Rac1 (RAS-related C3 botulinus toxin substrate 1) は、ヒト細胞に存在するタンパク質であり、RAC1遺伝子によりコードされている[5][6]。RAC1は選択的スプライシングにより異なる機能を持ったいくつかのタンパク質を生成しており、このうちの1つがRac1である[7]。
概要 PDBに登録されている構造, PDB ...
RAC1 |
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PDBに登録されている構造 |
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PDB | オルソログ検索: RCSB PDBe PDBj |
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PDBのIDコード一覧 |
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1E96, 1FOE, 1G4U, 1HE1, 1HH4, 1I4D, 1I4L, 1I4T, 1MH1, 1RYF, 1RYH, 2FJU, 2H7V, 2NZ8, 2P2L, 2RMK, 2VRW, 2WKP, 2WKQ, 2WKR, 2YIN, 3B13, 3BJI, 3RYT, 3SBD, 3SBE, 3SU8, 3SUA, 3TH5, 4GZL, 4GZM, 4YON, 5FI0 |
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識別子 |
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記号 | RAC1, MIG5, Rac-1, TC-25, p21-Rac1, ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), Rac family small GTPase 1, MRD48 |
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外部ID | OMIM: 602048 MGI: 97845 HomoloGene: 69035 GeneCards: RAC1 |
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オルソログ |
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種 | ヒト | マウス |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | | |
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RefSeq (タンパク質) | | |
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場所 (UCSC) | Chr 7: 6.37 – 6.4 Mb | Chr 7: 143.49 – 143.51 Mb |
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PubMed検索 | [3] | [4] |
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ウィキデータ |
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閉じる
Rac1は、悪性黒色腫[8][9][10]や肺非小細胞癌[11]
を含むさまざまな癌の発生において、重要な役割を果たしていると考えられている。そのため、現在これらの疾患に対する治療標的と考えられている[12]。
低分子量GTPアーゼの1つであるうえ、RhoファミリーGタンパク質であるRacサブファミリーのメンバーでもある。このスーパーファミリーのメンバーは、細胞の増殖や細胞骨格の再構築、プロテインキナーゼの活性化などさまざまな細胞における事象を制御している[13]。
Rac1は、細胞周期や細胞接着、(アクチンネットワークを介した)細胞運動、上皮細胞における悪性形質転換(上皮幹細胞維持における必要物質であると考えられている)などを含む多くの細胞プロセスにおける、多方面的な制御因子である。
ARFIP2[14][15][16]、Myotonic dystrophy protein kinase[17]、T-cell lymphoma invasion and metastasis-inducing protein 1[18][19]、PARD6B[20]、PAK1[21][22][23]、PAK3[14]、ARHGDIA[24][25][26][27][28][29]、Myd88[30]、PARD6A,[20][31]、STAT3[32]、IQGAP2[33]、NCKAP1[34]、IQGAP1[23][35][36][37]、FHOD1[38]、BAIAP2[39]、RICS[40][41]、FMNL1[42]などのタンパク質と相互作用することが明らかにされている。
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. Zhou, C; Licciulli, S; Avila, J L; Cho, M; Troutman, S; Jiang, P; Kossenkov, A V; Showe, L C et al. (2012). “The Rac1 splice form Rac1b promotes K-ras-induced lung tumorigenesis”. Oncogene. doi:10.1038/onc.2012.99. ISSN 0950-9232. 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Krauthammer, M; Kong, Y; Ha, BH; Evans, P; Bacchiocchi, A; McCusker, JP; Cheng, E; Davis, MJ; Goh, G; Choi, M; Ariyan, S; Narayan, D; Dutton-Regester, K; Capatana, A; Holman, EC; Bosenberg, M; Sznol, M; Kluger, HM; Brash, DE; Stern, DF; Materin, MA; Lo, RS; Mane, S; Ma, S; Kidd, KK; Hayward, NK; Lifton, RP; Schlessinger, J; Boggon, TJ; Halaban, R (2012 Jul 29). “Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma.”. Nature genetics. PMID 22842228. Bauer, Natalie N.; Chen, Yih-Wen; Samant, Rajeev S.; Shevde, Lalita A.; Fodstad, Oystein (2007). “Rac1 activity regulates proliferation of aggressive metastatic melanoma”. Experimental Cell Research 313 (18): 3832–3839. doi:10.1016/j.yexcr.2007.08.017. ISSN 00144827. Stallings-Mann, M. L.; Waldmann, J.; Zhang, Y.; Miller, E.; Gauthier, M. L.; Visscher, D. W.; Downey, G. P.; Radisky, E. S. et al. (2012). “Matrix Metalloproteinase Induction of Rac1b, a Key Effector of Lung Cancer Progression”. Science Translational Medicine 4 (142): 142ra95–142ra95. doi:10.1126/scitranslmed.3004062. ISSN 1946-6234. 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 (June 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. 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. Noda, Y; Takeya R, Ohno S, Naito S, Ito T, Sumimoto H (February 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 (July 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. Zhang, B; Chernoff J, Zheng Y (April 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847948/. Grizot, S; Fauré J, Fieschi F, Vignais P V, Dagher M C, Pebay-Peyroula E (August 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 (January 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. Di-Poï, N; Fauré J, Grizot S, Molnár G, Pick E, Dagher M C (August 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. Kitamura, Y; Kitamura T, Sakaue H, Maeda T, Ueno H, Nishio S, Ohno S, Osada S i, Sakaue M, Ogawa W, Kasuga M (March 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1218269/. Kuroda, S; Fukata M, Kobayashi K, Nakafuku M, Nomura N, Iwamatsu A, Kaibuchi K (September 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 (June 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. 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. 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- 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.