Lysyl-tRNA synthetase is an enzyme that in humans is encoded by the KARSgene.[5][6][7]
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[7]
Besides its role in translation, Lysyl-tRNA synthetase is involved in a signaling pathway leading to gene activation.[8] Following physiological stimulation of a variety of cells, Lysyl-tRNA synthetase binds to the transcription factors MITF[9] and USF2[10] 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.[11][12] 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.[8]
^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. PMID14975237. S2CID36723485.
^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 (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID16189514. S2CID4427026.
^Quevillon S, Robinson JC, 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". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID9878398.
Kleiman L, Halwani R, Javanbakht H (Apr 2004). "The selective packaging and annealing of primer tRNALys3 in HIV-1". Current HIV Research. 2 (2): 163–75. doi:10.2174/1570162043484988. PMID15078180.
Kleiman L, Cen S (Sep 2004). "The tRNALys packaging complex in HIV-1". The International Journal of Biochemistry & Cell Biology. 36 (9): 1776–86. doi:10.1016/j.biocel.2004.02.022. PMID15183344.
Quevillon S, Robinson JC, 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". Journal of Molecular Biology. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID9878398.
Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (Feb 2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochemical and Biophysical Research Communications. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID11829477.
Kim MJ, Park BJ, Kang YS, Kim HJ, Park JH, Kang JW, Lee SW, Han JM, Lee HW, Kim S (Jul 2003). "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. doi:10.1038/ng1182. PMID12819782. S2CID41006480.
Di Y, Li J, Zhang Y, He X, Lu H, Xu D, Ling J, Huo K, Wan D, Li YY, Gu J (Jun 2003). "HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins". Journal of Biochemistry. 133 (6): 713–8. doi:10.1093/jb/mvg091. PMID12869526.
