Protein Information

General Information
MoonProt ID354
First appeared in release2.0
Name(s)glycyl tRNA synthetase, ****NEOMORPHIC MOONLIGHTING PROTEIN***, Glycine--tRNA ligase, Gene: Gars
UniProt IDQ9CZD3 (SYG_MOUSE
GO termsGO:0006412 translation GO:0006418 tRNA aminoacylation for protein translation GO:0006426 glycyl-tRNA aminoacylation GO:0015966 diadenosine tetraphosphate biosynthetic process GO:0000166 nucleotide binding GO:0004081 bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity GO:0004812 aminoacyl-tRNA ligase activity GO:0004820 glycine-tRNA ligase activity GO:0005515 protein binding GO:0005524 ATP binding GO:0016787 hydrolase activity GO:0016874 ligase activity GO:0046983 protein dimerization activity GO:0005654 nucleoplasm GO:0005737 cytoplasm GO:0005739 mitochondrion GO:0030141 secretory granule GO:0030424 axon GO:0042995 cell projection GO:0070062 extracellular exosome GO:0005515 protein binding
Organisms for which functions have been demonstratedMus musculus (mouse)
Sequence length729 amino acids
FASTA sequence>sp|Q9CZD3|SYG_MOUSE Glycine--tRNA ligase OS=Mus musculus GN=Gars PE=1 SV=1 MPCLLPSLLRATRAALPLLSPPRVVAASASQRLLSAPAQPAASRSSMDSAEELLAPLRLAVRQQGDFVRKLKEDKAPQVDVDRAVAELKARKRVLEAKELALQPKDDIVDRAKMEDTLKRRFFYDQAFAIYGGVSGLYDFGPVGCALKNNIIQAWRQHFIQEEQILEIDCTMLTPEPVLKTSGHVDKFADFMVKDVKNGECFRADHLLKAHLQKLMSDKKCSAEKKSEMESVLAQLDNYGQQELADLFVNYNVKSPTTGNDLSPPVPFNLMFQTFIGPGGNMPGYLRPETAQGIFLNFKRLLEFNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHFVDPTEKDHPKFQSVADLCLYLYSAKAQVTGQSARKMRLGDAVEQGVINNSVLGYFIGRIYLYLTKVGISPDKLRFRQHMENEMAHYACDCWDAESKTSYGWIEIVGCADRSCYDLSCHARATKVPLVAEKPLKEPKTVNVVQFEPNKGAVGKAYKKDAKLVLEYLSACDECYISEMELLLSEKGEFTIETEGKTFQLTKDMVSVKRFQKTLHVEEVVPSVIEPSFGLGRIMYTILEHTFHVREGDEQRTFFSFPAVVAPFKCSVLPLSQNQEFMPFVKELSEALTRNGVSHKVDDSSGSIGRRYARTDEIGVAFGITIDFDTVNKTPHTATLRDRDSMRQIRAEVSELPNVVRDLANGNITWADVEARYPLFEGQETGKKETVEE
Structure Information
PDB ID
Quaternary structureDimer
Function 1
Function descriptionglycyl tRNA synthetase, catalyzes attachment of glycine to its cognate tRNA, ATP + glycine + tRNA(Gly) => AMP + diphosphate + glycyl-tRNA(Gly) AND P1,P(4)-bis(5'-guanosyl) tetraphosphate + H2O => GTP + GMP
References for functionSeburn, Kevin L., et al. "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model." Neuron 51.6 (2006): 715-726.
E.C. number3.6.1.17 AND 6.1.1.14 two steps
Location of functional site(s)binding site: 203, 289, 425; nucleotide binding: 321-323, 331-336, 447-448, 570-573
Cellular location of functioncytoplasm
Comments
Function 2
Function description****NEOMORPHIC MOONLIGHTING PROTEIN***, mutant forms have protein binding activity, bind to neuropilin 1 (Nrp1) recpeptor, directly antagonizes binding of the ligand VEGF (vascular endothelial growth factor) to Nrp1, which is an essential signaling pathway in survival of motor neuron
References for functionHe W, Bai G, Zhou H, Wei N, White NM, Lauer J, Liu H, Shi Y, Dumitru CD, Lettieri K, Shubayev V, Jordanova A, Guergueltcheva V, Griffin PR, Burgess RW, Pfaff SL, Yang XL. CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature. 2015 Oct 29;526(7575):710-4. doi: 10.1038/nature15510. PMID: 26503042
E.C. number
Location of functional site(s)
Cellular location of function
Commentsmutations result in Charcot-Marie-Tooth disease (CMT type 2D, CMT2D), peripheral neuropathy, weakness and atrophy in hands and feet