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Information on EC 6.1.1.15 - proline-tRNA ligase and Organism(s) Mus musculus and UniProt Accession Q8CGC7
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6.1.1.15 proline-tRNA ligaseSpecify your search results
Word Map
- 6.1.1.15
- synthetases
- aminoacylation
- halofuginone
-
ala-trnapro
-
anticodons
-
mischarged
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aarss
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misactivated
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multisynthetase
-
misacylated
-
trans-editing
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cys-trnapro
- trnacys
- thrrs
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mistranslation
- thermautotrophicus
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multi-trna
- glnrs
- leucyl-trna
- lysyl-trna
- leurs
- asprs
- febrifugine
-
post-transfer
-
transcript-selective
- drug development
- pharmacology
The taxonomic range for the selected organisms is: Mus musculus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
prors, prolyl-trna synthetase, glutamyl-prolyl-trna synthetase, glutamyl-prolyl trna synthetase, gluprors, prolyl trna synthetase, prorstt, procysrs, bifunctional aminoacyl-trna synthetase, class ii prolyl-trna synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Global RNA synthesis factor
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-
-
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Pro-tRNA synthetase
-
-
-
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Proline translase
-
-
-
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Proline--tRNA ligase
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-
-
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Prolyl RNA synthetase
-
-
-
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Prolyl-transfer ribonucleate synthetase
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-
-
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Prolyl-transfer ribonucleic acid synthetase
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-
-
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Prolyl-transfer RNA synthetase
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-
-
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Prolyl-tRNA synthetase
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-
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ProRS
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
esterification
-
-
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Aminoacylation
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-proline:tRNAPro ligase (AMP-forming)
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CAS REGISTRY NUMBER
COMMENTARY
9055-68-9
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + L-glutamate + tRNAGlu
AMP + diphosphate + L-glutamyl-tRNAGlu
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-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + L-glutamate + tRNAGlu
AMP + diphosphate + L-glutamyl-tRNAGlu
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
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
physiological function
physiological function
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mechanism of translation control of enzyme EPRS involving increased translation initiation stringency during stress-induced eIF2alpha-P, facilitated ribosome bypass of upstream ORFs, allowing for increased translation of the EPRS coding region. The 5'-leader of the EPRS mRNA directs preferential translation. Although a portion of the ribosomes that translate uORF2 can reinitiate downstream, scanning ribosomes also bypass uORF2 because of its noncanonical UUG1 initiation codon and initiate translation at the downstream coding sequence. UUG1 and CUG2 are overall repressing elements in EPRS translation control. Model for EPRS translation control, overview
additional information
the enzyme is part of a multi-tRNA synthetase complex (MSC)
malfunction
EPRS-haploid (Eprs+/-) mice show enhanced viremia and inflammation and delayed viral clearance
malfunction
glutamyl-prolyl-tRNA synthetase-haploid (Eprs+/-) mice show enhanced viremia and inflammation and delayed viral clearance
physiological function
the enzyme regulates immune responses to viral infection and is critical for antiviral immunity in vivo
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SYEP_MOUSE
1512
0
170079
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the enzyme is part of a multi-tRNA synthetase complex (MSC)
additional information
-
enzyme is part of a high molecular mass aminoacyl-tRNA synthetase complex, which has a coherent structure that can be visualized by electron microscopy
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
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
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S990A
S990D
additional information
S990A
site-directed mutagenesis, the mutant is unable to rescue virus-infected cells
S990D
site-directed mutagenesis, the mutation markedly inhibits viral replication in cells
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
additional information
-
transfection of MEF cells with the PTK-EPRS-Luc reporter followed by either halofuginone treatment or no treatment
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant tagged wild-type and mutant enzymes from Escherichia coli strain Escherichia coli BL21-CodonPlus (DE3)-RIPL by affinity chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21-CodonPlus (DE3) cells and HEK-293T cells
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
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
both enzyme mRNA and protein are slightly upregulated following viral infection
requirement for sensing by the immune system in the induction of EPRS expression during infection with an RNA virus, VSV Indiana strain
the translation of the glutamyl-prolyl-tRNA synthetase gene EPRS is enhanced in response to phosphorylated eukaryotic initiation factor 2, eIF2alpha-P, mechanism of translation control involving increased translation initiation stringency during stress-induced eIF2alpha-P, facilitated ribosome bypass of upstream ORFs, allowing for increased translation of the EPRS coding region, overview. Both halofuginone and thapsigargin treatment result in a 2.5fold induction of EPRS expression
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Norcum, M.T.
Isolation and electron microscopic characterization of the high molecular mass aminoacyl-tRNA synthetase complex from murine erythroleukemia cells
J. Biol. Chem.
264
15043-15051
1989
Mus musculus
Young, S.K.; Baird, T.D.; Wek, R.C.
Translation regulation of the glutamyl-prolyl-tRNA synthetase gene EPRS through bypass of upstream open reading frames with noncanonical initiation codons
J. Biol. Chem.
291
10824-10835
2016
Mus musculus
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
Nat. Immunol.
17
1252-1262
2016
Homo sapiens (P07814), Mus musculus (Q8CGC7), Mus musculus C57BL/6 (Q8CGC7)
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