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 26-FEB-2008, entry version 79. DE Glycyl-tRNA synthetase (EC 6.1.1.14) (Glycine--tRNA ligase) (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 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 PhosphoSite; P41250; -. DR Ensembl; ENSG00000106105; Homo sapiens. DR KEGG; hsa:2617; -. DR HGNC; HGNC:4162; GARS. DR MIM; 600287; gene. DR MIM; 600794; phenotype. DR MIM; 601472; phenotype. DR Orphanet; 64746; Charcot-Marie-Tooth disease, type 2. DR PharmGKB; PA28575; -. 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). 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 //