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MGP000975

UniProt Annotations

Entry Information
Gene Nameglutamyl-prolyl-tRNA synthetase
Protein EntrySYEP_HUMAN
UniProt IDP07814
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP + L-glutamate + tRNA(Glu) = AMP + diphosphate + L-glutamyl-tRNA(Glu).
Catalytic ActivityATP + L-proline + tRNA(Pro) = AMP + diphosphate + L-prolyl-tRNA(Pro).
CautionWas originally thought to be a glutaminyl-tRNA synthetase. {ECO:0000305}.
DomainThe WHEP-TRS domain is involved in RNA binding.
FunctionCatalyzes 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. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation and subsequent phosphorylation dissociates from the multisynthetase complex and assembles into the GAIT complex which binds to stem loop- containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:1756734, ECO:0000269|PubMed:23071094}.
InteractionP41252:IARS; NbExp=5; IntAct=EBI-355315, EBI-355303;
PtmPhosphorylated at Ser-886 by CDK5 and at Ser-999 by an unknown kinase in a IFN-gamma-dependent manner in monocytes; these sequential phosphorylations are causing release from the multisynthetase complex, association with the GAIT complex and subsequent involvement in transcript-selective translation inhibition. Phosphorylation at Ser-999 is specifically required for the interaction of GAIT complex-associated RPL13A with eIF4G. {ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19647514, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21220307, ECO:0000269|PubMed:21406692}.
Sequence CautionSequence=AAH15494.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH34797.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH46156.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAH58921.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=AAS72877.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=CAA30354.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305}; Sequence=CAA38224.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
SimilarityContains 3 WHEP-TRS domains. {ECO:0000305}.
SimilarityIn the C-terminal section; belongs to the class-II aminoacyl-tRNA synthetase family. {ECO:0000305}.
SimilarityIn the N-terminal section; belongs to the class-I aminoacyl-tRNA synthetase family. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000305}.
SubunitComponent of the multisynthetase complex which is comprised of a bifunctional glutamyl-prolyl-tRNA synthetase, the monospecific isoleucyl, leucyl, glutaminyl, methionyl, lysyl, arginyl, and aspartyl-tRNA synthetases as well as three auxiliary proteins, p18, p48 and p43. Interacts with DUS2L. Component of the GAIT complex; in humans the complex assembly seems to be a two- step process in which EPRS first associates with SYNCRIP to form a pre-GAIT complex which is deficient in GAIT element binding. {ECO:0000269|PubMed:15479637, ECO:0000269|PubMed:15994936, ECO:0000269|PubMed:19647514}.
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