Q9CZD3 · GARS_MOUSE

  • Protein
    Glycine--tRNA ligase
  • Gene
    Gars1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis.

Catalytic activity

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site289glycine (UniProtKB | ChEBI)
Binding site321-323ATP (UniProtKB | ChEBI)
Binding site332-333ATP (UniProtKB | ChEBI)
Binding site340glycine (UniProtKB | ChEBI)
Binding site447-448ATP (UniProtKB | ChEBI)
Binding site566-568glycine (UniProtKB | ChEBI)
Binding site573ATP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentaxon
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentextracellular exosome
Cellular Componentmitochondrion
Cellular Componentsecretory granule
Molecular FunctionATP binding
Molecular FunctionATP:ATP adenylyltransferase activity
Molecular Functionbis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity
Molecular Functionglycine-tRNA ligase activity
Molecular Functionidentical protein binding
Molecular Functionprotein dimerization activity
Biological Processdiadenosine tetraphosphate biosynthetic process
Biological Processglycyl-tRNA aminoacylation
Biological Processmitochondrial glycyl-tRNA aminoacylation
Biological ProcesstRNA aminoacylation for protein translation

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Glycine--tRNA ligase
  • EC number
  • Alternative names
    • Diadenosine tetraphosphate synthetase (Ap4A synthetase) (EC:2.7.7.-
      ) . EC:2.7.7.- (UniProtKB | ENZYME | Rhea)
    • Glycyl-tRNA synthetase 1
      (GlyRS)

Gene names

    • Name
      Gars1
    • Synonyms
      Gars

Organism names

  • Taxonomic identifier
  • Strains
    • BALB/cJ
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9CZD3
  • Secondary accessions
    • Q3TMM4
    • Q3UK01
    • Q8VC67

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Mitochondrion
Cell projection, axon
Secreted
Note: Associated with granules in cultured neuron cells (By similarity).
Secreted by motor neuron and differentiated myotube cell lines, but not by undifferentiated myoblasts, possibly through the exosome pathway (PubMed:26503042).

Keywords

Phenotypes & Variants

Involvement in disease

  • Mice (Nmf249) heterozygous for the P278YK variant are used a model for human Charcot-Marie-Tooth 2D (CMT2D), which is caused by dominant GARS mutations. They exhibit reduced amplitudes of muscle compound action potentials and a large reduction in sciatic nerve conduction velocity in the absence of demyelination or remyelination, resulting from an age-related decrease in the number of large myelinated motor and sensory axons. The loss of myelinated axons is length-dependent, and there is a length- and time-dependent decrease in motor innervation of distal versus proximal muscles. Most of the axonal loss occurs by 1 month of age and mice that survive this period can be long-lived. At the molecular level, the P278YK mutation creates a neomorphic binding activity leading to the interaction of the variant with NRP1. This interaction competes out VEGFA binding and inhibits VEGFA-NRP1 signling which is essential for motor neuron survival. VEGFA, but not GDNF treatment significantly ameliorates the loss of motor function in mutant mice

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variant278found in Nmf249 mice, a Charcot-Marie-Tooth 2D model; involved in neuromuscular dysfunction; contrary to the wild-type protein, strongly interacts with NRP1 and competes with VEGFA for NRP1-binding; no effect on subcellular location

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 41 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

PTM/Processing

Features

Showing features for transit peptide, chain, modified residue.

TypeIDPosition(s)Description
Transit peptide1-33Mitochondrion
ChainPRO_000007299934-729Glycine--tRNA ligase
Modified residue194N6-acetyllysine
Modified residue443Phosphotyrosine
Modified residue491N6-acetyllysine
Modified residue690Phosphoserine
Modified residue726Phosphothreonine

Keywords

Proteomic databases

2D gel databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Homodimer.

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
XENO Q9CZD3GARS1 P412502EBI-8321941, EBI-724143

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain53-109WHEP-TRS

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    729
  • Mass (Da)
    81,878
  • Last updated
    2001-06-01 v1
  • Checksum
    596613F746B9C7D0
MPCLLPSLLRATRAALPLLSPPRVVAASASQRLLSAPAQPAASRSSMDSAEELLAPLRLAVRQQGDFVRKLKEDKAPQVDVDRAVAELKARKRVLEAKELALQPKDDIVDRAKMEDTLKRRFFYDQAFAIYGGVSGLYDFGPVGCALKNNIIQAWRQHFIQEEQILEIDCTMLTPEPVLKTSGHVDKFADFMVKDVKNGECFRADHLLKAHLQKLMSDKKCSAEKKSEMESVLAQLDNYGQQELADLFVNYNVKSPTTGNDLSPPVPFNLMFQTFIGPGGNMPGYLRPETAQGIFLNFKRLLEFNQGKLPFAAAQIGNSFRNEISPRSGLIRVREFTMAEIEHFVDPTEKDHPKFQSVADLCLYLYSAKAQVTGQSARKMRLGDAVEQGVINNSVLGYFIGRIYLYLTKVGISPDKLRFRQHMENEMAHYACDCWDAESKTSYGWIEIVGCADRSCYDLSCHARATKVPLVAEKPLKEPKTVNVVQFEPNKGAVGKAYKKDAKLVLEYLSACDECYISEMELLLSEKGEFTIETEGKTFQLTKDMVSVKRFQKTLHVEEVVPSVIEPSFGLGRIMYTILEHTFHVREGDEQRTFFSFPAVVAPFKCSVLPLSQNQEFMPFVKELSEALTRNGVSHKVDDSSGSIGRRYARTDEIGVAFGITIDFDTVNKTPHTATLRDRDSMRQIRAEVSELPNVVRDLANGNITWADVEARYPLFEGQETGKKETVEE

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict5in Ref. 1; BAE38417
Sequence conflict584in Ref. 1; BAE27003
Sequence conflict597in Ref. 1; BAE27003
Sequence conflict694in Ref. 2; AAH21747

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK146238
EMBL· GenBank· DDBJ
BAE27003.1
EMBL· GenBank· DDBJ
mRNA
AK165857
EMBL· GenBank· DDBJ
BAE38417.1
EMBL· GenBank· DDBJ
mRNA
BC021747
EMBL· GenBank· DDBJ
AAH21747.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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