KARS (gene)

Lysyl-tRNA synthetase is an enzyme that in humans is encoded by the KARS gene.[5][6][7]

KARS1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3BJU, 4DPG, 4YCU, 4YCW
Identifiers
Aliases	KARS1, CMTRIB, DFNB89, KARS2, KRS, Lysyl-tRNA synthetase, KARS, lysyl-tRNA synthetase 1
External IDs	OMIM: 601421 MGI: 1934754 HomoloGene: 4053 GeneCards: KARS1
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q23.1 Start 75,627,474 bp[1] End 75,648,643 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 E1|8 58.27 cM Start 111,993,443 bp[2] End 112,011,323 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • aminoacyl-tRNA ligase activity • nucleotide binding • amino acid binding • tRNA binding • lysine-tRNA ligase activity • ligase activity • GO:0001948 protein binding • nucleic acid binding • ATP binding • ATP adenylyltransferase activity • protein homodimerization activity • transferase activity • identical protein binding Cellular component • membrane • cell membrane • extracellular region • mitochondrial matrix • mitochondrion • extracellular • aminoacyl-tRNA synthetase multienzyme complex • cell nucleus • cytoplasm • cytosol Biological process • protein biosynthesis • tRNA processing • tRNA aminoacylation for protein translation • lysyl-tRNA aminoacylation • GO:0022415 viral process • activation of MAPK activity • basophil activation involved in immune response • negative regulation of cell proliferation • positive regulation of macrophage chemotaxis • tumor necrosis factor-mediated signaling pathway • positive regulation of macrophage activation • positive regulation of transcription, DNA-templated • ERK1 and ERK2 cascade • positive regulation of ERK1 and ERK2 cascade • positive regulation of cytokine production involved in inflammatory response • positive regulation of p38MAPK cascade • positive regulation of metallopeptidase activity • diadenosine tetraphosphate biosynthetic process • response to X-ray Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3735	85305
Ensembl	ENSG00000065427	ENSMUSG00000031948
UniProt	Q15046	Q99MN1
RefSeq (mRNA)	NM_005548 NM_001130089 NM_001378148	NM_001130868 NM_001286384 NM_053092 NM_001363429 NM_001363430
RefSeq (protein)	NP_001123561 NP_005539 NP_001365077	NP_001124340 NP_001273313 NP_444322 NP_001350358 NP_001350359
Location (UCSC)	Chr 16: 75.63 – 75.65 Mb	Chr 8: 111.99 – 112.01 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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]

References

1. GRCh38: Ensembl release 89: ENSG00000065427 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031948 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: KARS lysyl-tRNA synthetase".
8. 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.
9. 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.
10. 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.
11. 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. S2CID 4427026.
12. 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. doi:10.1128/JVI.72.4.3037-3044.1998. 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. S2CID 39222196.
• 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. S2CID 41006480.
• 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.