Lysine–tRNA ligase (also called Lysyl-tRNA synthetase) is an enzyme that in humans is encoded by the KARS1 gene (previously KARS). As a lysine–tRNA ligase, this enzyme acts to attach the amino acid lysine to the corresponding transfer RNA (tRNALys) as part of RNA-to-protein translation and protein synthesis.
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
Besides its role in translation, Lysyl-tRNA synthetase is involved in a signaling pathway leading to gene activation. Following physiological stimulation of a variety of cells, Lysyl-tRNA synthetase binds to the transcription factors MITF and USF2 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.
KARS1 has been shown to interact with Multisynthetase complex auxiliary component p38. 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.
Pathogenic (compound heterozygous) mutations in KARS1 are associated with developmental delays and peripheral nervous system disfunction, in particular, a form of Charcot-Marie-Tooth disease called recessive intermediate Charcot-Marie-Tooth disease B (CMTRIB).
