EPRS1 glutamyl-prolyl-tRNA synthetase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: EPRS1provided by HGNC
Official Full Name: glutamyl-prolyl-tRNA synthetase 1provided by HGNC
Primary source: HGNC:HGNC:3418
See related: Ensembl:ENSG00000136628 MIM:138295; AllianceGenome:HGNC:3418
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EARS; EPRS; PARS; QARS; QPRS; HLD15; PIG32; GLUPRORS
Summary: 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]
Expression: Ubiquitous expression in thyroid (RPKM 31.6), appendix (RPKM 22.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q41

Exon count:: 32

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (219968600..220046505, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (219207867..219285874, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (220141942..220219847, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m[6]A site accessibility.
Title: Homozygous EPRS1 missense variant causing hypomyelinating leukodystrophy-15 alters variant-distal mRNA m(6)A site accessibility.
Glutamyl-prolyl-tRNA synthetase (EPRS1) drives tubulointerstitial nephritis-induced fibrosis by enhancing T cell proliferation and activity.
Title: Glutamyl-prolyl-tRNA synthetase (EPRS1) drives tubulointerstitial nephritis-induced fibrosis by enhancing T cell proliferation and activity.
Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma.
Title: Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma.
Disease-associated mutations in a bifunctional aminoacyl-tRNA synthetase gene elicit the integrated stress response.
Title: Disease-associated mutations in a bifunctional aminoacyl-tRNA synthetase gene elicit the integrated stress response.
Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis.
Title: Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis.
The human glutamyl-prolyl-tRNA synthetase (EPRS) consisting of two fused synthetases .This study identified site-selective proteolysis as a mechanism that severs the linkage between the EPRS synthetases in vitro and in vivo Caspase action targeted Asp-929 in the third WHEP domain, thereby separating the two synthetases.
Title: Structural control of caspase-generated glutamyl-tRNA synthetase by appended noncatalytic WHEP domains.
five different EPRS mutations were identified.
Title: Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy.
Data indicate the necessity of EPRS for proliferation of tamoxifen-resistant estrogen receptor (ER+) breast cancer, but not ER- breast cancer cells.
Title: EPRS is a critical regulator of cell proliferation and estrogen signaling in ER+ breast cancer.
analysis of the heterotetrameric complex structure of the glutathione transferase (GST) domains shared among the four MSC components, methionyl-tRNA synthetase (MRS), glutaminyl-prolyl-tRNA synthetase (EPRS), AIMP2 and AIMP3
Title: Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains.
Dynamic model simulations predicted an inhibitory GAIT-element-interacting factor to account for this relationship and led to the identification of a truncated form of EPRS, a GAIT constituent that mediates binding to target transcripts.
Title: Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Leukodystrophy, hypomyelinating, 15 MedGen: C4693733 OMIM: 617951 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify glutamyl-prolyl-tRNA synthetase (EPRS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify glutamyl-prolyl-tRNA synthetase (EPRS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify glutamyl-prolyl-tRNA synthetase (EPRS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Cellular biotinylated glutamyl-prolyl-tRNA synthetase (EPRS, Bifunctional glutamate/proline tRNA ligase) protein is incorporated into HIV-1 Gag virus-like particles	PubMed
	gag	Tandem affinity purification and mass spectrometry analysis identify glutamyl-prolyl-tRNA synthetase (EPRS), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
matrix	gag	HIV-1 MA is identified to have a physical interaction with glutamyl-prolyl-tRNA synthetase (EPRS) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-79732 (e-PCR)
- UniSTS:96001

G34844 (e-PCR)
- UniSTS:15385

AL033652 (e-PCR)
- UniSTS:93487

HUM000S513 (e-PCR)
- UniSTS:77524

SHGC-142608 (e-PCR)
- UniSTS:174045

SHGC-11953 (e-PCR)
- UniSTS:31714

G34812 (e-PCR)
- UniSTS:31715

RH70835 (e-PCR)
- UniSTS:39409

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GTPase binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA stem-loop binding	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-tRNA ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-tRNA ligase activity	TAS Traceable Author Statement more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables proline-tRNA ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables proline-tRNA ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables proline-tRNA ligase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to insulin stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to type II interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in glutamyl-tRNA aminoacylation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in prolyl-tRNA aminoacylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in prolyl-tRNA aminoacylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of long-chain fatty acid import into cell	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tRNA aminoacylation for protein translation	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
part_of GAIT complex	IDA Inferred from Direct Assay more info	PubMed
part_of aminoacyl-tRNA synthetase multienzyme complex	IBA Inferred from Biological aspect of Ancestor more info
part_of aminoacyl-tRNA synthetase multienzyme complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
part_of ribonucleoprotein complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: bifunctional glutamate/proline--tRNA ligase

Names: bifunctional aminoacyl-tRNA synthetase; cell proliferation-inducing gene 32 protein; glutamate tRNA ligase; glutamatyl-prolyl-tRNA synthetase; glutaminyl-tRNA synthetase; proliferation-inducing gene 32 protein; proliferation-inducing protein 32; proline-tRNA ligase; prolyl-tRNA synthetase

NP_004437.2

EC 6.1.1.15

EC 6.1.1.17

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_004446.3 → NP_004437.2 bifunctional glutamate/proline--tRNA ligase

See identical proteins and their annotated locations for NP_004437.2

Status: REVIEWED

Source sequence(s)

AA196283, AY493416, BC034797, BC046156, N85252

Consensus CDS

CCDS31027.1

UniProtKB/Swiss-Prot

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

Related

ENSP00000355890.3, ENST00000366923.8

Conserved Domains (9) summary

cd10309
Location:74 → 157

GST_C_GluProRS_N; Glutathione S-transferase C-terminal-like, alpha helical domain of bifunctional Glutamyl-Prolyl-tRNA synthetase

PLN02907
Location:13 → 711

PLN02907; glutamate-tRNA ligase

PRK08661
Location:1019 → 1512

PRK08661; prolyl-tRNA synthetase; Provisional

cd00778
Location:1023 → 1286

ProRS_core_arch_euk; Prolyl-tRNA synthetase (ProRS) class II core catalytic domain. ProRS is a homodimer. It is responsible for the attachment of proline to the 3' OH group of ribose of the appropriate tRNA. This domain is primarily responsible for ATP-dependent formation of ...

cd00862
Location:1292 → 1512

ProRS_anticodon_zinc; ProRS Prolyl-anticodon binding domain, long version found predominantly in eukaryotes and archaea. ProRS belongs to class II aminoacyl-tRNA synthetases (aaRS). This alignment contains the anticodon binding domain, which is responsible for specificity in ...

cd00936
Location:904 → 952

WEPRS_RNA; WEPRS_RNA binding domain. This short RNA-binding domain is found in several higher eukaryote aminoacyl-tRNA synthetases (aaRSs). It is found in multiple copies in eukaryotic bifunctional glutamyl-prolyl-tRNA synthetases (EPRS) in a region that separates ...

pfam00458
Location:753 → 805

WHEP-TRS; WHEP-TRS domain

pfam00749
Location:197 → 502

tRNA-synt_1c; tRNA synthetases class I (E and Q), catalytic domain

pfam03950
Location:504 → 681

tRNA-synt_1c_C; tRNA synthetases class I (E and Q), anti-codon binding domain