Glycine–tRNA ligase

This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases.^[7]

In enzymology, a glycine–tRNA ligase (EC 6.1.1.14) is an enzyme that catalyzes the chemical reaction

ATP + glycine + tRNA^Gly ${\displaystyle \rightleftharpoons }$ AMP + diphosphate + glycyl-tRNA^Gly

The 3 substrates of this enzyme are ATP, glycine, and tRNA^Gly, whereas its 3 products are AMP, diphosphate, and glycyl-tRNA^Gly.

This enzyme belongs to the family of ligases, to be specific those forming carbon–oxygen bonds in aminoacyl-tRNA and related compounds. The systematic name of this enzyme class is glycine:tRNA^Gly ligase (AMP-forming). Other names in common use include glycyl-tRNA synthetase, glycyl-transfer ribonucleate synthetase, glycyl-transfer RNA synthetase, glycyl-transfer ribonucleic acid synthetase, and glycyl translase. This enzyme participates in glycine, serine and threonine metabolism and aminoacyl-tRNA biosynthesis.

Glycyl-tRNA synthetase has been shown to interact with EEF1D.^[8] Mutant forms of the protein associated with peripheral nerve disease have been shown to aberrantly bind to the transmembrane receptor proteins neuropilin 1^[9] and Trk receptors A-C.^[10]

Glycyl-tRNA synthetase has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis.^[7]

The peripheral nerve diseases Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) have been liked to dominant mutations in GARS.^[11][12] CMT2D usually manifests during the teenage years, and results in muscle weakness predominantly in the hands and feet.^[13] Two mouse models of CMT2D have been used to better understand the disease, identifying that the disorder is caused by a toxic gain-of-function of the mutant glycine-tRNA ligase protein.^[14] The CMT2D mice display peripheral nerve axon degeneration ^[15][16] and defective development^[17] and function^[18] of the neuromuscular junction.