KARS (gene)
Lysyl-tRNA synthetase is an enzyme that in humans is encoded by the KARS gene.[1][2][3]
Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis[3]
Besides its role in translation, Lysyl-tRNA synthetase is involved in a signaling pathway leading to gene activation.[4] Following physiological stimulation of a variety of cells, Lysyl-tRNA synthetase binds to the transcription factors MITF[5] and USF2[6] and can then influence their transcriptional activities. Such physiological stimulation includes immunological activation of mast cells, so this pathway maybe relevant to the allergic response.
Interactions
KARS (gene) has been shown to interact with Multisynthetase complex auxiliary component p38.[7][8] Physiological trigger such as immunological activation results in the phosphorylation of LysRS is on serine residues. It separates from the multisynthetase complex and initiates Ap4A production.[4]
References
- ^ Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Feb 1997). "Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24". Genomics 36 (1): 210–3. doi:10.1006/geno.1996.0449. PMID 8812440.
- ^ Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (Oct 1997). "Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant". J Biol Chem 272 (36): 22809–16. doi:10.1074/jbc.272.36.22809. PMID 9278442.
- ^ a b "Entrez Gene: KARS lysyl-tRNA synthetase". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3735.
- ^ a b Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (June 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Mol Cell 34 (5): 603–11. doi:10.1016/j.molcel.2009.05.019. PMID 19524539.
- ^ Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity 20 (2): 145–51. doi:10.1016/S1074-7613(04)00020-2. PMID 14975237.
- ^ Lee YN, Razin E (Oct 2005). "Nonconventional Involvement of LysRS in the Molecular Mechanism of USF2 Transcriptional Activity in FcɛRI-Activated Mast Cells". Mol Cell Biol 25 (20): 8904–12. doi:10.1128/MCB.25.20.8904-8912.2005. PMC 1265770. PMID 16199869. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1265770.
- ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (Oct. 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- ^ Quevillon, S; Robinson J C, Berthonneau E, Siatecka M, Mirande M (Jan. 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". J. Mol. Biol. (ENGLAND) 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. ISSN 0022-2836. PMID 9878398.
Further reading
- Yannay-Cohen N, Razin E (2006). "Translation and transcription: the dual functionality of LysRS in mast cells". Mol Cells 22 (2): 127–32. PMID 17085962.
- Carmi-Levy I, Yannay-Cohen N, Kay G, Razin E, Nechushtan N (2008). "Diadenosine Tetraphosphate Hydrolase Is Part of the Transcriptional Regulation Network in Immunologically Activated Mast Cells". Mol. Cell. Biol. 28 (18): 5777–84. doi:10.1128/MCB.00106-08. PMC 2546939. PMID 18644867. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2546939.
- Carmi-Levy I, Motzik A, Ofir-Birin Y, Yagil Z, Yang CM, Kemeny DM, Han JM, Kim S, Kay G, Nechushtan H, Suzuki R, Rivera J, Razin E (2011). "Importin Beta Plays an Essential Role in the Regulation of the LysRS-Ap4A Pathway in Immunologically Activated Mast Cells". Mol. Cell. Biol. 31 (10): 2111–21. doi:10.1128/MCB.01159-10. PMC 3133347. PMID 21402779. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3133347.
- Kleiman L, Halwani R, Javanbakht H (2004). "The selective packaging and annealing of primer tRNALys3 in HIV-1". Curr. HIV Res. 2 (2): 163–75. doi:10.2174/1570162043484988. PMID 15078180.
- Kino T, Pavlakis GN (2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA Cell Biol. 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
- Kleiman L, Cen S (2005). "The tRNALys packaging complex in HIV-1". Int. J. Biochem. Cell Biol. 36 (9): 1776–86. doi:10.1016/j.biocel.2004.02.022. PMID 15183344.
- Norcum MT (1991). "Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents". J. Biol. Chem. 266 (23): 15398–405. PMID 1651330.
- Nomura N, Nagase T, Miyajima N, et al. (1995). "Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 1 (5): 223–9. doi:10.1093/dnares/1.5.223. PMID 7584044.
- Stark LA, Hay RT (1998). "Human Immunodeficiency Virus Type 1 (HIV-1) Viral Protein R (Vpr) Interacts with Lys-tRNA Synthetase: Implications for Priming of HIV-1 Reverse Transcription". J. Virol. 72 (4): 3037–44. PMC 109751. PMID 9525626. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109751.
- Quevillon S, Robinson JC, Berthonneau E, et al. (1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". J. Mol. Biol. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID 9878398.
- Tolkunova E, Park H, Xia J, et al. (2001). "The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript". J. Biol. Chem. 275 (45): 35063–9. doi:10.1074/jbc.M006265200. PMID 10952987.
- Cen S, Khorchid A, Javanbakht H, et al. (2001). "Incorporation of Lysyl-tRNA Synthetase into Human Immunodeficiency Virus Type 1". J. Virol. 75 (11): 5043–8. doi:10.1128/JVI.75.11.5043-5048.2001. PMC 114908. PMID 11333884. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=114908.
- Sang Lee J, Gyu Park S, Park H, et al. (2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochem. Biophys. Res. Commun. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
- Ahn HC, Kim S, Lee BJ (2003). "Solution structure and p43 binding of the p38 leucine zipper motif: coiled-coil interactions mediate the association between p38 and p43". FEBS Lett. 542 (1–3): 119–24. doi:10.1016/S0014-5793(03)00362-4. PMID 12729910.
- Javanbakht H, Halwani R, Cen S, et al. (2003). "The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly". J. Biol. Chem. 278 (30): 27644–51. doi:10.1074/jbc.M301840200. PMID 12756246.
- Kim MJ, Park BJ, Kang YS, et al. (2003). "Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation". Nat. Genet. 34 (3): 330–6. doi:10.1038/ng1182. PMID 12819782.
- Di Y, Li J, Zhang Y, et al. (2004). "HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins". J. Biochem. 133 (6): 713–8. doi:10.1093/jb/mvg091. PMID 12869526.