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Information on EC 6.1.1.15 - proline-tRNA ligase and Organism(s) Homo sapiens
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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
-
aarss
-
misactivated
-
multisynthetase
-
misacylated
-
trans-editing
-
cys-trnapro
- trnacys
- thrrs
-
mistranslation
- thermautotrophicus
-
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: Homo sapiens
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
EPRS
Global RNA synthesis factor
glutamyl-prolyl tRNA synthetase
Pro-tRNA synthetase
Proline translase
Proline--tRNA ligase
Prolyl RNA synthetase
Prolyl-transfer ribonucleate synthetase
Prolyl-transfer ribonucleic acid synthetase
Prolyl-transfer RNA synthetase
Prolyl-tRNA synthetase
ProRS
Global RNA synthesis factor
-
-
-
-
Pro-tRNA synthetase
-
-
-
-
Proline translase
-
-
-
-
Proline--tRNA ligase
-
-
-
-
Prolyl RNA synthetase
-
-
-
-
Prolyl-transfer ribonucleate synthetase
-
-
-
-
Prolyl-transfer ribonucleic acid synthetase
-
-
-
-
Prolyl-transfer RNA synthetase
-
-
-
-
Prolyl-tRNA synthetase
-
-
-
-
ProRS
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Aminoacylation
esterification
Aminoacylation
-
-
-
-
esterification
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-proline:tRNAPro ligase (AMP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY
9055-68-9
-
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-alanine + tRNAPro
AMP + diphosphate + L-alanyl-tRNAPro
-
very low activity
-
?
ATP + L-proline + tRNAPro
AMP + diphosphate + L-prolyl-tRNAPro
-
-
-
-
?
ATP + L-proline + tRNAPro
AMP + diphosphate + L-prolyl-tRNAPro
-
-
-
?
ATP + L-proline + tRNAPro
AMP + diphosphate + L-prolyl-tRNAPro
-
semi-synthetic human tRNAPro prepared by annealing a 5'-57-mer fragment to a 3'-16-mer. The 5'-57-mer is prepared by in vitro transcription
-
-
?
additional information
?
-
-
no activity with L-cysteine, the enzyme also performs the ATP-diphosphate exchange reaction, enzyme possesses no editing activity against L-alanine and to prevent from misincorporation of alanine into proteins
-
?
additional information
?
-
-
in addition to enzymic activity, glutamyl-prolyl-tRNA synthetase is phosphorylated in response to interferon-gamma, binds the ceruloplasmin 3'-untranslated region in an mRNP containing three additional proteins, and silences ceruloplasmin mRNA translation
-
-
?
additional information
?
-
-
the glutamyl-prolyl tRNA synthetase determines the specificity of the heterotetrameric GAIT complex suppressing translation of selected mRNAs in interferon-gamma-activated monocytic cells by binding to a 3' UTR element in target mRNAs, critical role of EPRS WHEP domains in targeting and regulating GAIT complex binding to RNA, mechanism, overview. The enzyme is essential in regulating inflammatory gene expression
-
-
?
additional information
?
-
-
determination of Pro-AMP and Ala-AMP hydrolysis activities, overview
-
-
?
additional information
?
-
-
substrate specificity, reducing effects of diverse different phosphorothioate substitutions in the 3'-strand of human tRNAPro on aminoacylation efficiency, mechanism, overview
-
-
?
additional information
?
-
-
the upstream WHEP pair of EPRS directs high-affinity binding to GAIT element-bearing mRNAs, while the overlapping, downstream pair binds NSAP1, which inhibits mRNA binding. Interaction of EPRS with ribosomal protein L13a and GAPDH induces a conformational witch that rescues mRNA binding and restores translational control, interaction analysis, overview
-
-
?
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-proline + tRNAPro
AMP + diphosphate + L-prolyl-tRNAPro
-
-
-
-
?
ATP + L-proline + tRNAPro
AMP + diphosphate + L-prolyl-tRNAPro
-
-
-
?
additional information
?
-
-
in addition to enzymic activity, glutamyl-prolyl-tRNA synthetase is phosphorylated in response to interferon-gamma, binds the ceruloplasmin 3'-untranslated region in an mRNP containing three additional proteins, and silences ceruloplasmin mRNA translation
-
-
?
additional information
?
-
-
the glutamyl-prolyl tRNA synthetase determines the specificity of the heterotetrameric GAIT complex suppressing translation of selected mRNAs in interferon-gamma-activated monocytic cells by binding to a 3' UTR element in target mRNAs, critical role of EPRS WHEP domains in targeting and regulating GAIT complex binding to RNA, mechanism, overview. The enzyme is essential in regulating inflammatory gene expression
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-(4-bromo-phenyl)-5-methyl-7-chloro-4-quinolinecarboxylic acid
-
weak inhibition
2-(4-bromo-phenyl)-6-(trifluoromethoxy)-4-quinolinecarboxylic acid
-
weak inhibition
2-(4-bromo-phenyl)-6-chloro-8-hydroxymethyl-4-quinolinecarboxylic acid
-
weak inhibition
3-(3,3-dimethylbutanamido)-N-[(naphthalen-1-yl)methyl]pyrazine-2-carboxamide
-
3-[(cyclohexanecarbonyl)amino]-N-(2,3-dihydro-1H-inden-2-yl)pyrazine-2-carboxamide
-
N-[(4-chlorophenyl)methyl]-3-[(cyclohexanecarbonyl)amino]pyrazine-2-carboxamide
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.11
3-(3,3-dimethylbutanamido)-N-[(naphthalen-1-yl)methyl]pyrazine-2-carboxamide
Homo sapiens
at pH 7.5 and 25°C
0.012
3-[(cyclohexanecarbonyl)amino]-N-(2,3-dihydro-1H-inden-2-yl)pyrazine-2-carboxamide
Homo sapiens
at pH 7.5 and 25°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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
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
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
additional information
the enzyme is part of a multi-tRNA synthetase complex (MSC)
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). SYPM_HUMAN
475
0
53263
Swiss-Prot
Mitochondrion (Reliability: 3)
SYEP_HUMAN
1512
0
170591
Swiss-Prot
other Location (Reliability: 3)
B4DP50_HUMAN
476
0
54143
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
glutamyl-prolyl-tRNA synthetase is a component of the interferon gamma-activated inhibitor of translation complex
additional information
-
the human EPRS consists of four major domains: an N-terminal elongation factor-1Bgamma-like domain, an ERS catalytic domain, a 300 amino acid linker domain containing three tandem WHEP domains, and a C-terminal PRS catalytic domain
additional information
the enzyme is part of a multi-tRNA synthetase complex (MSC)
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
phosphoprotein
-
glutamyl-prolyl-tRNA synthetase is phosphorylated in response to interferon-gamma
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complexed with ATP and L-proline or halofuginone, hanging drop vapor diffusion method, using 0.1 M sodium cacodylate, 1.0 M sodium citrate dibasic trihydrate pH 6.5
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A57G
-
site-directed mutagenesis, the A57G mutation introduces a BstBI restriction site within the gene, but has no effect on catalytic activity
F1097A
the mutant shows strongly decreased aminoacylation activity compared to the wild type enzyme
F1097W
the mutant shows increased aminoacylation activity compared to the wild type enzyme
R1152K
the mutant shows increased aminoacylation activity compared to the wild type enzyme
R1152L
the mutant shows strongly decreased aminoacylation activity compared to the wild type enzyme
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 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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
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
requirement for sensing by the immune system in the induction of EPRS expression during infection with an RNA virus
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kerjan, P.; Triconnet, M.; Waller, J.P.
Mammalian prolyl-tRNA synthetase corresponds to the approximately 150 kDa subunit of the high-Mr aminoacyl-tRNA synthetase complex
Biochimie
74
195-205
1992
Ovis aries, Homo sapiens, Mammalia
Yu, X.Y.; Hill, J.M.; Yu, G.; Yang, Y.; Kluge, A.F.; Keith, D.; Finn, J.; Gallant, P.; Silverman, J.; Lim, A.
A series of quinoline analogues as potent inhibitors of C. albicans prolyl tRNA synthetase
Bioorg. Med. Chem. Lett.
11
541-544
2001
Candida albicans, Homo sapiens
Beuning, P.J.; Musier-Forsyth, K.
Species-specific differences in amino acid editing by class II prolyl-tRNA synthetase
J. Biol. Chem.
276
30779-30785
2001
Escherichia coli, Homo sapiens, Methanocaldococcus jannaschii
Sampath, P.; Mazumder, B.; Seshadri, V.; Gerber, C.A.; Chavatte, L.; Kinter, M.; Ting, S.M.; Dignam, J.D.; Kim, S.; Driscoll, D.M.; Fox, P.L.
Noncanonical function of glutamyl-prolyl-tRNA synthetase: Gene-specific silencing of translation
Cell
119
195-208
2004
Homo sapiens
Splan, K.E.; Ignatov, M.E.; Musier-Forsyth, K.
Transfer RNA modulates the editing mechanism used by class II prolyl-tRNA synthetase
J. Biol. Chem.
283
7128-7134
2008
Escherichia coli, Homo sapiens, Methanocaldococcus jannaschii
Jia, J.; Arif, A.; Ray, P.S.; Fox, P.L.
WHEP domains direct noncanonical function of glutamyl-prolyl tRNA synthetase in translational control of gene expression
Mol. Cell
29
679-690
2008
Homo sapiens
An, S.; Barany, G.; Musier-Forsyth, K.
Evolution of acceptor stem tRNA recognition by class II prolyl-tRNA synthetase
Nucleic Acids Res.
36
2514-2521
2008
Homo sapiens
Son, J.; Lee, E.H.; Park, M.; Kim, J.H.; Kim, J.; Kim, S.; Jeon, Y.H.; Hwang, K.Y.
Conformational changes in human prolyl-tRNA synthetase upon binding of the substrates proline and ATP and the inhibitor halofuginone
Acta Crystallogr. Sect. D
69
2136-2145
2013
Homo sapiens (P07814), Homo sapiens
Keller, T.L.; Zocco, D.; Sundrud, M.S.; Hendrick, M.; Edenius, M.; Yum, J.; Kim, Y.J.; Lee, H.K.; Cortese, J.F.; Wirth, D.F.; Dignam, J.D.; Rao, A.; Yeo, C.Y.; Mazitschek, R.; Whitman, M.
Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase
Nat. Chem. Biol.
8
311-317
2012
Homo sapiens
Adachi, R.; Okada, K.; Skene, R.; Ogawa, K.; Miwa, M.; Tsuchinaga, K.; Ohkubo, S.; Henta, T.; Kawamoto, T.
Discovery of a novel prolyl-tRNA synthetase inhibitor and elucidation of its binding mode to the ATP site in complex with L-proline
Biochem. Biophys. Res. Commun.
488
393-399
2017
Homo sapiens (P07814), Homo sapiens
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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