regulation of lamellipodium assembly; • viral reproduction; • lamellipodium assembly; • actin filament polymerization; • platelet activation; • regulation of cell migration; • T cell costimulation; • ruffle organization; • ruffle organization; • negative regulation of interleukin-23 production; • positive regulation of Rho protein signal transduction; • intracellular signal transduction; • nerve growth factor receptor signaling pathway; • negative regulation of receptor-mediated endocytosis; • cell motility; • regulation of defense response to virus by virus; • regulation of small GTPase mediated signal transduction; • localization within membrane; • regulation of respiratory burst;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs

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"Rac1" redirects here. For the first game in the Ratchet & Clank series, see Ratchet & Clank.

Ras-related C3 botulinum toxin substrate 1 also known as Rac1 is a protein that in humans is encoded by the RAC1 gene.^[1]^[2] Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.^[3]

[edit] Function

Rac1 is a small (~21 kDa) signaling G protein (more specifically a GTPase), and is a member of the Rac subfamily of the family Rho family of GTPases. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.^[4]

Rac1 is a pleiotropic regulator of many cellular processes, including the cell cycle, cell-cell adhesion, motility (through the actin network), and of epithelial differentiation (proposed to be necessary for maintaining epidermal stem cells).

[edit] Interactions

RAC1 has been shown to interact with ARFIP2,^[5]^[6]^[7] Myotonic dystrophy protein kinase,^[8] T-cell lymphoma invasion and metastasis-inducing protein 1,^[9]^[10] PARD6B,^[11] PAK1,^[12]^[13]^[14] PAK3,^[5] ARHGDIA,^[15]^[16]^[17]^[18]^[19]^[20] Myd88,^[21] PARD6A,^[22]^[11] STAT3,^[23] IQGAP2,^[24] NCKAP1,^[25] IQGAP1,^[26]^[27]^[28]^[14] FHOD1,^[29] BAIAP2,^[30] RICS^[31]^[32] and FMNL1.^[33]

[edit] References

^ Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R (October 1989). "rac, a novel ras-related family of proteins that are botulinum toxin substrates". J. Biol. Chem. 264 (28): 16378–82. PMID 2674130.
^ Jordan P, Brazåo R, Boavida MG, Gespach C, Chastre E (November 1999). "Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors". Oncogene 18 (48): 6835–9. doi:10.1038/sj.onc.1203233. PMID 10597294.
^ "Entrez Gene: RAC1 ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5879.
^ Ridley A. (2006). "Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking". Trends Cell Biol 16 (10): 522–9. doi:10.1016/j.tcb.2006.08.006. ISSN 0962-8924. PMID 16949823.
^ ^a ^b Shin, O H; Exton J H (Aug. 2001). "Differential binding of arfaptin 2/POR1 to ADP-ribosylation factors and Rac1". Biochem. Biophys. Res. Commun. (United States) 285 (5): 1267–73. doi:10.1006/bbrc.2001.5330. ISSN 0006-291X. PMID 11478794.
^ Van Aelst, L; Joneson T, Bar-Sagi D (Aug. 1996). "Identification of a novel Rac1-interacting protein involved in membrane ruffling". EMBO J. (ENGLAND) 15 (15): 3778–86. ISSN 0261-4189. PMC 452058. PMID 8670882. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=452058.
^ Tarricone, C; Xiao B, Justin N, Walker P A, Rittinger K, Gamblin S J, Smerdon S J (May. 2001). "The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways". Nature (England) 411 (6834): 215–9. doi:10.1038/35075620. ISSN 0028-0836. PMID 11346801.
^ Shimizu, M; Wang W, Walch E T, Dunne P W, Epstein H F (Jun. 2000). "Rac-1 and Raf-1 kinases, components of distinct signaling pathways, activate myotonic dystrophy protein kinase". FEBS Lett. (NETHERLANDS) 475 (3): 273–7. doi:10.1016/S0014-5793(00)01692-6. ISSN 0014-5793. PMID 10869570.
^ Worthylake, D K; Rossman K L, Sondek J (Dec. 2000). "Crystal structure of Rac1 in complex with the guanine nucleotide exchange region of Tiam1". Nature (England) 408 (6813): 682–8. doi:10.1038/35047014. ISSN 0028-0836. PMID 11130063.
^ Gao, Y; Xing J, Streuli M, Leto T L, Zheng Y (Dec. 2001). "Trp(56) of rac1 specifies interaction with a subset of guanine nucleotide exchange factors". J. Biol. Chem. (United States) 276 (50): 47530–41. doi:10.1074/jbc.M108865200. ISSN 0021-9258. PMID 11595749.
^ ^a ^b Noda, Y; Takeya R, Ohno S, Naito S, Ito T, Sumimoto H (Feb. 2001). "Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C". Genes Cells (England) 6 (2): 107–19. doi:10.1046/j.1365-2443.2001.00404.x. ISSN 1356-9597. PMID 11260256.
^ Katoh, Hironori; Negishi Manabu (Jul. 2003). "RhoG activates Rac1 by direct interaction with the Dock180-binding protein Elmo". Nature (England) 424 (6947): 461–4. doi:10.1038/nature01817. PMID 12879077.
^ Seoh, Mui Leng; Ng Chong Han, Yong Jeffery, Lim Louis, Leung Thomas (Mar. 2003). "ArhGAP15, a novel human RacGAP protein with GTPase binding property". FEBS Lett. (Netherlands) 539 (1–3): 131–7. doi:10.1016/S0014-5793(03)00213-8. ISSN 0014-5793. PMID 12650940.
^ ^a ^b Zhang, B; Chernoff J, Zheng Y (Apr. 1998). "Interaction of Rac1 with GTPase-activating proteins and putative effectors. A comparison with Cdc42 and RhoA". J. Biol. Chem. (UNITED STATES) 273 (15): 8776–82. doi:10.1074/jbc.273.15.8776. ISSN 0021-9258. PMID 9535855.
^ Ewing, Rob M; Chu Peter, Elisma Fred, Li Hongyan, Taylor Paul, Climie Shane, McBroom-Cerajewski Linda, Robinson Mark D, O'Connor Liam, Li Michael, Taylor Rod, Dharsee Moyez, Ho Yuen, Heilbut Adrian, Moore Lynda, Zhang Shudong, Ornatsky Olga, Bukhman Yury V, Ethier Martin, Sheng Yinglun, Vasilescu Julian, Abu-Farha Mohamed, Lambert Jean-Philippe, Duewel Henry S, Stewart Ian I, Kuehl Bonnie, Hogue Kelly, Colwill Karen, Gladwish Katharine, Muskat Brenda, Kinach Robert, Adams Sally-Lin, Moran Michael F, Morin Gregg B, Topaloglou Thodoros, Figeys Daniel (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. (England) 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1847948.
^ Grizot, S; Fauré J, Fieschi F, Vignais P V, Dagher M C, Pebay-Peyroula E (Aug. 2001). "Crystal structure of the Rac1-RhoGDI complex involved in nadph oxidase activation". Biochemistry (United States) 40 (34): 10007–13. doi:10.1021/bi010288k. ISSN 0006-2960. PMID 11513578.
^ Lian, L Y; Barsukov I, Golovanov A P, Hawkins D I, Badii R, Sze K H, Keep N H, Bokoch G M, Roberts G C (Jan. 2000). "Mapping the binding site for the GTP-binding protein Rac-1 on its inhibitor RhoGDI-1". Structure (ENGLAND) 8 (1): 47–55. doi:10.1016/S0969-2126(00)00080-0. ISSN 0969-2126. PMID 10673424.
^ Gorvel, J P; Chang T C, Boretto J, Azuma T, Chavrier P (Jan. 1998). "Differential properties of D4/LyGDI versus RhoGDI: phosphorylation and rho GTPase selectivity". FEBS Lett. (NETHERLANDS) 422 (2): 269–73. doi:10.1016/S0014-5793(98)00020-9. ISSN 0014-5793. PMID 9490022.
^ Di-Poï, N; Fauré J, Grizot S, Molnár G, Pick E, Dagher M C (Aug. 2001). "Mechanism of NADPH oxidase activation by the Rac/Rho-GDI complex". Biochemistry (United States) 40 (34): 10014–22. doi:10.1021/bi010289c. ISSN 0006-2960. PMID 11513579.
^ Fauré, J; Dagher M C (May. 2001). "Interactions between Rho GTPases and Rho GDP dissociation inhibitor (Rho-GDI)". Biochimie (France) 83 (5): 409–14. doi:10.1016/S0300-9084(01)01263-9. ISSN 0300-9084. PMID 11368848.
^ Jefferies, C; Bowie A, Brady G, Cooke E L, Li X, O'Neill L A (Jul. 2001). "Transactivation by the p65 Subunit of NF-κB in Response to Interleukin-1 (IL-1) Involves MyD88, IL-1 Receptor-Associated Kinase 1, TRAF-6, and Rac1". Mol. Cell. Biol. (United States) 21 (14): 4544–52. doi:10.1128/MCB.21.14.4544-4552.2001. ISSN 0270-7306. PMC 87113. PMID 11416133. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87113.
^ Qiu, R G; Abo A, Steven Martin G (Jun. 2000). "A human homolog of the C. elegans polarity determinant Par-6 links Rac and Cdc42 to PKCzeta signaling and cell transformation". Curr. Biol. (ENGLAND) 10 (12): 697–707. doi:10.1016/S0960-9822(00)00535-2. ISSN 0960-9822. PMID 10873802.
^ Simon, A R; Vikis H G, Stewart S, Fanburg B L, Cochran B H, Guan K L (Oct. 2000). "Regulation of STAT3 by direct binding to the Rac1 GTPase". Science (UNITED STATES) 290 (5489): 144–7. doi:10.1126/science.290.5489.144. ISSN 0036-8075. PMID 11021801.
^ Brill, S; Li S, Lyman C W, Church D M, Wasmuth J J, Weissbach L, Bernards A, Snijders A J (Sep. 1996). "The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases". Mol. Cell. Biol. (UNITED STATES) 16 (9): 4869–78. ISSN 0270-7306. PMC 231489. PMID 8756646. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231489.
^ Kitamura, Y; Kitamura T, Sakaue H, Maeda T, Ueno H, Nishio S, Ohno S, Osada S i, Sakaue M, Ogawa W, Kasuga M (Mar. 1997). "Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac". Biochem. J. (ENGLAND) 322 ( Pt 3) (Pt 3): 873–8. ISSN 0264-6021. PMC 1218269. PMID 9148763. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1218269.
^ Kuroda, S; Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K (Sep. 1996). "Identification of IQGAP as a putative target for the small GTPases, Cdc42 and Rac1". J. Biol. Chem. (UNITED STATES) 271 (38): 23363–7. doi:10.1074/jbc.271.38.23363. ISSN 0021-9258. PMID 8798539.
^ Fukata, Masaki; Watanabe Takashi, Noritake Jun, Nakagawa Masato, Yamaga Masaki, Kuroda Shinya, Matsuura Yoshiharu, Iwamatsu Akihiro, Perez Franck, Kaibuchi Kozo (Jun. 2002). "Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170". Cell (United States) 109 (7): 873–85. doi:10.1016/S0092-8674(02)00800-0. ISSN 0092-8674. PMID 12110184.
^ Hart, M J; Callow M G, Souza B, Polakis P (Jun. 1996). "IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs". EMBO J. (ENGLAND) 15 (12): 2997–3005. ISSN 0261-4189. PMC 450241. PMID 8670801. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=450241.
^ Westendorf, J J (Dec. 2001). "The formin/diaphanous-related protein, FHOS, interacts with Rac1 and activates transcription from the serum response element". J. Biol. Chem. (United States) 276 (49): 46453–9. doi:10.1074/jbc.M105162200. ISSN 0021-9258. PMID 11590143.
^ Miki, H; Yamaguchi H, Suetsugu S, Takenawa T (Dec. 2000). "IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling". Nature (England) 408 (6813): 732–5. doi:10.1038/35047107. ISSN 0028-0836. PMID 11130076.
^ Zhao, Chunmei; Ma Hong, Bossy-Wetzel Ella, Lipton Stuart A, Zhang Zhuohua, Feng Gen-Sheng (Sep. 2003). "GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2". J. Biol. Chem. (United States) 278 (36): 34641–53. doi:10.1074/jbc.M304594200. ISSN 0021-9258. PMID 12819203.
^ Moon, Sun Young; Zang Heesuk, Zheng Yi (Feb. 2003). "Characterization of a brain-specific Rho GTPase-activating protein, p200RhoGAP". J. Biol. Chem. (United States) 278 (6): 4151–9. doi:10.1074/jbc.M207789200. ISSN 0021-9258. PMID 12454018.
^ Yayoshi-Yamamoto, S; Taniuchi I, Watanabe T (Sep. 2000). "FRL, a Novel Formin-Related Protein, Binds to Rac and Regulates Cell Motility and Survival of Macrophages". Mol. Cell. Biol. (UNITED STATES) 20 (18): 6872–81. doi:10.1128/MCB.20.18.6872-6881.2000. ISSN 0270-7306. PMC 86228. PMID 10958683. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=86228.

[edit] Further reading

Benitah SA, Frye M, Glogauer M, Watt FM (2005). "Stem cell depletion through epidermal deletion of Rac1". Science 309 (5736): 933–5. doi:10.1126/science.1113579. PMID 16081735.
Dorseuil O, Gacon G (1997). "[Signal transduction by Rac small G proteins in phagocytes] [Signal transduction by Rac small G proteins in phagocytes]" (in French). C. R. Seances Soc. Biol. Fil. 191 (2): 237–46. PMID 9255350.
Ramakers GJ (2002). "Rho proteins, mental retardation and the cellular basis of cognition". Trends Neurosci. 25 (4): 191–9. doi:10.1016/S0166-2236(00)02118-4. PMID 11998687.
Esufali S, Charames S, Bapat B (2007). "Suppression of Wnt signalling leads to stabilization of Rac1 isoforms". FEBS letters. 581 (25): 4850–4856. doi:10.1016/j.febslet.2007.09.013. PMID 17888911.