Lysine--tRNA ligase

Definition:

Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages. Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity.; (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.

References:

[1]. Yifat Ofir-Birin, et al. Structural switch of lysyl-tRNA synthetase between translation and transcription. Mol Cell. 2013 Jan 10;49(1):30-42. [Content Brief]

[2]. Sang Gyu Park, et al. Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc Natl Acad Sci U S A. 2005 May 3;102(18):6356-61. [Content Brief]

[3]. Nurit Yannay-Cohen, et al. LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol Cell. 2009 Jun 12;34(5):603-11. [Content Brief]

[4]. Xiao-Long Zhou, et al. Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: Potential pathogenic mechanism. Hum Mutat. 2017 Dec;38(12):1740-1750. [Content Brief]

[5]. Catherine M Guzzo, et al. Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase and p38 in vitro. Biochem Biophys Res Commun. 2008 Jan 25;365(4):718-23. [Content Brief]

[6]. K Shiba, et al. Human lysyl-tRNA synthetase accepts nucleotide 73 variants and rescues Escherichia coli double-defective mutant. J Biol Chem. 1997 Sep 5;272(36):22809-16. [Content Brief]

[7]. Yu-Nee Lee, et al. The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells. Immunity. 2004 Feb;20(2):145-51. [Content Brief]

[8]. Rabih Halwani, et al. Cellular distribution of Lysyl-tRNA synthetase and its interaction with Gag during human immunodeficiency virus type 1 assembly. J Virol. 2004 Jul;78(14):7553-64. [Content Brief]

[9]. Min Guo, et al. Crystal structure of tetrameric form of human lysyl-tRNA synthetase: Implications for multisynthetase complex formation. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2331-6. [Content Brief]

[10]. P C Zamecnik, et al. Enzymatic synthesis of diadenosine tetraphosphate and diadenosine triphosphate with a purified lysyl-sRNA synthetase. Biochem Biophys Res Commun. 1966 Jul 6;24(1):91-7. [Content Brief]

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