Glycine—tRNA ligase

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GARS
Protein GARS PDB 2pme.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases GARS, CMT2D, DSMAV, GlyRS, HMN5, SMAD1, glycyl-tRNA synthetase
External IDs OMIM: 600287 MGI: 2449057 HomoloGene: 1547 GeneCards: 2617
RNA expression pattern
PBB GE GARS 208693 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002047
NM_001316772

NM_180678

RefSeq (protein)

NP_002038.2
NP_001303701.1

NP_851009.2

Location (UCSC) Chr 7: 30.59 – 30.63 Mb Chr 6: 55.04 – 55.08 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Glycine—tRNA ligase also known as glycyl-tRNA synthetase is an enzyme that in humans is encoded by the GARS gene.[3][4][5]

Function[edit]

This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases.[5]

Reaction[edit]

glycine-tRNA ligase
Identifiers
EC number 6.1.1.14
CAS number 9037-62-1
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

In enzymology, a glycine-tRNA ligase (EC 6.1.1.14) is an enzyme that catalyzes the chemical reaction

ATP + glycine + tRNAGly AMP + diphosphate + glycyl-tRNAGly

The 3 substrates of this enzyme are ATP, glycine, and tRNA(Gly), whereas its 3 products are AMP, diphosphate, and glycyl-tRNA(Gly).

This enzyme belongs to the family of ligases, to be specific those forming carbon-oxygen bonds in aminoacyl-tRNA and related compounds. The systematic name of this enzyme class is glycine:tRNAGly ligase (AMP-forming). Other names in common use include glycyl-tRNA synthetase, glycyl-transfer ribonucleate synthetase, glycyl-transfer RNA synthetase, glycyl-transfer ribonucleic acid synthetase, and glycyl translase. This enzyme participates in glycine, serine and threonine metabolism and aminoacyl-trna biosynthesis.

Interactions[edit]

Glycyl-tRNA synthetase has been shown to interact with EEF1D.[6]

Clinical relevance[edit]

Glycyl-tRNA synthetase has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis.[5]

The peripheral neuropathy Charcot-Marie-Tooth disease type 2D (CMT2D) has been liked to dominant mutations in GARS.[7] CMT2D usually manifests during the teenage years, and results in muscle weakness predominantly in the hands and feet.[8] Two mouse models of CMT2D have been used to better understand the disease, identifying that the disorder is caused by a toxic gain of function of the mutant glycine-tRNA ligase protein.[9] The CMT2D mice display peripheral nerve axon degeneration [10][11] and defective development of the neuromuscular junction.[12]

See also[edit]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Nichols RC, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Nov 1995). "Localization of two human autoantigen genes by PCR screening and in situ hybridization--glycyl-tRNA synthetase locates to 7p15 and alanyl-tRNA synthetase locates to 16q22". Genomics. 30 (1): 131–2. doi:10.1006/geno.1995.0028. PMID 8595897. 
  4. ^ Ionasescu V, Searby C, Sheffield VC, Roklina T, Nishimura D, Ionasescu R (Sep 1996). "Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)". Human Molecular Genetics. 5 (9): 1373–5. doi:10.1093/hmg/5.9.1373. PMID 8872480. 
  5. ^ a b c "Entrez Gene: GARS glycyl-tRNA synthetase". 
  6. ^ Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (Feb 2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochemical and Biophysical Research Communications. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477. 
  7. ^ Motley WW, Talbot K, Fischbeck KH (Feb 2010). "GARS axonopathy: not every neuron's cup of tRNA". Trends in Neurosciences. 33 (2): 59–66. doi:10.1016/j.tins.2009.11.001. PMC 2822721free to read. PMID 20152552. 
  8. ^ Sivakumar K, Kyriakides T, Puls I, Nicholson GA, Funalot B, Antonellis A, Sambuughin N, Christodoulou K, Beggs JL, Zamba-Papanicolaou E, Ionasescu V, Dalakas MC, Green ED, Fischbeck KH, Goldfarb LG (Oct 2005). "Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations". Brain. 128 (Pt 10): 2304–14. doi:10.1093/brain/awh590. PMID 16014653. 
  9. ^ Motley WW, Seburn KL, Nawaz MH, Miers KE, Cheng J, Antonellis A, Green ED, Talbot K, Yang XL, Fischbeck KH, Burgess RW (Dec 2011). "Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels". PLoS Genetics. 7 (12): e1002399. doi:10.1371/journal.pgen.1002399. PMC 3228828free to read. PMID 22144914. 
  10. ^ Seburn KL, Nangle LA, Cox GA, Schimmel P, Burgess RW (Sep 2006). "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model". Neuron. 51 (6): 715–26. doi:10.1016/j.neuron.2006.08.027. PMID 16982418. 
  11. ^ Achilli F, Bros-Facer V, Williams HP, Banks GT, AlQatari M, Chia R, Tucci V, Groves M, Nickols CD, Seburn KL, Kendall R, Cader MZ, Talbot K, van Minnen J, Burgess RW, Brandner S, Martin JE, Koltzenburg M, Greensmith L, Nolan PM, Fisher EM (Jul–Aug 2009). "An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy". Disease Models & Mechanisms. 2 (7-8): 359–73. doi:10.1242/dmm.002527. PMC 2707104free to read. PMID 19470612. 
  12. ^ Sleigh JN, Grice SJ, Burgess RW, Talbot K, Cader MZ (May 2014). "Neuromuscular junction maturation defects precede impaired lower motor neuron connectivity in Charcot-Marie-Tooth type 2D mice". Human Molecular Genetics. 23 (10): 2639–50. doi:10.1093/hmg/ddt659. PMID 24368416. 

Further reading[edit]

External links[edit]