Serine--tRNA ligase, cytoplasmic

Definition:

Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC. Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA.

References:

[1]. Yi Shi, et al. tRNA synthetase counteracts c-Myc to develop functional vasculature. Elife. 2014 Jun 17;3:e02349. [Content Brief]

[2]. Hajime Fukui, et al. Noncanonical activity of seryl-tRNA synthetase is involved in vascular development. Circ Res. 2009 Jun 5;104(11):1253-9. [Content Brief]

[3]. Xiaoling Xu, et al. Unique domain appended to vertebrate tRNA synthetase is essential for vascular development. Nat Commun. 2012 Feb 21;3:681. [Content Brief]

[4]. Wiebke Herzog, et al. Genetic evidence for a noncanonical function of seryl-tRNA synthetase in vascular development. Circ Res. 2009 Jun 5;104(11):1260-6. [Content Brief]

[5]. C Vincent, et al. Genomic organization, cDNA sequence, bacterial expression, and purification of human seryl-tRNA synthase. Eur J Biochem. 1997 Nov 15;250(1):77-84. [Content Brief]

[6]. Caiyan Wang, et al. SerRS-tRNASec complex structures reveal mechanism of the first step in selenocysteine biosynthesis. Nucleic Acids Res. 2015 Dec 2;43(21):10534-45. [Content Brief]

[7]. Xiaoling Xu, et al. Crystal structure of human Seryl-tRNA synthetase and Ser-SA complex reveals a molecular lever specific to higher eukaryotes. Structure. 2013 Nov 5;21(11):2078-86. [Content Brief]

[8]. Luciana Musante, et al. Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. Hum Mutat. 2017 Jun;38(6):621-636. [Content Brief]

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