Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:28675565, PubMed:24898252). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017). ATP + glycine + tRNA(Gly) = AMP + diphosphate + glycyl-tRNA(Gly) 2 ATP + H(+) = diphosphate + P(1),P(4)-bis(5'-adenosyl) tetraphosphate Ap4A synthesis is inhibited by tRNA, via the disruption of the second ATP-binding site by direct blocking and/or by tRNA-induced conformational change. kcat is 0.049 sec(-1) for aminoacylation of tRNA(Gly). Homodimer. In transfected COS7 cells, not detected in mitochondria, nor in Golgi apparatus (PubMed:17035524). Secreted by motor neuron, possibly through the exosome pathway (By similarity). Widely expressed, including in brain and spinal cord. Expressed in brain, spinal cord, muscle, heart and spleen. Expressed in brain, spinal cord, muscle, heart, spleen and liver. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Human GlyRS uses direct ATP condensation to synthesize Ap4A, a unique amino acid-independent mechanism, in contrast to the classical amino acid-dependent mechanism for synthesis of Ap4A by a tRNA synthetase, that involves the generation of an enzyme-bound aminoacyl-AMP which is then attacked by ATP to form Ap4A. The isoform 2 translation is regulated by an Internal Ribosome Entry Site (IRES) and an upstream Open Reading Frame. Both are important in hindering the synthesis of the mitochondrial GARS and target the translation of the cytosolic enzyme to ER-bound ribosomes. Belongs to the class-II aminoacyl-tRNA synthetase family. According to a report, variant Leu-635 induces reduced activity (PubMed:17544401). According to another report, it does not affect function (PubMed:25168514). Truncated N-terminus. Truncated N-terminus.