Tchem EPRS Bifunctional glutamate/proline--tRNA ligase

Protein Summary

Description

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). Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a multifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. Alternative splicing has been observed for this gene, but the full-length nature and biological validity of the variant have not been determined. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P07814
• A0AVA9
• B9EGH3
• Q05BP6
• Q05DF8
• Q5DSM1
• Q5H9S5
• Q6PD57
• Q86X73

Gene Name

• EPRS

Ensembl ID

• ENST00000366923
• ENSP00000355890
• ENSG00000136628

Symbol

• GLNS
• PARS
• QARS
• QPRS
• EARS
• PARS
• QARS
• QPRS
• HLD15
• PIG32
• GLUPRORS

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	1
protein domain	1
disease perturbation	0.99
hub protein	0.96
molecular function	0.95

Protein Classes

PANTHER Classes

Protein / Ligase / Bifunctional Glutamate/proline--trna Ligase

DTO Classes

Protein / Enzyme / Ligase / Bifunctional Glutamate/proline--trna Ligase

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1173.19   (req: < 5)

Gene RIFs: 11   (req: <= 3)

Antibodies: 165   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1173.19   (req: >= 5)

Gene RIFs: 11   (req: > 3)

Antibodies: 165   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 16

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (1)

Explore Active Ligands

1 – 1 of 1

CHEMBL357355

EPRSTchem Enzyme

pKi : 7.82

Protein-Protein Interactions (710)

Explore Interacting Targets

1 – 10 of 710

• See Interactions on String-DB

KARS

Tchem

Family:  Enzyme

Novelty:  0.00386511

p_int:  0.998884029

p_ni:  0.001115971

Score:  0.999

Data Source:  BioPlex,STRINGDB

AIMP1

Tbio

Family:  Enzyme

Novelty:  0.00743447

p_int:  0.996684787

p_ni:  0.003315213

Score:  0.999

Data Source:  BioPlex,STRINGDB

RARS

Tchem

Family:  Enzyme

Novelty:  0.00099479

p_int:  0.993858166

p_ni:  0.006141834

Score:  0.999

Data Source:  BioPlex,STRINGDB

LARS

Tchem

Family:  Enzyme

Novelty:  0.00361711

p_int:  0.989037048

p_ni:  0.010962952

Score:  0.999

Data Source:  BioPlex,STRINGDB

QARS

Tchem

Family:  Enzyme

Novelty:  0.01684657

p_int:  0.975918754

p_ni:  0.024081246

Score:  0.998

Data Source:  BioPlex,STRINGDB

SDCBP

Tbio

Novelty:  0.00242211

p_int:  0.953067398

p_ni:  0.046932602

Score:  0.809

Data Source:  BioPlex,STRINGDB

AIMP2

Tchem

Family:  Enzyme

Novelty:  0.03283387

Score:  0.999

Data Source:  STRINGDB

IARS

Tchem

Family:  Enzyme

Novelty:  0.00539046

Score:  0.999

Data Source:  STRINGDB

EEF1E1

Tbio

Novelty:  0.06216577

Score:  0.999

Data Source:  STRINGDB

DARS

Tbio

Family:  Enzyme

Novelty:  0.01101888

Score:  0.999

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (50)

Reactome (10)

KEGG (3)

PathwayCommons (5)

WikiPathways (32)

Cytosolic tRNA aminoacylation (R-HSA-379716)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytosolic tRNA aminoacylation	24 targets	R-HSA-379716
Reactome	Metabolism	2112 targets	R-HSA-1430728
Reactome	Metabolism of RNA	686 targets	R-HSA-8953854
Reactome	Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499

Name	Explore in Pharos	Explore in Source
Cytosolic tRNA aminoacylation	24 targets	R-HSA-379716
Metabolism	2112 targets	R-HSA-1430728
Metabolism of RNA	686 targets	R-HSA-8953854
Metabolism of amino acids and derivatives	373 targets	R-HSA-71291
Metabolism of proteins	2050 targets	R-HSA-392499

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (23)

Functions (8)

Components (7)

Processes (8)

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1 – 8 of 8

GO Term	Evidence	Assigned by
proline-tRNA ligase activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA stem-loop binding	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
GTPase binding	Inferred from Physical Interaction (IPI)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
protein homodimerization activity	Inferred from Physical Interaction (IPI)	UniProtKB
glutamate-tRNA ligase activity	Traceable Author Statement (TAS)	Reactome
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations ()

No disease associations found

GWAS Traits (13)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte count	EFO_0007986	7	4	7		93.1
heel bone mineral density	EFO_0009270	3	2	4		92.4
reticulocyte measurement	EFO_0010700	3	2	3		90.6
red blood cell distribution width	EFO_0005192	2	2	2		86.2
aspartate aminotransferase measurement	EFO_0004736	1	1	1		80.1

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
reticulocyte count	EFO_0007986	7		93.1
heel bone mineral density	EFO_0009270	4		92.4
reticulocyte measurement	EFO_0010700	3		90.6
red blood cell distribution width	EFO_0005192	2		86.2
aspartate aminotransferase measurement	EFO_0004736	1		80.1

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Aminoacyl-tRNA synthetase
ATP-binding
Complete proteome
Cytoplasm
Disease mutation
Leukodystrophy
Ligase
Membrane

GWAS Trait Find Similar Targets

No Header	No Header
aspartate aminotransferase measurement
ferritin measurement
glomerular filtration rate
heel bone mineral density
high density lipoprotein cholesterol measurement
hip circumference
liver disease biomarker
liver fat measurement
magnesium:calcium ratio
mathematical ability

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
cellular phenotype
embryo phenotype
growth/size/body region phenotype
homeostasis/metabolism phenotype
limbs/digits/tail phenotype
mortality/aging
respiratory system phenotype
skeleton phenotype

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	glutamyl-prolyl-tRNA synthetase	VGNC:1235	457746
Macaque	glutamyl-prolyl-tRNA synthetase		706899
Mouse	glutamyl-prolyl-tRNA synthetase	MGI:97838	107508
Rat	glutamyl-prolyl-tRNA synthetase	RGD:1310952	289352
Dog	glutamyl-prolyl-tRNA synthetase	VGNC:40425	478962

Species	Name	OMA	EggNOG	Inparanoid
Chimp	glutamyl-prolyl-tRNA synthetase
Macaque	glutamyl-prolyl-tRNA synthetase
Mouse	glutamyl-prolyl-tRNA synthetase
Rat	glutamyl-prolyl-tRNA synthetase
Dog	glutamyl-prolyl-tRNA synthetase

Publication Statistics

PubMed Score 1173.19

PubMed score by year

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PubTator Score 53.42

PubTator score by year

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Related Publications

Text Mined References (47)

GeneRif Annotations (11)

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PMID	Year	Title