KARS (gene)

Lysyl-tRNA synthetase
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3BJU​, 4DPG​
Identifiers
Symbols	KARS ; CMTRIB; DFNB89; KARS1; KARS2; KRS
External IDs	OMIM: 601421 MGI: 1934754 HomoloGene: 4053 ChEMBL: 5575 GeneCards: KARS Gene
EC number	6.1.1.6
Gene ontology Molecular function • tRNA binding • lysine-tRNA ligase activity • protein binding • ATP binding • amino acid binding • metal ion binding Cellular component • extracellular region • nucleus • cytoplasm • mitochondrion • mitochondrial matrix • cytosol • plasma membrane • microtubule cytoskeleton • aminoacyl-tRNA synthetase multienzyme complex Biological process • tRNA aminoacylation for protein translation • lysyl-tRNA aminoacylation • tRNA processing • gene expression • diadenosine tetraphosphate biosynthetic process • viral process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3735	85305
Ensembl	ENSG00000065427	ENSMUSG00000031948
UniProt	Q15046	Q99MN1
RefSeq (mRNA)	NM_001130089	NM_001130868
RefSeq (protein)	NP_001123561	NP_001124340
Location (UCSC)	Chr 16: 75.63 – 75.65 Mb	Chr 8: 111.99 – 112.01 Mb
PubMed search

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 is on serine residues. It separates from the multisynthetase complex and initiates Ap4A production.^[4]

References

1. Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Aug 1996). "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.
2. Shiba K, Stello T, Motegi H, Noda T, Musier-Forsyth K, Schimmel P (Sep 1997). "Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant". The Journal of Biological Chemistry 272 (36): 22809–16. doi:10.1074/jbc.272.36.22809. PMID 9278442.
3. "Entrez Gene: KARS lysyl-tRNA synthetase".
4. Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (Jun 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Molecular Cell 34 (5): 603–11. doi:10.1016/j.molcel.2009.05.019. PMID 19524539.
5. 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.
6. Lee YN, Razin E (Oct 2005). "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. doi:10.1128/MCB.25.20.8904-8912.2005. PMC 1265770. PMID 16199869.
7. 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. doi:10.1038/nature04209. PMID 16189514.
8. 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. PMID 9878398.

Further reading

• Yannay-Cohen N, Razin E (Oct 2006). "Translation and transcription: the dual functionality of LysRS in mast cells". Molecules and Cells 22 (2): 127–32. PMID 17085962.
• Carmi-Levy I, Yannay-Cohen N, Kay G, Razin E, Nechushtan H (Sep 2008). "Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells". Molecular and Cellular Biology 28 (18): 5777–84. doi:10.1128/MCB.00106-08. PMC 2546939. PMID 18644867.
• 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 (May 2011). "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. doi:10.1128/MCB.01159-10. PMC 3133347. PMID 21402779.
• 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. PMID 15078180.
• Kino T, Pavlakis GN (Apr 2004). "Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1". DNA and Cell Biology 23 (4): 193–205. doi:10.1089/104454904773819789. PMID 15142377.
• 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. PMID 15183344.
• Norcum MT (Aug 1991). "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. PMID 1651330.
• Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S (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 Research 1 (5): 223–9. doi:10.1093/dnares/1.5.223. PMID 7584044.
• Stark LA, Hay RT (Apr 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". Journal of Virology 72 (4): 3037–44. PMC 109751. PMID 9525626.
• 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. PMID 9878398.
• Tolkunova E, Park H, Xia J, King MP, Davidson E (Nov 2000). "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. doi:10.1074/jbc.M006265200. PMID 10952987.
• Cen S, Khorchid A, Javanbakht H, Gabor J, Stello T, Shiba K, Musier-Forsyth K, Kleiman L (Jun 2001). "Incorporation of lysyl-tRNA synthetase into human immunodeficiency virus type 1". Journal of Virology 75 (11): 5043–8. doi:10.1128/JVI.75.11.5043-5048.2001. PMC 114908. PMID 11333884.
• 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. PMID 11829477.
• Ahn HC, Kim S, Lee BJ (May 2003). "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. doi:10.1016/S0014-5793(03)00362-4. PMID 12729910.
• Javanbakht H, Halwani R, Cen S, Saadatmand J, Musier-Forsyth K, Gottlinger H, Kleiman L (Jul 2003). "The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly". The Journal of Biological Chemistry 278 (30): 27644–51. doi:10.1074/jbc.M301840200. PMID 12756246.
• 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. PMID 12819782.
• 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. PMID 12869526.