ID SYG_HUMAN Reviewed; 739 AA. AC P41250; B3KQA2; B4DIA0; Q969Y1; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 16-SEP-2015, entry version 163. DE RecName: Full=Glycine--tRNA ligase; DE EC=6.1.1.14 {ECO:0000269|PubMed:17544401}; DE AltName: Full=Diadenosine tetraphosphate synthetase; DE Short=AP-4-A synthetase; DE AltName: Full=Glycyl-tRNA synthetase; DE Short=GlyRS; GN Name=GARS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-42. RX PubMed=7962006; RA Shiba K., Schimmel P., Motegi H., Noda T.; RT "Human glycyl-tRNA synthetase. Wide divergence of primary structure RT from bacterial counterpart and species-specific aminoacylation."; RL J. Biol. Chem. 269:30049-30055(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ALA-42. RX PubMed=7753621; DOI=10.1093/nar/23.8.1307; RA Williams J.H., Osvath S.R., Khong T.-F., Pearse M.J., Power D.A.; RT "Cloning, sequencing and bacterial expression of human glycine tRNA RT synthetase."; RL Nucleic Acids Res. 23:1307-1310(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-42. RC TISSUE=Embryo, and Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-42. RC TISSUE=Eye, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-739, AND VARIANT ALA-42. RX PubMed=7961834; RA Ge Q., Trieu E.P., Targoff I.N.; RT "Primary structure and functional expression of human glycyl-tRNA RT synthetase, an autoantigen in myositis."; RL J. Biol. Chem. 269:28790-28797(1994). RN [7] RP SUBCELLULAR LOCATION. RX PubMed=9524218; DOI=10.1016/S0378-1119(98)00007-9; RA Mudge S.J., Williams J.H., Eyre H.J., Sutherland G.R., Cowan P.J., RA Power D.A.; RT "Complex organisation of the 5'-end of the human glycine tRNA RT synthetase gene."; RL Gene 209:45-50(1998). RN [8] RP SUBCELLULAR LOCATION, VARIANTS CMT2D GLY-125 AND ARG-294, RP CHARACTERIZATION OF VARIANTS CMT2D GLY-125 AND ARG-294, VARIANTS HMN5A RP PRO-183; ARG-472 AND ARG-580, AND CHARACTERIZATION OF VARIANTS HMN5A RP PRO-183; ARG-472 AND ARG-580. RX PubMed=17035524; DOI=10.1523/JNEUROSCI.1671-06.2006; RA Antonellis A., Lee-Lin S.Q., Wasterlain A., Leo P., Quezado M., RA Goldfarb L.G., Myung K., Burgess S., Fischbeck K.H., Green E.D.; RT "Functional analyses of glycyl-tRNA synthetase mutations suggest a key RT role for tRNA-charging enzymes in peripheral axons."; RL J. Neurosci. 26:10397-10406(2006). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-204 AND LYS-501, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP SUBCELLULAR LOCATION, VARIANTS CMT2D VAL-111; ASN-200; PHE-265; RP ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652, RP VARIANT LEU-635, CHARACTERIZATION OF VARIANTS CMT2D VAL-111; GLY-125; RP PRO-183; ASN-200; PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; RP ASN-554; ARG-580 AND ALA-652, AND CHARACTERIZATION OF VARIANT LEU-635. RX PubMed=25168514; DOI=10.1002/humu.22681; RA Griffin L.B., Sakaguchi R., McGuigan D., Gonzalez M.A., Searby C., RA Zuchner S., Hou Y.M., Antonellis A.; RT "Impaired function is a common feature of neuropathy-associated RT glycyl-tRNA synthetase mutations."; RL Hum. Mutat. 35:1363-1371(2014). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 55-739, FUNCTION, SUBUNIT, RP CHARACTERIZATION OF VARIANT LEU-635, CATALYTIC ACTIVITY, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=17544401; DOI=10.1016/j.febslet.2007.05.046; RA Cader M.Z., Ren J., James P.A., Bird L.E., Talbot K., Stammers D.K.; RT "Crystal structure of human wildtype and S581L-mutant glycyl-tRNA RT synthetase, an enzyme underlying distal spinal muscular atrophy."; RL FEBS Lett. 581:2959-2964(2007). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 55-739, VARIANT ARG-580, AND RP SUBUNIT. RX PubMed=17545306; DOI=10.1073/pnas.0703908104; RA Xie W., Nangle L.A., Zhang W., Schimmel P., Yang X.-L.; RT "Long-range structural effects of a Charcot-Marie-Tooth disease- RT causing mutation in human glycyl-tRNA synthetase."; RL Proc. Natl. Acad. Sci. U.S.A. 104:9976-9981(2007). RN [15] RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 55-739 IN COMPLEX WITH ATP; RP SUBSTRATE AND SUBSTRATE ANALOGS, AND FUNCTION. RX PubMed=19710017; DOI=10.1074/jbc.M109.030692; RA Guo R.-T., Chong Y.E., Guo M., Yang X.-L.; RT "Crystal structures and biochemical analyses suggest a unique RT mechanism and role for human glycyl-tRNA synthetase in Ap4A RT homeostasis."; RL J. Biol. Chem. 284:28968-28976(2009). RN [16] RP VARIANTS CMT2D GLY-125 AND ARG-294, VARIANTS HMN5A PRO-183 AND RP ARG-580, AND TISSUE SPECIFICITY. RX PubMed=12690580; DOI=10.1086/375039; RA Antonellis A., Ellsworth R.E., Sambuughin N., Puls I., Abel A., RA Lee-Lin S.Q., Jordanova A., Kremensky I., Christodoulou K., RA Middleton L.T., Sivakumar K., Ionasescu V., Funalot B., Vance J.M., RA Goldfarb L.G., Fischbeck K.H., Green E.D.; RT "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type RT 2D and distal spinal muscular atrophy type V."; RL Am. J. Hum. Genet. 72:1293-1299(2003). RN [17] RP VARIANT HMN5A ARG-472. RX PubMed=24627108; DOI=10.1007/s00415-014-7289-8; RA Schabhuettl M., Wieland T., Senderek J., Baets J., Timmerman V., RA De Jonghe P., Reilly M.M., Stieglbauer K., Laich E., Windhager R., RA Erwa W., Trajanoski S., Strom T.M., Auer-Grumbach M.; RT "Whole-exome sequencing in patients with inherited neuropathies: RT outcome and challenges."; RL J. Neurol. 261:970-982(2014). CC -!- FUNCTION: Catalyzes the attachment of glycine to tRNA(Gly). Is CC also able produce diadenosine tetraphosphate (Ap4A), a universal CC pleiotropic signaling molecule needed for cell regulation CC pathways, by direct condensation of 2 ATPs. CC {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:19710017}. CC -!- CATALYTIC ACTIVITY: ATP + glycine + tRNA(Gly) = AMP + diphosphate CC + glycyl-tRNA(Gly). {ECO:0000269|PubMed:17544401}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.3 uM for tRNA(Gly(GCC)) {ECO:0000269|PubMed:17544401}; CC KM=15 uM for glycine {ECO:0000269|PubMed:17544401}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17544401, CC ECO:0000269|PubMed:17545306, ECO:0000269|PubMed:19710017}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9524218}. CC Mitochondrion {ECO:0000269|PubMed:9524218}. Cell projection, axon CC {ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:25168514}. CC Note=Associated with granules in cultured neuron cells. CC {ECO:0000269|PubMed:17035524}. CC -!- TISSUE SPECIFICITY: Widely expressed, including brain and spinal CC cord. {ECO:0000269|PubMed:12690580}. CC -!- DISEASE: Charcot-Marie-Tooth disease 2D (CMT2D) [MIM:601472]: A CC dominant axonal form of Charcot-Marie-Tooth disease, a disorder of CC the peripheral nervous system, characterized by progressive CC weakness and atrophy, initially of the peroneal muscles and later CC of the distal muscles of the arms. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathies (designated CMT1 when they are dominantly inherited) CC and primary peripheral axonal neuropathies (CMT2). Neuropathies of CC the CMT2 group are characterized by signs of axonal degeneration CC in the absence of obvious myelin alterations, normal or slightly CC reduced nerve conduction velocities, and progressive distal muscle CC weakness and atrophy. Nerve conduction velocities are normal or CC slightly reduced. {ECO:0000269|PubMed:12690580}. Note=The disease CC is caused by mutations affecting the gene represented in this CC entry. CC -!- DISEASE: Neuronopathy, distal hereditary motor, 5A (HMN5A) CC [MIM:600794]: A disorder characterized by distal muscular atrophy CC mainly affecting the upper extremities, in contrast to other CC distal motor neuronopathies. These constitute a heterogeneous CC group of neuromuscular diseases caused by selective degeneration CC of motor neurons in the anterior horn of the spinal cord, without CC sensory deficit in the posterior horn. The overall clinical CC picture consists of a classical distal muscular atrophy syndrome CC in the legs without clinical sensory loss. The disease starts with CC weakness and wasting of distal muscles of the anterior tibial and CC peroneal compartments of the legs. Later on, weakness and atrophy CC may expand to the proximal muscles of the lower limbs and/or to CC the distal upper limbs. {ECO:0000269|PubMed:12690580, CC ECO:0000269|PubMed:24627108}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 WHEP-TRS domain. {ECO:0000255|PROSITE- CC ProRule:PRU00531}. CC -!- CAUTION: According to a report, variant Leu-635 induces reduced CC activity (PubMed:17544401). According to another report, it does CC not affect function (PubMed:25168514). CC {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:25168514}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA57001.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAA86443.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="http://www.molgen.ua.ac.be/CMTMutations/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D30658; BAA06338.1; -; mRNA. DR EMBL; U09510; AAA86443.1; ALT_INIT; mRNA. DR EMBL; AK074524; BAG51964.1; -; mRNA. DR EMBL; AK295490; BAG58412.1; -; mRNA. DR EMBL; AC005154; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006969; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004976; AAC71652.1; -; Genomic_DNA. DR EMBL; BC007722; AAH07722.1; -; mRNA. DR EMBL; BC007755; AAH07755.1; -; mRNA. DR EMBL; U09587; AAA57001.1; ALT_INIT; mRNA. DR CCDS; CCDS43564.1; -. DR PIR; A55314; A55314. DR RefSeq; NP_002038.2; NM_002047.2. DR UniGene; Hs.404321; -. DR PDB; 2PME; X-ray; 2.90 A; A=55-739. DR PDB; 2PMF; X-ray; 2.85 A; A=55-739. DR PDB; 2Q5H; X-ray; 3.00 A; A=55-739. DR PDB; 2Q5I; X-ray; 2.80 A; A=55-739. DR PDB; 2ZT5; X-ray; 2.50 A; A=55-739. DR PDB; 2ZT6; X-ray; 3.08 A; A=55-739. DR PDB; 2ZT7; X-ray; 2.70 A; A=55-739. DR PDB; 2ZT8; X-ray; 3.35 A; A=55-739. DR PDB; 2ZXF; X-ray; 3.40 A; A=55-739. DR PDB; 4KQE; X-ray; 2.74 A; A=55-739. DR PDB; 4KR2; X-ray; 3.29 A; A=114-739. DR PDB; 4KR3; X-ray; 3.24 A; A=114-739. DR PDB; 4QEI; X-ray; 2.88 A; A=118-739. DR PDBsum; 2PME; -. DR PDBsum; 2PMF; -. DR PDBsum; 2Q5H; -. DR PDBsum; 2Q5I; -. DR PDBsum; 2ZT5; -. DR PDBsum; 2ZT6; -. DR PDBsum; 2ZT7; -. DR PDBsum; 2ZT8; -. DR PDBsum; 2ZXF; -. DR PDBsum; 4KQE; -. DR PDBsum; 4KR2; -. DR PDBsum; 4KR3; -. DR PDBsum; 4QEI; -. DR ProteinModelPortal; P41250; -. DR SMR; P41250; 117-728. DR BioGrid; 108887; 54. DR DIP; DIP-50471N; -. DR IntAct; P41250; 8. DR MINT; MINT-1395438; -. DR STRING; 9606.ENSP00000373918; -. DR DrugBank; DB00145; Glycine. DR PhosphoSite; P41250; -. DR BioMuta; GARS; -. DR DMDM; 313104283; -. DR MaxQB; P41250; -. DR PaxDb; P41250; -. DR PRIDE; P41250; -. DR DNASU; 2617; -. DR Ensembl; ENST00000389266; ENSP00000373918; ENSG00000106105. DR GeneID; 2617; -. DR KEGG; hsa:2617; -. DR UCSC; uc003tbm.3; human. DR CTD; 2617; -. DR GeneCards; GC07P030594; -. DR GeneReviews; GARS; -. DR H-InvDB; HIX0006570; -. DR HGNC; HGNC:4162; GARS. DR HPA; HPA017896; -. DR HPA; HPA019097; -. DR MIM; 600287; gene. DR MIM; 600794; phenotype. DR MIM; 601472; phenotype. DR neXtProt; NX_P41250; -. DR Orphanet; 99938; Autosomal dominant Charcot-Marie-Tooth disease type 2D. DR Orphanet; 139536; Distal hereditary motor neuropathy type 5. DR PharmGKB; PA28575; -. DR eggNOG; COG0423; -. DR GeneTree; ENSGT00390000016949; -. DR HOGENOM; HOG000242015; -. DR HOVERGEN; HBG036190; -. DR InParanoid; P41250; -. DR KO; K01880; -. DR OMA; ERFGWVE; -. DR OrthoDB; EOG7FBRH1; -. DR PhylomeDB; P41250; -. DR TreeFam; TF343504; -. DR BRENDA; 6.1.1.14; 2681. DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation. DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation. DR ChiTaRS; GARS; human. DR EvolutionaryTrace; P41250; -. DR GeneWiki; Glycine%E2%80%94tRNA_ligase; -. DR GenomeRNAi; 2617; -. DR NextBio; 10303; -. DR PMAP-CutDB; P41250; -. DR PRO; PR:P41250; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; P41250; -. DR CleanEx; HS_GARS; -. DR ExpressionAtlas; P41250; baseline and differential. DR Genevisible; P41250; HS. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0030141; C:secretory granule; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004820; F:glycine-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB. DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0006426; P:glycyl-tRNA aminoacylation; IBA:GO_Central. DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. DR Gene3D; 1.10.287.10; -; 1. DR Gene3D; 3.40.50.800; -; 1. DR InterPro; IPR002314; aa-tRNA-synt_IIb. DR InterPro; IPR006195; aa-tRNA-synth_II. DR InterPro; IPR004154; Anticodon-bd. DR InterPro; IPR027031; Gly-tRNA_synthase/POLG2. DR InterPro; IPR009068; S15_NS1_RNA-bd. DR InterPro; IPR002315; tRNA-synt_gly. DR InterPro; IPR000738; WHEP-TRS_dom. DR PANTHER; PTHR10745; PTHR10745; 1. DR Pfam; PF03129; HGTP_anticodon; 1. DR Pfam; PF00587; tRNA-synt_2b; 1. DR Pfam; PF00458; WHEP-TRS; 1. DR PRINTS; PR01043; TRNASYNTHGLY. DR SMART; SM00991; WHEP-TRS; 1. DR SUPFAM; SSF47060; SSF47060; 1. DR SUPFAM; SSF52954; SSF52954; 1. DR TIGRFAMs; TIGR00389; glyS_dimeric; 1. DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1. DR PROSITE; PS00762; WHEP_TRS_1; 1. DR PROSITE; PS51185; WHEP_TRS_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; KW Cell projection; Charcot-Marie-Tooth disease; Complete proteome; KW Cytoplasm; Disease mutation; Ligase; Mitochondrion; Neurodegeneration; KW Neuropathy; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; KW Reference proteome. FT CHAIN 1 739 Glycine--tRNA ligase. FT /FTId=PRO_0000072998. FT DOMAIN 63 119 WHEP-TRS. {ECO:0000255|PROSITE- FT ProRule:PRU00531}. FT NP_BIND 331 333 ATP. {ECO:0000269|PubMed:19710017}. FT NP_BIND 341 346 ATP. {ECO:0000269|PubMed:19710017}. FT NP_BIND 457 458 ATP. {ECO:0000269|PubMed:19710017}. FT NP_BIND 580 583 ATP. {ECO:0000269|PubMed:19710017}. FT REGION 346 350 Substrate binding. FT REGION 576 580 Substrate binding. FT BINDING 213 213 Substrate. {ECO:0000269|PubMed:19710017}. FT BINDING 299 299 Substrate. {ECO:0000269|PubMed:19710017}. FT BINDING 435 435 Substrate; via carbonyl oxygen. FT {ECO:0000269|PubMed:19710017}. FT MOD_RES 204 204 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 453 453 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q9CZD3}. FT MOD_RES 501 501 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VARIANT 42 42 P -> A (in dbSNP:rs1049402). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7753621, FT ECO:0000269|PubMed:7961834, FT ECO:0000269|PubMed:7962006}. FT /FTId=VAR_054865. FT VARIANT 111 111 A -> V (in CMT2D; shows a reduction in FT aminoacylation activity). FT {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073187. FT VARIANT 125 125 E -> G (in CMT2D; phenotype overlapping FT with DSMA-V; complements the defect of FT the wild-type gene in yeast; FT dbSNP:rs28936972). FT {ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, FT ECO:0000269|PubMed:25168514}. FT /FTId=VAR_018718. FT VARIANT 183 183 L -> P (in HMN5A; does not complement the FT defect of the wild-type gene in yeast). FT {ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, FT ECO:0000269|PubMed:25168514}. FT /FTId=VAR_018719. FT VARIANT 200 200 D -> N (in CMT2D; shows a large reduction FT in aminoacylation activity). FT {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073188. FT VARIANT 265 265 S -> F (in CMT2D; shows a large reduction FT in aminoacylation activity; demonstrates FT a change in the subcellular location FT pattern; does not associate with FT granules). {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073189. FT VARIANT 268 268 T -> I (in dbSNP:rs2230310). FT /FTId=VAR_054866. FT VARIANT 294 294 G -> R (in CMT2D; shows a large reduction FT in aminoacylation activity; does not FT impair transcription or translation or FT protein stability). FT {ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, FT ECO:0000269|PubMed:25168514}. FT /FTId=VAR_018720. FT VARIANT 298 298 P -> L (in CMT2D; shows a large reduction FT in aminoacylation activity; demonstrates FT a change in subcellular location pattern; FT does not associate with granules). FT {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073190. FT VARIANT 334 334 I -> F (in CMT2D; shows a large reduction FT in aminoacylation activity; demonstrates FT a change in subcellular location pattern; FT does not associate with granules). FT {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073191. FT VARIANT 388 388 R -> Q (in dbSNP:rs17159287). FT /FTId=VAR_054867. FT VARIANT 472 472 H -> R (in HMN5A; shows a large reduction FT in aminoacylation activity; does not FT complement the defect of the wild-type FT gene in yeast). FT {ECO:0000269|PubMed:17035524, FT ECO:0000269|PubMed:24627108, FT ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073192. FT VARIANT 554 554 D -> N (in CMT2D; demonstrates no change FT in subcellular location pattern). FT {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073193. FT VARIANT 580 580 G -> R (in HMN5A; higher dimerization FT stability; loss of activity; shows a FT large reduction in aminoacylation FT activity; dbSNP:rs28937323). FT {ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, FT ECO:0000269|PubMed:17545306, FT ECO:0000269|PubMed:25168514}. FT /FTId=VAR_018721. FT VARIANT 635 635 S -> L (polymorphism; has no effect on FT subcellular localization; results in FT reduced activity). FT {ECO:0000269|PubMed:17544401, FT ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073194. FT VARIANT 652 652 G -> A (in CMT2D; shows a large reduction FT in aminoacylation activity; demonstrates FT a change in subcellular location pattern; FT does not associate with granules). FT {ECO:0000269|PubMed:25168514}. FT /FTId=VAR_073195. FT CONFLICT 9 18 Missing (in Ref. 3; BAG58412). FT {ECO:0000305}. FT CONFLICT 205 205 D -> G (in Ref. 3; BAG51964). FT {ECO:0000305}. FT CONFLICT 530 530 M -> I (in Ref. 2; AAA86443). FT {ECO:0000305}. FT CONFLICT 634 634 L -> S (in Ref. 3; BAG51964). FT {ECO:0000305}. FT HELIX 121 130 {ECO:0000244|PDB:2ZT5}. FT STRAND 133 136 {ECO:0000244|PDB:2ZT5}. FT HELIX 139 141 {ECO:0000244|PDB:2ZT5}. FT STRAND 148 150 {ECO:0000244|PDB:2ZT5}. FT HELIX 152 168 {ECO:0000244|PDB:2ZT5}. FT HELIX 170 173 {ECO:0000244|PDB:2ZT5}. FT STRAND 182 185 {ECO:0000244|PDB:2ZT5}. FT HELIX 186 191 {ECO:0000244|PDB:2ZT5}. FT HELIX 194 197 {ECO:0000244|PDB:2ZT5}. FT STRAND 199 208 {ECO:0000244|PDB:2ZT5}. FT STRAND 211 213 {ECO:0000244|PDB:2ZT5}. FT HELIX 214 227 {ECO:0000244|PDB:2ZT5}. FT STRAND 229 231 {ECO:0000244|PDB:2Q5I}. FT HELIX 233 243 {ECO:0000244|PDB:2ZT5}. FT TURN 244 248 {ECO:0000244|PDB:2ZT5}. FT HELIX 251 260 {ECO:0000244|PDB:2ZT5}. FT STRAND 266 268 {ECO:0000244|PDB:2ZT5}. FT STRAND 276 279 {ECO:0000244|PDB:2ZT5}. FT STRAND 283 285 {ECO:0000244|PDB:2ZT5}. FT STRAND 287 296 {ECO:0000244|PDB:2ZT5}. FT STRAND 298 300 {ECO:0000244|PDB:2ZXF}. FT HELIX 301 305 {ECO:0000244|PDB:2ZT5}. FT HELIX 308 314 {ECO:0000244|PDB:2ZT5}. FT TURN 315 317 {ECO:0000244|PDB:2ZT5}. FT STRAND 321 330 {ECO:0000244|PDB:2ZT5}. FT HELIX 339 341 {ECO:0000244|PDB:2ZT5}. FT STRAND 344 355 {ECO:0000244|PDB:2ZT5}. FT HELIX 357 359 {ECO:0000244|PDB:4KQE}. FT HELIX 365 367 {ECO:0000244|PDB:2ZT5}. FT TURN 368 370 {ECO:0000244|PDB:2ZT5}. FT STRAND 372 376 {ECO:0000244|PDB:2ZT5}. FT HELIX 378 382 {ECO:0000244|PDB:2ZT5}. FT STRAND 388 391 {ECO:0000244|PDB:2ZT5}. FT HELIX 392 397 {ECO:0000244|PDB:2ZT5}. FT STRAND 400 402 {ECO:0000244|PDB:2PME}. FT HELIX 404 420 {ECO:0000244|PDB:2ZT5}. FT HELIX 424 426 {ECO:0000244|PDB:2ZT5}. FT STRAND 427 431 {ECO:0000244|PDB:2ZT5}. FT HELIX 434 436 {ECO:0000244|PDB:2ZT5}. FT STRAND 442 451 {ECO:0000244|PDB:2ZT5}. FT STRAND 454 462 {ECO:0000244|PDB:2ZT5}. FT HELIX 467 476 {ECO:0000244|PDB:2ZT5}. FT STRAND 482 484 {ECO:0000244|PDB:2ZT5}. FT HELIX 501 507 {ECO:0000244|PDB:4KQE}. FT HELIX 512 519 {ECO:0000244|PDB:4KQE}. FT HELIX 524 535 {ECO:0000244|PDB:4KQE}. FT STRAND 541 544 {ECO:0000244|PDB:4KQE}. FT STRAND 547 550 {ECO:0000244|PDB:4KQE}. FT STRAND 552 554 {ECO:0000244|PDB:4KQE}. FT STRAND 562 564 {ECO:0000244|PDB:2PMF}. FT TURN 565 567 {ECO:0000244|PDB:2PMF}. FT STRAND 568 570 {ECO:0000244|PDB:2ZT5}. FT STRAND 573 580 {ECO:0000244|PDB:2ZT5}. FT HELIX 581 592 {ECO:0000244|PDB:2ZT5}. FT STRAND 593 595 {ECO:0000244|PDB:2ZT5}. FT STRAND 597 600 {ECO:0000244|PDB:4KQE}. FT STRAND 603 605 {ECO:0000244|PDB:2ZT5}. FT TURN 609 611 {ECO:0000244|PDB:2ZT5}. FT STRAND 615 621 {ECO:0000244|PDB:2ZT5}. FT TURN 625 627 {ECO:0000244|PDB:2ZT5}. FT HELIX 628 640 {ECO:0000244|PDB:2ZT5}. FT STRAND 645 647 {ECO:0000244|PDB:2ZT5}. FT STRAND 650 652 {ECO:0000244|PDB:4KR3}. FT HELIX 654 663 {ECO:0000244|PDB:2ZT5}. FT STRAND 668 672 {ECO:0000244|PDB:2ZT5}. FT HELIX 674 677 {ECO:0000244|PDB:2ZT5}. FT STRAND 679 681 {ECO:0000244|PDB:2ZT5}. FT STRAND 683 688 {ECO:0000244|PDB:2ZT5}. FT TURN 689 691 {ECO:0000244|PDB:2ZT5}. FT STRAND 694 698 {ECO:0000244|PDB:2ZT5}. FT TURN 699 701 {ECO:0000244|PDB:2ZT5}. FT HELIX 702 710 {ECO:0000244|PDB:2ZT5}. FT STRAND 712 714 {ECO:0000244|PDB:4KR3}. FT HELIX 716 722 {ECO:0000244|PDB:2ZT5}. SQ SEQUENCE 739 AA; 83166 MW; E4C001CEBF985C59 CRC64; MPSPRPVLLR GARAALLLLL PPRLLARPSL LLRRSLSAAS CPPISLPAAA SRSSMDGAGA EEVLAPLRLA VRQQGDLVRK LKEDKAPQVD VDKAVAELKA RKRVLEAKEL ALQPKDDIVD RAKMEDTLKR RFFYDQAFAI YGGVSGLYDF GPVGCALKNN IIQTWRQHFI QEEQILEIDC TMLTPEPVLK TSGHVDKFAD FMVKDVKNGE CFRADHLLKA HLQKLMSDKK CSVEKKSEME SVLAQLDNYG QQELADLFVN YNVKSPITGN DLSPPVSFNL MFKTFIGPGG NMPGYLRPET AQGIFLNFKR LLEFNQGKLP FAAAQIGNSF RNEISPRSGL IRVREFTMAE IEHFVDPSEK DHPKFQNVAD LHLYLYSAKA QVSGQSARKM RLGDAVEQGV INNTVLGYFI GRIYLYLTKV GISPDKLRFR QHMENEMAHY ACDCWDAESK TSYGWIEIVG CADRSCYDLS CHARATKVPL VAEKPLKEPK TVNVVQFEPS KGAIGKAYKK DAKLVMEYLA ICDECYITEM EMLLNEKGEF TIETEGKTFQ LTKDMINVKR FQKTLYVEEV VPNVIEPSFG LGRIMYTVFE HTFHVREGDE QRTFFSFPAV VAPFKCSVLP LSQNQEFMPF VKELSEALTR HGVSHKVDDS SGSIGRRYAR TDEIGVAFGV TIDFDTVNKT PHTATLRDRD SMRQIRAEIS ELPSIVQDLA NGNITWADVE ARYPLFEGQE TGKKETIEE //