KARS1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKARS1, KARS2, CMTRIB, lysyl-tRNA synthetase 1, KRS, Lysyl-tRNA synthetase, KARS, DFNB89, LEPID, DEAPLE
External IDsOMIM: 601421 MGI: 1934754 HomoloGene: 4053 GeneCards: KARS1
Orthologs
SpeciesHumanMouse
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 MbChr 8: 112.72 – 112.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000065427 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 "Entrez Gene: KARS lysyl-tRNA synthetase".
  8. 1 2 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. S2CID 36723485.
  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. Bibcode:2005Natur.437.1173R. 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

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