Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 6.1.1.15 extracted from

  • Lee, E.Y.; Lee, H.C.; Kim, H.K.; Jang, S.Y.; Park, S.J.; Kim, Y.H.; Kim, J.H.; Hwang, J.; Kim, J.H.; Kim, T.H.; Arif, A.; Kim, S.Y.; Choi, Y.K.; Lee, C.; Lee, C.H.; Jung, J.U.; Fox, P.L.; Kim, S.; Lee, J.S.; Kim, M.H.
    Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity (2016), Nat. Immunol., 17, 1252-1262 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 6.1.1.15

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli BL21-CodonPlus (DE3) cells and HEK-293T cells Mus musculus
quantitative real-time PCR enzyme expression analysis, recombinant expression of tagged wild-type and mutant enzymes in Escherichia coli strain Escherichia coli BL21-CodonPlus (DE3)-RIPL Homo sapiens
quantitative real-time PCR enzyme expression analysis, recombinant expression of tagged wild-type and mutant enzymes in Escherichia coli strain Escherichia coli BL21-CodonPlus (DE3)-RIPL Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information siRNA-mediated enzyme knockout in HEK-293T cells. Cells in which EPRS is knocked down show considerable attenuation of the production of antiviral cytokines (IFN-beta and interleukin-6) following viral infection or treatment with the synthetic double-stranded RNA poly(I:C). Activation of the interferon-related signaling molecules IRF3 and STAT1 is significantly lower in cells in which EPRS is knocked down than in their EPRS-sufficient counterparts Homo sapiens
additional information siRNA-mediated enzyme knockout in RAW-264.7 cells. Activation of the interferon-related signaling molecules IRF3 and STAT1 is significantly lower in cells in which EPRS is knocked down than in their EPRS-sufficient counterparts . RAW-264.7 cells stably overexpressing EPRS show significantly less viral replication and more production of IFN-beta and interleukin-6 following infection with PR8 or VSV than those of their counterparts with basal expression of EPRS Mus musculus
R1152L catalytically inactive Mus musculus
R201L/R395L/S434A/K435L catalytic mutant Mus musculus
S886D phosphomimetic mutant Mus musculus
S886D/S990D phosphomimetic mutant Mus musculus
S886D/S999D phosphomimetic mutant Mus musculus
S990A phosphorylation-resistant mutant Mus musculus
S990A site-directed mutagenesis, the mutant is unable to rescue virus-infected cells Homo sapiens
S990A site-directed mutagenesis, the mutant is unable to rescue virus-infected cells Mus musculus
S990D phosphomimetic mutant Mus musculus
S990D site-directed mutagenesis, the mutation markedly inhibits viral replication in cells Homo sapiens
S990D site-directed mutagenesis, the mutation markedly inhibits viral replication in cells Mus musculus
S999D phosphomimetic mutant Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
cytoplasm
-
 Homo sapiens 5737
-
cytoplasm
-
 Mus musculus 5737
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-glutamate + tRNAGlu Mus musculus
-
 AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
ATP + L-glutamate + tRNAGlu Mus musculus C57BL/6
-
 AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAGlu Homo sapiens
-
 AMP + diphosphate + L-prolylyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAGlu Mus musculus
-
 AMP + diphosphate + L-prolylyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAGlu Mus musculus C57BL/6
-
 AMP + diphosphate + L-prolylyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAPro Mus musculus
-
 AMP + diphosphate + L-prolyl-tRNAPro
-
 ?
ATP + L-proline + tRNAPro Mus musculus C57BL/6
-
 AMP + diphosphate + L-prolyl-tRNAPro
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P07814
-
-
Mus musculus Q8CGC7
-
-
Mus musculus C57BL/6 Q8CGC7
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
phosphoprotein
-
 Mus musculus
phosphoprotein infection-specific phosphorylation of EPRS at a Ser induces its dissociation from the MSC, after which it is guided to the antiviral signaling pathway, where it interacts with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity Homo sapiens
phosphoprotein infection-specific phosphorylation of EPRS at Ser990 induces its dissociation from the MSC, after which it is guided to the antiviral signaling pathway, where it interacts with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity Mus musculus

Purification (Commentary)

Purification (Comment) Organism
glutathione Sepharose column chromatography Mus musculus
recombinant tagged wild-type and mutant enzymes from Escherichia coli strain Escherichia coli BL21-CodonPlus (DE3)-RIPL by affinity chromatography and gel filtration Homo sapiens
recombinant tagged wild-type and mutant enzymes from Escherichia coli strain Escherichia coli BL21-CodonPlus (DE3)-RIPL by affinity chromatography and gel filtration Mus musculus

Source Tissue

Source Tissue Comment Organism Textmining
HEK-293T cell
-
 Homo sapiens
-
macrophage
-
 Homo sapiens
-
macrophage
-
 Mus musculus
-
RAW-264.7 cell
-
 Mus musculus
-
RAW264.7 cell
-
 Mus musculus
-
U-937 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-glutamate + tRNAGlu
-
 Mus musculus AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
ATP + L-glutamate + tRNAGlu
-
 Mus musculus C57BL/6 AMP + diphosphate + L-glutamyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAGlu
-
 Homo sapiens AMP + diphosphate + L-prolylyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAGlu
-
 Mus musculus AMP + diphosphate + L-prolylyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAGlu
-
 Mus musculus C57BL/6 AMP + diphosphate + L-prolylyl-tRNAGlu
-
 ?
ATP + L-proline + tRNAPro
-
 Mus musculus AMP + diphosphate + L-prolyl-tRNAPro
-
 ?
ATP + L-proline + tRNAPro
-
 Mus musculus C57BL/6 AMP + diphosphate + L-prolyl-tRNAPro
-
 ?

Subunits

Subunits Comment Organism
More the enzyme is part of a multi-tRNA synthetase complex (MSC) Homo sapiens
More the enzyme is part of a multi-tRNA synthetase complex (MSC) Mus musculus

Synonyms

Synonyms Comment Organism
bifunctional aminoacyl-tRNA synthetase UniProt Homo sapiens
bifunctional aminoacyl-tRNA synthetase UniProt Mus musculus
bifunctional glutamate/proline-tRNA ligase UniProt Homo sapiens
bifunctional glutamate/proline-tRNA ligase UniProt Mus musculus
EPRS
-
 Homo sapiens
EPRS
-
 Mus musculus
glutamyl-prolyl tRNA synthetase
-
 Homo sapiens
glutamyl-prolyl tRNA synthetase
-
 Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens
37
-
 assay at Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Homo sapiens
7.5
-
 assay at Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Homo sapiens
ATP
-
 Mus musculus

Expression

Organism Comment Expression
Mus musculus both enzyme mRNA and protein are slightly upregulated following viral infection up
Homo sapiens requirement for sensing by the immune system in the induction of EPRS expression during infection with an RNA virus up
Mus musculus requirement for sensing by the immune system in the induction of EPRS expression during infection with an RNA virus, VSV Indiana strain up

General Information

General Information Comment Organism
malfunction EPRS-haploid (Eprs+/-) mice show enhanced viremia and inflammation and delayed viral clearance Mus musculus
malfunction glutamyl-prolyl-tRNA synthetase-haploid (Eprs+/-) mice show enhanced viremia and inflammation and delayed viral clearance Mus musculus
metabolism under conditions of stress, several MSC components, including EPRS, methionyl-tRNA synthetase (MRS), lysyl-tRNA synthetase (KRS), AIMP1 and AIMP2, are released from the complex through post-translational modifications to exert activities during non-translational events such as inflammation, cell metabolism, angiogenesis, and tumorigenesis. Phosphorylation is the critical regulatory mechanism that determines the non-translational function of ARSs in cells, overview Homo sapiens
metabolism under conditions of stress, several MSC components, including EPRS, methionyl-tRNA synthetase (MRS), lysyl-tRNA synthetase (KRS), AIMP1 and AIMP2, are released from the complex through post-translational modifications to exert activities during non-translational events such as inflammation, cell metabolism, angiogenesis, and tumorigenesis. Phosphorylation is the critical regulatory mechanism that determines the non-translational function of ARSs in cells, overview Mus musculus
additional information the enzyme is part of a multi-tRNA synthetase complex (MSC) Homo sapiens
additional information the enzyme is part of a multi-tRNA synthetase complex (MSC) Mus musculus
physiological function the enzyme regulates immune responses to viral infection and is critical for antiviral immunity in vivo Mus musculus
physiological function the multi-tRNA synthetase complex (MSC) component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at a Ser induces its dissociation from the MSC, after which it is guided to the antiviral signaling pathway, where it interacts with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. EPRS protects MAVS from PCBP2-mediated ubiquitination. The stimulus-inducible activation of MAVS by enzyme EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection. Phosphorylation of EPRS at a Ser is the driving force that leads to the antiviral roles of EPRS in regulating MAVS Homo sapiens
physiological function the multi-tRNA synthetase complex (MSC) component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induces its dissociation from the MSC, after which it is guided to the antiviral signaling pathway, where it interacts with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. EPRS protects MAVS from PCBP2-mediated ubiquitination. The stimulus-inducible activation of MAVS by enzyme EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection. Phosphorylation of EPRS at Ser990 is the driving force that leads to the antiviral roles of EPRS in regulating MAVS Mus musculus