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

    Gene ID: 2058, updated on 3-Nov-2024

    Summary

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    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

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    See EPRS1 in Genome Data Viewer
    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_000001.11Genomic Context describing neighboring genes Neighboring gene solute carrier family 30 member 10 Neighboring gene Sharpr-MPRA regulatory region 9893 Neighboring gene uncharacterized LOC107985281 Neighboring gene small nucleolar RNA U3 Neighboring gene small nucleolar RNA U13 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_4879 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:220200073-220200574 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:220219000-220219557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2551 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2552 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_4904 Neighboring gene 3'(2'), 5'-bisphosphate nucleotidase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2553 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 2554 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1822 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1823 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:220267703-220268202 Neighboring gene uncharacterized LOC105373475 Neighboring gene isoleucyl-tRNA synthetase 2, mitochondrial

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues 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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    Related articles in PubMed

    1. Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy. Mendes MI, et al. Am J Hum Genet, 2018 Apr 5. PMID 29576217, Free PMC Article
    2. Exons encoding the highly conserved part of human glutaminyl-tRNA synthetase. Kaiser E, et al. J Mol Evol, 1992 Jan. PMID 1556743
    3. The human QARS locus: assignment of the human gene for glutaminyl-tRNA synthetase to chromosome 1q32-42. Kunze N, et al. Hum Genet, 1990 Oct. PMID 2227938
    4. The core region of human glutaminyl-tRNA synthetase homologies with the Escherichia coli and yeast enzymes. Thömmes P, et al. Nucleic Acids Res, 1988 Jun 24. PMID 3290852, Free PMC Article
    5. Structural analysis of multifunctional peptide motifs in human bifunctional tRNA synthetase: identification of RNA-binding residues and functional implications for tandem repeats. Jeong EJ, et al. Biochemistry, 2000 Dec 26. PMID 11123902

    See all (257) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. 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.
    3. Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma.
      Title: Prolyl-tRNA synthetase as a novel therapeutic target in multiple myeloma.
    4. 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.
    5. 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.
    6. 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.
    7. five different EPRS mutations were identified.
      Title: Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy.
    8. 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.
    9. 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.
    10. 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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    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)

    Genotypes

    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

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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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

    Homology

    Clone Names

    • DKFZp313B047

    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 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

    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)

    1. 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

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      219968600..220046505 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      219207867..219285874 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P07814.5 GenPept UniProtKB/Swiss-Prot:P07814

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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