Bifunctional glutamate/proline--tRNA ligase (P07814)

Uniprot ID P07814
Protein Name Bifunctional glutamate/proline--tRNA ligase
Gene Name EPRS
Species Homo sapiens (Human)
Signal peptide(a) N Secretome P(b) 0.381
Function Multifunctional protein which is primarily part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex, that catalyzes the attachment of the cognate amino acid to the corresponding tRNA in a two-step reaction: the amino acid is first activated by ATP to form a covalent intermediate with AMP and is then transferred to the acceptor end of the cognate tRNA (PubMed:1756734, PubMed:24100331, PubMed:23263184). The phosphorylation of EPRS, induced by interferon-gamma, dissociates the protein from the aminoacyl-tRNA synthetase multienzyme complex and recruits it to the GAIT complex that binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin), suppressing their translation. Interferon-gamma can therefore redirect, in specific cells, the EPRS function from protein synthesis to translation inhibition (PubMed:15479637, PubMed:23071094). Also functions as an effector of the mTORC1 signaling pathway by promoting, through SLC27A1, the uptake of long-chain fatty acid by adipocytes. Thereby, it also plays a role in fat metabolism and more indirectly influences lifespan (PubMed:28178239). .
GO - Molecular function
  • ATP binding : IEA:UniProtKB-KW
  • glutamate-tRNA ligase activity : IBA:GO_Central
  • GTPase binding : IPI:UniProtKB
  • identical protein binding : IPI:IntAct
  • proline-tRNA ligase activity : IDA:UniProtKB
  • protein homodimerization activity : IPI:UniProtKB
  • RNA stem-loop binding : IDA:UniProtKB
  • zinc ion binding : IDA:UniProtKB
GO - Biological process
  • cellular response to insulin stimulus : ISS:UniProtKB
  • cellular response to interferon-gamma : IDA:UniProtKB
  • glutamyl-tRNA aminoacylation : IBA:GO_Central
  • long-chain fatty acid import : IMP:UniProtKB
  • negative regulation of translation : IDA:UniProtKB
  • prolyl-tRNA aminoacylation : IDA:UniProtKB
  • protein-containing complex assembly : TAS:ProtInc
  • tRNA aminoacylation for protein translation : TAS:Reactome
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(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.
(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.