ID GARS_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 02-DEC-2020, entry version 213. DE RecName: Full=Glycine--tRNA ligase; DE EC=6.1.1.14 {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:24898252, ECO:0000269|PubMed:28675565}; DE AltName: Full=Diadenosine tetraphosphate synthetase {ECO:0000305|PubMed:19710017}; DE Short=Ap4A synthetase {ECO:0000305|PubMed:19710017}; DE EC=2.7.7.- {ECO:0000269|PubMed:19710017}; DE AltName: Full=Glycyl-tRNA synthetase {ECO:0000303|PubMed:19710017}; DE Short=GlyRS {ECO:0000303|PubMed:19710017}; DE AltName: Full=Glycyl-tRNA synthetase 1 {ECO:0000312|HGNC:HGNC:4162}; GN Name=GARS1 {ECO:0000312|HGNC:HGNC:4162}; Synonyms=GARS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 from RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., 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., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA 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 project: RT 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 IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [8] RP SUBCELLULAR LOCATION, VARIANTS CMT2D GLY-125 AND ARG-294, CHARACTERIZATION RP OF VARIANTS CMT2D GLY-125 AND ARG-294, VARIANTS HMN5A PRO-183; ARG-472 AND RP ARG-580, AND CHARACTERIZATION OF VARIANTS HMN5A PRO-183; ARG-472 AND RP 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 role RT 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., Walther T.C., RA 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., Buerckstuemmer T., RA 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 AND THR-736, VARIANT RP [LARGE SCALE ANALYSIS] ALA-42, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [12] RP SUBCELLULAR LOCATION, VARIANTS CMT2D VAL-111; ASN-200; PHE-265; ARG-294; RP LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652, VARIANT LEU-635, RP CHARACTERIZATION OF VARIANTS CMT2D VAL-111; GLY-125; PRO-183; ASN-200; RP PHE-265; ARG-294; LEU-298; PHE-334; ARG-472; ASN-554; ARG-580 AND ALA-652, RP 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 glycyl-tRNA RT synthetase mutations."; RL Hum. Mutat. 35:1363-1371(2014). RN [13] 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] 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 [16] 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-causing RT mutation in human glycyl-tRNA synthetase."; RL Proc. Natl. Acad. Sci. U.S.A. 104:9976-9981(2007). RN [17] {ECO:0000244|PDB:2ZT5, ECO:0000244|PDB:2ZT6, ECO:0000244|PDB:2ZT7, ECO:0000244|PDB:2ZT8, ECO:0000244|PDB:2ZXF} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 55-739 IN COMPLEXES WITH ATP; RP AP4A; GLYCINE AND SUBSTRATE ANALOGS, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, REACTION MECHANISM, AND SUBUNIT. 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 mechanism and RT role for human glycyl-tRNA synthetase in Ap4A homeostasis."; RL J. Biol. Chem. 284:28968-28976(2009). RN [18] {ECO:0000244|PDB:4KR2, ECO:0000244|PDB:4KR3} RP X-RAY CRYSTALLOGRAPHY (3.23 ANGSTROMS) OF 114-739 OF WILD-TYPE AND VARIANT RP GLY-125 IN COMPLEXES WITH TRNA(GLY); AMP; ATP ANALOG AND GLYCINE, FUNCTION, RP CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF ARG-121; ARG-337; ARG-602; RP TYR-658 AND GLN-729, AND CHARACTERIZATION OF VARIANT GLY-125. RX PubMed=24898252; DOI=10.1074/jbc.m114.557249; RA Qin X., Hao Z., Tian Q., Zhang Z., Zhou C., Xie W.; RT "Cocrystal structures of glycyl-tRNA synthetase in complex with tRNA RT suggest multiple conformational states in glycylation."; RL J. Biol. Chem. 289:20359-20369(2014). RN [19] {ECO:0000244|PDB:4KQE, ECO:0000244|PDB:4QEI} RP X-RAY CRYSTALLOGRAPHY (2.74 ANGSTROMS) OF 55-739 OF VARIANT GLY-125 AND RP DOUBLE MUTANT GLY-125/ARG-211 IN COMPLEX WITH TRNA(GLY) AND AMP, AND RP MUTAGENESIS OF CYS-211 AND 486-LEU--LYS-490. RX PubMed=26797133; DOI=10.1074/jbc.m115.679126; RA Deng X., Qin X., Chen L., Jia Q., Zhang Y., Zhang Z., Lei D., Ren G., RA Zhou Z., Wang Z., Li Q., Xie W.; RT "Large Conformational Changes of Insertion 3 in Human Glycyl-tRNA RT Synthetase (hGlyRS) during Catalysis."; RL J. Biol. Chem. 291:5740-5752(2016). RN [20] {ECO:0000244|PDB:5E6M} RP X-RAY CRYSTALLOGRAPHY (2.93 ANGSTROMS) OF 55-739 IN COMPLEX WITH TRNA(GLY) RP AND GLYCYL-AMP. RX PubMed=27261259; DOI=10.1016/j.jmb.2016.05.018; RA Qin X., Deng X., Chen L., Xie W.; RT "Crystal Structure of the Wild-Type Human GlyRS Bound with tRNA(Gly) in a RT Productive Conformation."; RL J. Mol. Biol. 428:3603-3614(2016). RN [21] RP VARIANTS CMT2D GLY-125 AND ARG-294, VARIANTS HMN5A PRO-183 AND ARG-580, AND RP 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., Middleton L.T., RA Sivakumar K., Ionasescu V., Funalot B., Vance J.M., Goldfarb L.G., RA Fischbeck K.H., Green E.D.; RT "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D RT and distal spinal muscular atrophy type V."; RL Am. J. Hum. Genet. 72:1293-1299(2003). RN [22] RP VARIANT LEU-635, AND VARIANTS CMT2D PHE-334 AND ALA-652. RX PubMed=17101916; DOI=10.1212/01.wnl.0000242619.52335.bc; RA James P.A., Cader M.Z., Muntoni F., Childs A.M., Crow Y.J., Talbot K.; RT "Severe childhood SMA and axonal CMT due to anticodon binding domain RT mutations in the GARS gene."; RL Neurology 67:1710-1712(2006). RN [23] RP VARIANT CMT2D VAL-111. RX PubMed=17663003; DOI=10.1016/j.jns.2007.06.047; RA Rohkamm B., Reilly M.M., Lochmueller H., Schlotter-Weigel B., Barisic N., RA Schoels L., Nicholson G., Pareyson D., Laura M., Janecke A.R., RA Miltenberger-Miltenyi G., John E., Fischer C., Grill F., Wakeling W., RA Davis M., Pieber T.R., Auer-Grumbach M.; RT "Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with RT predominant hand involvement and Silver syndrome."; RL J. Neurol. Sci. 263:100-106(2007). RN [24] RP VARIANT CMT2D LEU-298. RX PubMed=20169446; DOI=10.1007/s00415-010-5491-x; RA Hamaguchi A., Ishida C., Iwasa K., Abe A., Yamada M.; RT "Charcot-Marie-Tooth disease type 2D with a novel glycyl-tRNA synthetase RT gene (GARS) mutation."; RL J. Neurol. 257:1202-1204(2010). RN [25] RP VARIANTS HMN5A ASN-200 AND PHE-265. RX PubMed=23279345; DOI=10.1111/j.1529-8027.2012.00442.x; RA Lee H.J., Park J., Nakhro K., Park J.M., Hur Y.M., Choi B.O., Chung K.W.; RT "Two novel mutations of GARS in Korean families with distal hereditary RT motor neuropathy type V."; RL J. Peripher. Nerv. Syst. 17:418-421(2012). RN [26] 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., Erwa W., RA Trajanoski S., Strom T.M., Auer-Grumbach M.; RT "Whole-exome sequencing in patients with inherited neuropathies: outcome RT and challenges."; RL J. Neurol. 261:970-982(2014). RN [27] RP VARIANT CMT2D PHE-334. RX PubMed=24604904; DOI=10.1136/jnnp-2013-306740; RA Klein C.J., Middha S., Duan X., Wu Y., Litchy W.J., Gu W., Dyck P.J., RA Gavrilova R.H., Smith D.I., Kocher J.P., Dyck P.J.; RT "Application of whole exome sequencing in undiagnosed inherited RT polyneuropathies."; RL J. Neurol. Neurosurg. Psych. 85:1265-1272(2014). RN [28] RP VARIANTS CMT2D TYR-200 AND ARG-292. RX PubMed=26244500; DOI=10.1371/journal.pone.0133423; RA Liao Y.C., Liu Y.T., Tsai P.C., Chang C.C., Huang Y.H., Soong B.W., RA Lee Y.C.; RT "Two novel de novo gars mutations cause early-onset axonal Charcot-Marie- RT tooth disease."; RL PLoS ONE 10:E0133423-E0133423(2015). RN [29] RP CHARACTERIZATION OF VARIANTS CMT2D GLY-125 AND ARG-294, AND RP CHARACTERIZATION OF VARIANT HMN5A PRO-183. RX PubMed=26503042; DOI=10.1038/nature15510; RA He W., Bai G., Zhou H., Wei N., White N.M., Lauer J., Liu H., Shi Y., RA Dumitru C.D., Lettieri K., Shubayev V., Jordanova A., Guergueltcheva V., RA Griffin P.R., Burgess R.W., Pfaff S.L., Yang X.L.; RT "CMT2D neuropathy is linked to the neomorphic binding activity of glycyl- RT tRNA synthetase."; RL Nature 526:710-714(2015). RN [30] RP ERRATUM OF PUBMED:26503042. RX PubMed=26789244; DOI=10.1038/nature16499; RA He W., Bai G., Zhou H., Wei N., White N.M., Lauer J., Liu H., Shi Y., RA Dan Dumitru C., Lettieri K., Shubayev V., Jordanova A., Guergueltcheva V., RA Griffin P.R., Burgess R.W., Pfaff S.L., Yang X.L.; RT "Corrigendum: CMT2D neuropathy is linked to the neomorphic binding activity RT of glycyl-tRNA synthetase."; RL Nature 532:402-402(2016). RN [31] RP VARIANT GLN-310, CHARACTERIZATION OF VARIANT GLN-310, CATALYTIC ACTIVITY, RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=28675565; DOI=10.1002/humu.23287; RA Oprescu S.N., Chepa-Lotrea X., Takase R., Golas G., Markello T.C., RA Adams D.R., Toro C., Gropman A.L., Hou Y.M., Malicdan M.C.V., Gahl W.A., RA Tifft C.J., Antonellis A.; RT "Compound heterozygosity for loss-of-function GARS variants results in a RT multisystem developmental syndrome that includes severe growth RT retardation."; RL Hum. Mutat. 38:1412-1420(2017). RN [32] RP VARIANTS ILE-268 AND CYS-412. RX PubMed=28594869; DOI=10.1371/journal.pone.0178125; RA Nafisinia M., Riley L.G., Gold W.A., Bhattacharya K., Broderick C.R., RA Thorburn D.R., Simons C., Christodoulou J.; RT "Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause RT mitochondrial respiratory chain dysfunction."; RL PLoS ONE 12:E0178125-E0178125(2017). CC -!- FUNCTION: Catalyzes the ATP-dependent ligation of glycine to the 3'-end CC of its cognate tRNA, via the formation of an aminoacyl-adenylate CC intermediate (Gly-AMP) (PubMed:17544401, PubMed:28675565, CC PubMed:24898252). Also produces diadenosine tetraphosphate (Ap4A), a CC universal pleiotropic signaling molecule needed for cell regulation CC pathways, by direct condensation of 2 ATPs. Thereby, may play a special CC role in Ap4A homeostasis (PubMed:19710017). CC {ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:19710017, CC ECO:0000269|PubMed:24898252, ECO:0000269|PubMed:28675565}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + glycine + tRNA(Gly) = AMP + diphosphate + glycyl- CC tRNA(Gly); Xref=Rhea:RHEA:16013, Rhea:RHEA-COMP:9664, Rhea:RHEA- CC COMP:9683, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57305, CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78522, ChEBI:CHEBI:456215; CC EC=6.1.1.14; Evidence={ECO:0000269|PubMed:17544401, CC ECO:0000269|PubMed:24898252, ECO:0000269|PubMed:28675565}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16014; CC Evidence={ECO:0000305|PubMed:24898252}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2 ATP + H(+) = diphosphate + P(1),P(4)-bis(5'-adenosyl) CC tetraphosphate; Xref=Rhea:RHEA:34935, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58141; CC Evidence={ECO:0000269|PubMed:19710017}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34936; CC Evidence={ECO:0000305|PubMed:19710017}; CC -!- ACTIVITY REGULATION: Ap4A synthesis is inhibited by tRNA, via the CC disruption of the second ATP-binding site by direct blocking and/or by CC tRNA-induced conformational change. {ECO:0000269|PubMed:19710017}. 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 KM=0.74 uM for tRNA(Gly) {ECO:0000269|PubMed:28675565}; CC Note=kcat is 0.049 sec(-1) for aminoacylation of tRNA(Gly). CC {ECO:0000269|PubMed:28675565}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17544401, CC ECO:0000269|PubMed:17545306, ECO:0000305|PubMed:19710017, CC ECO:0000305|PubMed:24898252}. CC -!- INTERACTION: CC P41250; P41250: GARS1; NbExp=4; IntAct=EBI-724143, EBI-724143; CC P41250; Q9CZD3: Gars1; Xeno; NbExp=2; IntAct=EBI-724143, EBI-8321941; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17035524}. CC Mitochondrion {ECO:0000250|UniProtKB:Q9CZD3}. Cell projection, axon CC {ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:25168514}. Secreted CC {ECO:0000250|UniProtKB:Q9CZD3}. Secreted, extracellular exosome CC {ECO:0000250|UniProtKB:Q9CZD3}. Note=In transfected COS7 cells, not CC detected in mitochondria, nor in Golgi apparatus (PubMed:17035524). CC Secreted by motor neuron, possibly through the exosome pathway (By CC similarity). {ECO:0000250|UniProtKB:Q9CZD3, CC ECO:0000269|PubMed:17035524}. CC -!- TISSUE SPECIFICITY: Widely expressed, including in 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 the CC peripheral nervous system, characterized by progressive weakness and CC atrophy, initially of the peroneal muscles and later of the distal CC muscles of the arms. Charcot-Marie-Tooth disease is classified in two CC main groups on the basis of electrophysiologic properties and CC histopathology: primary peripheral demyelinating neuropathies CC (designated CMT1 when they are dominantly inherited) and primary CC peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group CC are characterized by signs of axonal degeneration in the absence of CC obvious myelin alterations, normal or slightly reduced nerve conduction CC velocities, and progressive distal muscle weakness and atrophy. CC {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, CC ECO:0000269|PubMed:17101916, ECO:0000269|PubMed:17663003, CC ECO:0000269|PubMed:20169446, ECO:0000269|PubMed:24604904, CC ECO:0000269|PubMed:25168514, ECO:0000269|PubMed:26244500, CC ECO:0000269|PubMed:26503042}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. Contrary to the wild-type CC protein, CMT2D variants Gly-125 and Arg-294 strongly interact with CC NRP1. This interaction may compete out VEGFA binding and inhibits CC VEGFA-NRP1 signling which is essential for motor neuron survival, as CC suggested by experiments done in a mouse model. CC {ECO:0000269|PubMed:26503042}. 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 distal CC motor neuronopathies. These constitute a heterogeneous group of CC neuromuscular diseases caused by selective degeneration of motor CC neurons in the anterior horn of the spinal cord, without sensory CC deficit in the posterior horn. The overall clinical picture consists of CC a classical distal muscular atrophy syndrome in the legs without CC clinical sensory loss. The disease starts with weakness and wasting of CC distal muscles of the anterior tibial and peroneal compartments of the CC legs. Later on, weakness and atrophy may expand to the proximal muscles CC of the lower limbs and/or to the distal upper limbs. CC {ECO:0000269|PubMed:12690580, ECO:0000269|PubMed:17035524, CC ECO:0000269|PubMed:23279345, ECO:0000269|PubMed:24627108, CC ECO:0000269|PubMed:26503042}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. Contrary to the wild-type CC protein, HMN5A variant Pro-183 strongly interacts with NRP1. This CC interaction may compete out VEGFA binding and inhibits VEGFA-NRP1 CC signling which is essential for motor neuron survival, as suggested by CC experiments done in a mouse model. {ECO:0000269|PubMed:26503042}. CC -!- MISCELLANEOUS: Human GlyRS uses direct ATP condensation to synthesize CC Ap4A, a unique amino acid-independent mechanism, in contrast to the CC classical amino acid-dependent mechanism for synthesis of Ap4A by a CC tRNA synthetase, that involves the generation of an enzyme-bound CC aminoacyl-AMP which is then attacked by ATP to form Ap4A. CC {ECO:0000269|PubMed:19710017}. CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family. CC {ECO:0000305}. CC -!- CAUTION: According to a report, variant Leu-635 induces reduced CC activity (PubMed:17544401). According to another report, it does not CC affect function (PubMed:25168514). {ECO:0000269|PubMed:17544401, CC ECO:0000269|PubMed:25168514}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA57001.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA86443.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="https://uantwerpen.vib.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_001303701.1; NM_001316772.1. DR RefSeq; NP_002038.2; NM_002047.3. 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 PDB; 5E6M; X-ray; 2.93 A; A/B=55-739. 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 PDBsum; 5E6M; -. DR SMR; P41250; -. DR BioGRID; 108887; 126. DR DIP; DIP-50471N; -. DR IntAct; P41250; 29. DR MINT; P41250; -. DR STRING; 9606.ENSP00000373918; -. DR ChEMBL; CHEMBL4105815; -. DR DrugBank; DB00145; Glycine. DR MoonProt; P41250; -. DR iPTMnet; P41250; -. DR MetOSite; P41250; -. DR PhosphoSitePlus; P41250; -. DR SwissPalm; P41250; -. DR BioMuta; GARS; -. DR DMDM; 313104283; -. DR EPD; P41250; -. DR jPOST; P41250; -. DR MassIVE; P41250; -. DR MaxQB; P41250; -. DR PaxDb; P41250; -. DR PeptideAtlas; P41250; -. DR PRIDE; P41250; -. DR ProteomicsDB; 55453; -. DR ABCD; P41250; 3 sequenced antibodies. DR Antibodypedia; 6744; 348 antibodies. DR DNASU; 2617; -. DR Ensembl; ENST00000389266; ENSP00000373918; ENSG00000106105. DR GeneID; 2617; -. DR KEGG; hsa:2617; -. DR UCSC; uc003tbm.4; human. DR CTD; 2617; -. DR DisGeNET; 2617; -. DR EuPathDB; HostDB:ENSG00000106105.13; -. DR GeneCards; GARS1; -. DR GeneReviews; GARS; -. DR HGNC; HGNC:4162; GARS1. DR HPA; ENSG00000106105; Low tissue specificity. DR MalaCards; GARS1; -. DR MIM; 600287; gene. DR MIM; 600794; phenotype. DR MIM; 601472; phenotype. DR neXtProt; NX_P41250; -. DR OpenTargets; ENSG00000106105; -. 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; KOG2298; Eukaryota. DR GeneTree; ENSGT00940000153759; -. DR HOGENOM; CLU_015515_1_0_1; -. DR InParanoid; P41250; -. DR OMA; YDYGQNG; -. DR OrthoDB; 1183820at2759; -. DR PhylomeDB; P41250; -. DR TreeFam; TF343504; -. DR BRENDA; 6.1.1.14; 2681. DR PathwayCommons; P41250; -. DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation. DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation. DR SABIO-RK; P41250; -. DR BioGRID-ORCS; 2617; 745 hits in 860 CRISPR screens. DR ChiTaRS; GARS; human. DR EvolutionaryTrace; P41250; -. DR GeneWiki; Glycine%E2%80%94tRNA_ligase; -. DR GenomeRNAi; 2617; -. DR Pharos; P41250; Tbio. DR PRO; PR:P41250; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P41250; protein. DR Bgee; ENSG00000106105; Expressed in secondary oocyte and 249 other tissues. DR ExpressionAtlas; P41250; baseline and differential. DR Genevisible; P41250; HS. DR GO; GO:0030424; C:axon; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; ISS:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0030141; C:secretory granule; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004081; F:bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity; IDA:UniProtKB. DR GO; GO:0004820; F:glycine-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB. DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW. DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0006426; P:glycyl-tRNA aminoacylation; IBA:GO_Central. DR GO; GO:0070150; P:mitochondrial glycyl-tRNA aminoacylation; IBA:GO_Central. DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; IMP:UniProtKB. DR CDD; cd00774; GlyRS-like_core; 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; IPR036621; Anticodon-bd_dom_sf. DR InterPro; IPR027031; Gly-tRNA_synthase/POLG2. DR InterPro; IPR033731; GlyRS-like_core. 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 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; Cytoplasm; Disease mutation; KW Hydrolase; Ligase; Mitochondrion; Neurodegeneration; Neuropathy; KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis; KW Reference proteome; Secreted; Transferase. FT CHAIN 1..739 FT /note="Glycine--tRNA ligase" FT /id="PRO_0000072998" FT DOMAIN 63..119 FT /note="WHEP-TRS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00531" FT NP_BIND 331..333 FT /note="ATP" FT /evidence="ECO:0000244|PDB:2ZT7, FT ECO:0000269|PubMed:19710017, ECO:0000305|PubMed:24898252, FT ECO:0000305|PubMed:27261259" FT NP_BIND 342..343 FT /note="ATP" FT /evidence="ECO:0000244|PDB:2ZT7, FT ECO:0000269|PubMed:19710017" FT NP_BIND 457..458 FT /note="ATP" FT /evidence="ECO:0000244|PDB:2ZT7, FT ECO:0000269|PubMed:19710017, ECO:0000305|PubMed:24898252, FT ECO:0000305|PubMed:27261259" FT REGION 576..578 FT /note="Glycine binding" FT /evidence="ECO:0000244|PDB:2ZT7, ECO:0000244|PDB:4KR3, FT ECO:0000269|PubMed:19710017, ECO:0000269|PubMed:24898252" FT BINDING 299 FT /note="Glycine" FT /evidence="ECO:0000244|PDB:2ZT7, ECO:0000244|PDB:4KR3, FT ECO:0000269|PubMed:19710017, ECO:0000269|PubMed:24898252, FT ECO:0000305|PubMed:27261259" FT BINDING 350 FT /note="Glycine" FT /evidence="ECO:0000244|PDB:2ZT7, ECO:0000244|PDB:4KR3, FT ECO:0000269|PubMed:19710017, ECO:0000269|PubMed:24898252, FT ECO:0000305|PubMed:27261259" FT BINDING 583 FT /note="ATP" FT /evidence="ECO:0000244|PDB:2ZT7, FT ECO:0000269|PubMed:19710017" FT MOD_RES 35 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:23186163" FT MOD_RES 204 FT /note="N6-acetyllysine" FT /evidence="ECO:0000244|PubMed:19608861" FT MOD_RES 453 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9CZD3" FT MOD_RES 501 FT /note="N6-acetyllysine" FT /evidence="ECO:0000244|PubMed:19608861" FT MOD_RES 700 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9CZD3" FT MOD_RES 736 FT /note="Phosphothreonine" FT /evidence="ECO:0000244|PubMed:23186163" FT VARIANT 42 FT /note="P -> A (in dbSNP:rs1049402)" FT /evidence="ECO:0000244|PubMed:23186163, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7753621, ECO:0000269|PubMed:7961834, FT ECO:0000269|PubMed:7962006" FT /id="VAR_054865" FT VARIANT 111 FT /note="A -> V (in CMT2D; shows a reduction in FT aminoacylation activity; dbSNP:rs370531212)" FT /evidence="ECO:0000269|PubMed:17663003, FT ECO:0000269|PubMed:25168514" FT /id="VAR_073187" FT VARIANT 125 FT /note="E -> G (in CMT2D; phenotype overlapping with DSMA-V; FT complements the defect of the wild-type gene in yeast; FT contrary to the wild-type protein, strongly binds to NRP1 FT and competes with VEGFA for NRP1-binding; displays slightly FT elevated aminoacylation activity over wild-type; FT dbSNP:rs137852645)" FT /evidence="ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:24898252, FT ECO:0000269|PubMed:25168514, ECO:0000269|PubMed:26503042" FT /id="VAR_018718" FT VARIANT 183 FT /note="L -> P (in HMN5A; does not complement the defect of FT the wild-type gene in yeast; contrary to the wild-type FT protein, strongly interacts with NRP1; dbSNP:rs137852644)" FT /evidence="ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:25168514, FT ECO:0000269|PubMed:26503042" FT /id="VAR_018719" FT VARIANT 200 FT /note="D -> N (in CMT2D and HMN5A; shows a large reduction FT in aminoacylation activity; dbSNP:rs1554337369)" FT /evidence="ECO:0000269|PubMed:23279345, FT ECO:0000269|PubMed:25168514" FT /id="VAR_073188" FT VARIANT 200 FT /note="D -> Y (in CMT2D)" FT /evidence="ECO:0000269|PubMed:26244500" FT /id="VAR_074016" FT VARIANT 265 FT /note="S -> F (in CMT2D and HMN5A; shows a large reduction FT in aminoacylation activity; demonstrates a change in the FT subcellular location pattern; does not associate with FT granules; dbSNP:rs1554337974)" FT /evidence="ECO:0000269|PubMed:23279345, FT ECO:0000269|PubMed:25168514" FT /id="VAR_073189" FT VARIANT 268 FT /note="T -> I (found in a patient with mild left FT ventricular posterior wall hypertrophy, exercise FT intolerance and lactic acidosis; unknown pathological FT significance; dbSNP:rs2230310)" FT /evidence="ECO:0000269|PubMed:28594869" FT /id="VAR_054866" FT VARIANT 292 FT /note="M -> R (in CMT2D; dbSNP:rs1064795123)" FT /evidence="ECO:0000269|PubMed:26244500" FT /id="VAR_074017" FT VARIANT 294 FT /note="G -> R (in CMT2D; shows a large reduction in FT aminoacylation activity; does not impair transcription or FT translation or protein stability; contrary to the wild-type FT protein, strongly interacts with NRP1; dbSNP:rs137852643)" FT /evidence="ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:25168514, FT ECO:0000269|PubMed:26503042" FT /id="VAR_018720" FT VARIANT 298 FT /note="P -> L (in CMT2D; shows a large reduction in FT aminoacylation activity; demonstrates a change in FT subcellular location pattern; does not associate with FT granules; dbSNP:rs137852648)" FT /evidence="ECO:0000269|PubMed:20169446, FT ECO:0000269|PubMed:25168514" FT /id="VAR_073190" FT VARIANT 310 FT /note="R -> Q (probable disease-associated variant found in FT a patient with growth retardation, microcephaly, thinning FT of the corpus callosum, decreased white matter and brain FT stem involvement, as well as large calvaria, cerebellar FT vermis atrophy, dysmorphic features, prominent epicanthal FT folds, hypotelorism, high-arched palate, delayed motor FT milestones, apnea and sparse thin scalp hair; reduces to FT less than 1% aminoacylation activity; dbSNP:rs1135401748)" FT /evidence="ECO:0000269|PubMed:28675565" FT /id="VAR_079827" FT VARIANT 334 FT /note="I -> F (in CMT2D; shows a large reduction in FT aminoacylation activity; demonstrates a change in FT subcellular location pattern; does not associate with FT granules; unknown pathological significance; FT dbSNP:rs1554338260)" FT /evidence="ECO:0000269|PubMed:17101916, FT ECO:0000269|PubMed:24604904, ECO:0000269|PubMed:25168514" FT /id="VAR_073191" FT VARIANT 388 FT /note="R -> Q (in dbSNP:rs17159287)" FT /id="VAR_054867" FT VARIANT 412 FT /note="R -> C (found in a patient with mild left FT ventricular posterior wall hypertrophy, exercise FT intolerance and lactic acidosis; unknown pathological FT significance; dbSNP:rs770924455)" FT /evidence="ECO:0000269|PubMed:28594869" FT /id="VAR_079828" FT VARIANT 472 FT /note="H -> R (in HMN5A; shows a large reduction in FT aminoacylation activity; does not complement the defect of FT the wild-type gene in yeast; dbSNP:rs1060502838)" FT /evidence="ECO:0000269|PubMed:17035524, FT ECO:0000269|PubMed:24627108, ECO:0000269|PubMed:25168514" FT /id="VAR_073192" FT VARIANT 554 FT /note="D -> N (in CMT2D; demonstrates no change in FT subcellular location pattern; dbSNP:rs137852647)" FT /evidence="ECO:0000269|PubMed:25168514" FT /id="VAR_073193" FT VARIANT 580 FT /note="G -> R (in HMN5A; higher dimerization stability; FT loss of activity; shows a large reduction in aminoacylation FT activity; dbSNP:rs137852646)" FT /evidence="ECO:0000269|PubMed:12690580, FT ECO:0000269|PubMed:17035524, ECO:0000269|PubMed:17545306, FT ECO:0000269|PubMed:25168514" FT /id="VAR_018721" FT VARIANT 598 FT /note="G -> A (in HMN5A; unknown pathological significance; FT dbSNP:rs766280100)" FT /evidence="ECO:0000269|PubMed:17101916" FT /id="VAR_079829" FT VARIANT 635 FT /note="S -> L (polymorphism; has no effect on subcellular FT localization; results in reduced activity; FT dbSNP:rs201358272)" FT /evidence="ECO:0000269|PubMed:17101916, FT ECO:0000269|PubMed:17544401, ECO:0000269|PubMed:25168514" FT /id="VAR_073194" FT VARIANT 652 FT /note="G -> A (in CMT2D; shows a large reduction in FT aminoacylation activity; demonstrates a change in FT subcellular location pattern; does not associate with FT granules; dbSNP:rs747080824)" FT /evidence="ECO:0000269|PubMed:17101916, FT ECO:0000269|PubMed:25168514" FT /id="VAR_073195" FT MUTAGEN 121 FT /note="R->A: Decrease in catalytic activity by about 10- FT fold." FT /evidence="ECO:0000269|PubMed:24898252" FT MUTAGEN 211 FT /note="C->R: Displays 62% of wild-type catalytic activity. FT Displays 20% of wild-type catalytic activity; when FT associated with G-125." FT /evidence="ECO:0000269|PubMed:26797133" FT MUTAGEN 337 FT /note="R->A: Decrease in catalytic activity by more than FT 10-fold." FT /evidence="ECO:0000269|PubMed:24898252" FT MUTAGEN 486..490 FT /note="Missing: Loss of catalytic activity." FT /evidence="ECO:0000269|PubMed:26797133" FT MUTAGEN 602 FT /note="R->A: Decrease in catalytic activity by more than FT 10-fold." FT /evidence="ECO:0000269|PubMed:24898252" FT MUTAGEN 658 FT /note="Y->F: Decrease in catalytic activity by more than FT 10-fold." FT /evidence="ECO:0000269|PubMed:24898252" FT MUTAGEN 729 FT /note="Q->A,N: Decrease in catalytic activity by about 10- FT fold." FT /evidence="ECO:0000269|PubMed:24898252" FT CONFLICT 9..18 FT /note="Missing (in Ref. 3; BAG58412)" FT /evidence="ECO:0000305" FT CONFLICT 205 FT /note="D -> G (in Ref. 3; BAG51964)" FT /evidence="ECO:0000305" FT CONFLICT 530 FT /note="M -> I (in Ref. 2; AAA86443)" FT /evidence="ECO:0000305" FT CONFLICT 634 FT /note="L -> S (in Ref. 3; BAG51964)" FT /evidence="ECO:0000305" FT TURN 62..64 FT /evidence="ECO:0000244|PDB:5E6M" FT HELIX 65..80 FT /evidence="ECO:0000244|PDB:5E6M" FT TURN 81..83 FT /evidence="ECO:0000244|PDB:5E6M" FT HELIX 95..112 FT /evidence="ECO:0000244|PDB:5E6M" FT HELIX 121..130 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 133..136 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 139..141 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 148..150 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 152..168 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 170..173 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 182..185 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 186..191 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 194..197 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 199..208 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 211..213 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 214..227 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 229..231 FT /evidence="ECO:0000244|PDB:2Q5I" FT HELIX 233..243 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 244..248 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 251..260 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 266..268 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 276..279 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 283..285 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 287..296 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 298..300 FT /evidence="ECO:0000244|PDB:2ZXF" FT HELIX 301..305 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 308..314 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 315..317 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 321..330 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 339..341 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 344..355 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 357..359 FT /evidence="ECO:0000244|PDB:4KQE" FT HELIX 365..367 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 368..370 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 372..376 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 378..382 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 388..391 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 392..397 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 400..402 FT /evidence="ECO:0000244|PDB:2PME" FT HELIX 404..420 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 424..426 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 427..431 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 434..436 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 442..451 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 454..462 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 467..476 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 482..484 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 501..507 FT /evidence="ECO:0000244|PDB:4KQE" FT HELIX 512..519 FT /evidence="ECO:0000244|PDB:4KQE" FT HELIX 524..535 FT /evidence="ECO:0000244|PDB:4KQE" FT STRAND 541..544 FT /evidence="ECO:0000244|PDB:4KQE" FT STRAND 547..550 FT /evidence="ECO:0000244|PDB:4KQE" FT STRAND 552..554 FT /evidence="ECO:0000244|PDB:4KQE" FT STRAND 562..564 FT /evidence="ECO:0000244|PDB:2PMF" FT TURN 565..567 FT /evidence="ECO:0000244|PDB:2PMF" FT STRAND 568..570 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 573..580 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 581..592 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 593..595 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 597..600 FT /evidence="ECO:0000244|PDB:4KQE" FT STRAND 603..605 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 609..611 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 615..621 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 625..627 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 628..640 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 645..647 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 650..652 FT /evidence="ECO:0000244|PDB:5E6M" FT HELIX 654..663 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 668..672 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 674..677 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 679..681 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 683..688 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 689..691 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 694..698 FT /evidence="ECO:0000244|PDB:2ZT5" FT TURN 699..701 FT /evidence="ECO:0000244|PDB:2ZT5" FT HELIX 702..710 FT /evidence="ECO:0000244|PDB:2ZT5" FT STRAND 712..714 FT /evidence="ECO:0000244|PDB:4KR3" FT HELIX 716..722 FT /evidence="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 //