GARS1

Protein identityUniProt · HPA

UniProt accession

P41250

Gene

GARS1

Ensembl

ENSG00000106105

Chromosome

7

Canonical length

739 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

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. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Canonical amino-acid sequenceUniProt

739 residues, UniProt reviewed canonical sequence.

>P41250|GARS1
     1  MPSPRPVLLR GARAALLLLL PPRLLARPSL LLRRSLSAAS CPPISLPAAA SRSSMDGAGA
    61  EEVLAPLRLA VRQQGDLVRK LKEDKAPQVD VDKAVAELKA RKRVLEAKEL ALQPKDDIVD
   121  RAKMEDTLKR RFFYDQAFAI YGGVSGLYDF GPVGCALKNN IIQTWRQHFI QEEQILEIDC
   181  TMLTPEPVLK TSGHVDKFAD FMVKDVKNGE CFRADHLLKA HLQKLMSDKK CSVEKKSEME
   241  SVLAQLDNYG QQELADLFVN YNVKSPITGN DLSPPVSFNL MFKTFIGPGG NMPGYLRPET
   301  AQGIFLNFKR LLEFNQGKLP FAAAQIGNSF RNEISPRSGL IRVREFTMAE IEHFVDPSEK
   361  DHPKFQNVAD LHLYLYSAKA QVSGQSARKM RLGDAVEQGV INNTVLGYFI GRIYLYLTKV
   421  GISPDKLRFR QHMENEMAHY ACDCWDAESK TSYGWIEIVG CADRSCYDLS CHARATKVPL
   481  VAEKPLKEPK TVNVVQFEPS KGAIGKAYKK DAKLVMEYLA ICDECYITEM EMLLNEKGEF
   541  TIETEGKTFQ LTKDMINVKR FQKTLYVEEV VPNVIEPSFG LGRIMYTVFE HTFHVREGDE
   601  QRTFFSFPAV VAPFKCSVLP LSQNQEFMPF VKELSEALTR HGVSHKVDDS SGSIGRRYAR
   661  TDEIGVAFGV TIDFDTVNKT PHTATLRDRD SMRQIRAEIS ELPSIVQDLA NGNITWADVE
   721  ARYPLFEGQE TGKKETIEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GARS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

75 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GARS1.

Disease | AllUniProt

Conditions GARS1 is implicated in, by any mechanism.

• Charcot-Marie-Tooth disease, axonal, type 2D (CMT2D) MIM:601472
• Neuronopathy, distal hereditary motor, autosomal dominant 5 (HMND5) MIM:600794
• Spinal muscular atrophy, infantile, James type (SMAJI) MIM:619042

Disease | GeneticClinVar

30 pathogenic / likely-pathogenic of 900 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Charcot-Marie-Tooth disease type 2
• Charcot-Marie-Tooth disease type 2D
• Neuronopathy, distal hereditary motor, type 5A
• Charcot-Marie-Tooth disease
• Distal spinal muscular atrophy

Disease | AutoantibodyPubMed

Conditions in which antibodies against GARS1 are reported. Each links to that disease's full target list.

• Lung Diseases, Interstitial 4
• Myositis 3

ReferencesPubMed · IEDB

Publications for GARS1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.4

gnomAD pLI

0.31

DepMap mean gene effect

-1.37

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• diadenosine tetraphosphate biosynthetic process
• tRNA aminoacylation for protein translation
• mitochondrial glycyl-tRNA aminoacylation

Molecular functions

• ATP binding
• bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) activity
• identical protein binding
• protein dimerization activity
• ATP:ATP adenylyltransferase activity
• glycine-tRNA ligase activity

Cellular components

• axon
• cytoplasm
• cytosol
• extracellular exosome
• mitochondrial matrix
• mitochondrion
• secretory granule

Protein domainsUniProt · Pfam · InterPro

• WHEP-TRS domain
• Aminoacyl-tRNA synthetase, class II (G/ P/ S/T)
• Anticodon-binding
• Aminoacyl-tRNA synthetase, class II
• uS15/NS1, RNA-binding domain superfamily
• Glycyl-tRNA synthetase/DNA polymerase subunit gamma-2
• Anticodon-binding domain superfamily
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• WHEP-TRS domain
• tRNA synthetase class II core domain (G, H, P, S and T)
• Anticodon binding domain
• Glycyl-tRNA synthetase
• Glycyl-tRNA synthetase-like core domain

KeywordsUniProt

• Acetylation
• Alternative initiation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Cell projection
• Charcot-Marie-Tooth disease
• Cytoplasm
• Hydrolase
• Ligase
• Mitochondrion
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Phosphoprotein
• Protein biosynthesis
• Secreted
• Transferase
• Transit peptide