KARS (gene) explained
Lysyl-tRNA synthetase is an enzyme that in humans is encoded by the KARS gene.[1] [2] [3]
Function
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 on its serine residues. It separates from the multisynthetase complex and initiates Ap4A production.[4]
Further reading
- Yannay-Cohen N, Razin E . Translation and transcription: the dual functionality of LysRS in mast cells . Molecules and Cells . 22 . 2 . 127–32 . Oct 2006 . 10.1016/S1016-8478(23)17400-0 . 17085962 . free .
- Carmi-Levy I, Yannay-Cohen N, Kay G, Razin E, Nechushtan H . Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells . Molecular and Cellular Biology . 28 . 18 . 5777–84 . Sep 2008 . 18644867 . 2546939 . 10.1128/MCB.00106-08 .
- 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 . Importin beta plays an essential role in the regulation of the LysRS-Ap(4)A pathway in immunologically activated mast cells . Molecular and Cellular Biology . 31 . 10 . 2111–21 . May 2011 . 21402779 . 3133347 . 10.1128/MCB.01159-10 .
- Kleiman L, Halwani R, Javanbakht H . The selective packaging and annealing of primer tRNALys3 in HIV-1 . Current HIV Research . 2 . 2 . 163–75 . Apr 2004 . 15078180 . 10.2174/1570162043484988 .
- Kino T, Pavlakis GN . Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1 . DNA and Cell Biology . 23 . 4 . 193–205 . Apr 2004 . 15142377 . 10.1089/104454904773819789 .
- Kleiman L, Cen S . The tRNALys packaging complex in HIV-1 . The International Journal of Biochemistry & Cell Biology . 36 . 9 . 1776–86 . Sep 2004 . 15183344 . 10.1016/j.biocel.2004.02.022 .
- Norcum MT . Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents . The Journal of Biological Chemistry . 266 . 23 . 15398–405 . Aug 1991 . 10.1016/S0021-9258(18)98629-1 . 1651330 . free .
- Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S . 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 Research . 1 . 5 . 223–9 . 1995 . 7584044 . 10.1093/dnares/1.5.223 . free .
- Stark LA, Hay RT . Human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) interacts with Lys-tRNA synthetase: implications for priming of HIV-1 reverse transcription . Journal of Virology . 72 . 4 . 3037–44 . Apr 1998 . 9525626 . 109751 . 10.1128/JVI.72.4.3037-3044.1998.
- Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M . Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein . Journal of Molecular Biology . 285 . 1 . 183–95 . Jan 1999 . 9878398 . 10.1006/jmbi.1998.2316 .
- Tolkunova E, Park H, Xia J, King MP, Davidson E . The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript . The Journal of Biological Chemistry . 275 . 45 . 35063–9 . Nov 2000 . 10952987 . 10.1074/jbc.M006265200 . free .
- Cen S, Khorchid A, Javanbakht H, Gabor J, Stello T, Shiba K, Musier-Forsyth K, Kleiman L . Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1 . Journal of Virology . 75 . 11 . 5043–8 . Jun 2001 . 11333884 . 114908 . 10.1128/JVI.75.11.5043-5048.2001 .
- Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S . Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex . Biochemical and Biophysical Research Communications . 291 . 1 . 158–64 . Feb 2002 . 11829477 . 10.1006/bbrc.2002.6398 .
- Ahn HC, Kim S, Lee BJ . Solution structure and p43 binding of the p38 leucine zipper motif: coiled-coil interactions mediate the association between p38 and p43 . FEBS Letters . 542 . 1–3 . 119–24 . May 2003 . 12729910 . 10.1016/S0014-5793(03)00362-4 . 39222196 . free .
- Javanbakht H, Halwani R, Cen S, Saadatmand J, Musier-Forsyth K, Gottlinger H, Kleiman L . The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly . The Journal of Biological Chemistry . 278 . 30 . 27644–51 . Jul 2003 . 12756246 . 10.1074/jbc.M301840200 . free .
- Kim MJ, Park BJ, Kang YS, Kim HJ, Park JH, Kang JW, Lee SW, Han JM, Lee HW, Kim S . Downregulation of FUSE-binding protein and c-myc by tRNA synthetase cofactor p38 is required for lung cell differentiation . Nature Genetics . 34 . 3 . 330–6 . Jul 2003 . 12819782 . 10.1038/ng1182 . 41006480 .
- Di Y, Li J, Zhang Y, He X, Lu H, Xu D, Ling J, Huo K, Wan D, Li YY, Gu J . HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins . Journal of Biochemistry . 133 . 6 . 713–8 . Jun 2003 . 12869526 . 10.1093/jb/mvg091 .
Notes and References
- Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P . 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 . Aug 1996 . 8812440 . 10.1006/geno.1996.0449 .
- Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P . Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant . The Journal of Biological Chemistry . 272 . 36 . 22809–16 . Sep 1997 . 9278442 . 10.1074/jbc.272.36.22809 . free .
- Web site: Entrez Gene: KARS lysyl-tRNA synthetase.
- Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E . LysRS serves as a key signaling molecule in the immune response by regulating gene expression . Molecular Cell . 34 . 5 . 603–11 . Jun 2009 . 19524539 . 10.1016/j.molcel.2009.05.019 . free .
- Lee YN, Nechushtan H, Figov N, Razin E . The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells . Immunity . 20 . 2 . 145–51 . Feb 2004 . 14975237 . 10.1016/S1074-7613(04)00020-2 . 36723485 .
- Lee YN, Razin E . Nonconventional involvement of LysRS in the molecular mechanism of USF2 transcriptional activity in FcepsilonRI-activated mast cells . Molecular and Cellular Biology . 25 . 20 . 8904–12 . Oct 2005 . 16199869 . 1265770 . 10.1128/MCB.25.20.8904-8912.2005 .
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
- Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M . Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein . Journal of Molecular Biology . 285 . 1 . 183–95 . Jan 1999 . 9878398 . 10.1006/jmbi.1998.2316 .