ID SYG_HUMAN Reviewed; 739 AA. AC P41250; Q969Y1; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 27-MAY-2002, sequence version 2. DT 04-NOV-2008, entry version 86. DE RecName: Full=Glycyl-tRNA synthetase; DE EC=6.1.1.14; DE AltName: Full=Glycine--tRNA ligase; 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]. RX MEDLINE=95050870; 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]. RX MEDLINE=95273165; 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]. 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 [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-739. RX MEDLINE=95050687; 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 [5] RP NUCLEOTIDE SEQUENCE OF 348-739. RA Andrews S., Langston Y., Stoneking T., Maupin R.; RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP VARIANTS CMT2D GLY-125 AND ARG-294, VARIANTS DSMA-V 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). CC -!- CATALYTIC ACTIVITY: ATP + glycine + tRNA(Gly) = AMP + diphosphate CC + glycyl-tRNA(Gly). CC -!- SUBUNIT: Homodimer. CC -!- TISSUE SPECIFICITY: Widely expressed, including brain and spinal CC cord. CC -!- DISEASE: Defects in GARS are the cause of Charcot-Marie-Tooth CC disease type 2D (CMT2D) [MIM:601472]. CMT2D is a form of Charcot- CC Marie-Tooth disease, the most common inherited disorder of the CC peripheral nervous system. Charcot-Marie-Tooth disease is CC classified in two main groups on the basis of electrophysiologic CC properties and histopathology: primary peripheral demyelinating CC neuropathy or CMT1, and primary peripheral axonal neuropathy or CC CMT2. Neuropathies of the CMT2 group are characterized by signs of CC axonal regeneration in the absence of obvious myelin alterations, CC normal or slightly reduced nerve conduction velocities, and CC progressive distal muscle weakness and atrophy. CMT2D is CC characterized by a more severe phenotype in the upper extremities CC (severe weakness and atrophy, absence of tendon reflexes) than in CC the lower limbs. CMT2D inheritance is autosomal dominant. CC -!- DISEASE: Defects in GARS are the cause of distal spinal muscular CC atrophy type V (DSMA-V) [MIM:600794]. DSMA-V is an autosomal CC dominant distal hereditary motor neuropathy (dHMN) with a CC phenotype similar to CMTD2. The main characteristic that CC distinguishes these disorders is the less severe distal sensory CC involvement in DSMA-V patients. CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase CC family. CC -!- SIMILARITY: Contains 1 WHEP-TRS domain. CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db; CC URL="http://www.molgen.ua.ac.be/CMTMutations/"; CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=GARS"; 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; BC007722; AAH07722.1; -; mRNA. DR EMBL; BC007755; AAH07755.1; -; mRNA. DR EMBL; U09587; AAA57001.1; ALT_INIT; mRNA. DR EMBL; AC004976; AAC71652.1; -; Genomic_DNA. DR PIR; A55314; A55314. DR RefSeq; NP_002038.2; -. 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 PDBsum; 2PME; -. DR PDBsum; 2PMF; -. DR PDBsum; 2Q5H; -. DR PDBsum; 2Q5I; -. DR IntAct; P41250; -. DR Ensembl; ENSG00000106105; Homo sapiens. DR GeneID; 2617; -. DR KEGG; hsa:2617; -. DR HGNC; HGNC:4162; GARS. DR HPA; HPA017896; -. DR MIM; 600287; gene. DR MIM; 600794; phenotype. DR MIM; 601472; phenotype. DR Orphanet; 64746; Charcot-Marie-Tooth disease, type 2, autosomal dominant. DR Orphanet; 99938; Charcot-Marie-Tooth disease, type 2D, autosomal dominant. DR Orphanet; 139536; Neuropathy, motor, distal, hereditary , type 5. DR PharmGKB; PA28575; -. DR HOGENOM; P41250; -. DR HOVERGEN; P41250; -. DR DrugBank; DB00145; Glycine. DR NextBio; 10303; -. DR ArrayExpress; P41250; -. DR CleanEx; HS_GARS; -. DR GermOnline; ENSG00000106105; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005625; C:soluble fraction; TAS:ProtInc. DR GO; GO:0004820; F:glycine-tRNA ligase activity; TAS:ProtInc. DR InterPro; IPR002314; aa-tRNA-synt_IIb. DR InterPro; IPR006195; aa-tRNA-synth_II. DR InterPro; IPR004154; Anticodon_bd. DR InterPro; IPR002315; tRNA-synt_gly. DR InterPro; IPR000738; WHEP-TRS. DR Gene3D; G3DSA:3.40.50.800; Anticodon_bd; 1. DR PANTHER; PTHR10745; tRNA-synt_gly; 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 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; Aminoacyl-tRNA synthetase; ATP-binding; KW Charcot-Marie-Tooth disease; Disease mutation; Ligase; KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis. FT CHAIN 1 739 Glycyl-tRNA synthetase. FT /FTId=PRO_0000072998. FT DOMAIN 63 119 WHEP-TRS. FT MOD_RES 453 453 Phosphotyrosine (By similarity). FT VARIANT 125 125 E -> G (in CMT2D; phenotype overlapping FT with DSMA-V). FT /FTId=VAR_018718. FT VARIANT 183 183 L -> P (in DSMA-V). FT /FTId=VAR_018719. FT VARIANT 294 294 G -> R (in CMT2D). FT /FTId=VAR_018720. FT VARIANT 580 580 G -> R (in DSMA-V). FT /FTId=VAR_018721. FT CONFLICT 530 530 M -> I (in Ref. 2; AAA86443). FT HELIX 121 130 FT STRAND 133 136 FT HELIX 139 141 FT STRAND 148 150 FT HELIX 152 173 FT STRAND 182 185 FT HELIX 186 192 FT STRAND 195 205 FT TURN 206 208 FT STRAND 209 213 FT HELIX 214 226 FT HELIX 233 243 FT HELIX 244 248 FT HELIX 251 260 FT STRAND 266 268 FT STRAND 276 279 FT STRAND 283 285 FT STRAND 287 291 FT STRAND 293 296 FT HELIX 301 306 FT HELIX 308 314 FT TURN 315 317 FT STRAND 321 330 FT STRAND 344 355 FT HELIX 357 359 FT HELIX 365 367 FT TURN 368 370 FT STRAND 372 376 FT HELIX 378 383 FT STRAND 388 391 FT HELIX 392 397 FT STRAND 400 402 FT HELIX 404 420 FT HELIX 424 426 FT STRAND 427 431 FT STRAND 443 451 FT STRAND 454 466 FT HELIX 469 472 FT STRAND 573 580 FT HELIX 581 592 FT STRAND 593 595 FT STRAND 603 605 FT TURN 609 611 FT STRAND 615 621 FT HELIX 625 627 FT HELIX 628 640 FT STRAND 645 647 FT HELIX 654 663 FT STRAND 668 672 FT HELIX 674 677 FT STRAND 678 681 FT STRAND 683 688 FT TURN 689 691 FT STRAND 694 698 FT TURN 699 701 FT HELIX 702 710 FT HELIX 716 722 SQ SEQUENCE 739 AA; 83140 MW; 55DDD57119F438E5 CRC64; MPSPRPVLLR GARAALLLLL PPRLLARPSL LLRRSLSAAS CAPISLPAAA 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 //