EPRS1

EPRS1
Identifiers
Aliases	EPRS1, EARS, GLUPRORS, PARS, QARS, QPRS, PIG32, glutamyl-prolyl-tRNA synthetase, HLD15, glutamyl-prolyl-tRNA synthetase 1, EPRS
External IDs	OMIM: 138295; MGI: 97838; GeneCards: EPRS1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1FYJ, 4HVC, 4K86, 4K87, 4K88, 5A34, 5BMU, 5A1N, 5A5H
Enzyme activity
Gene location (Human)
Chr.	Chromosome 1 (human)
End	220,046,530 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	185,160,557 bp
RNA expression pattern
	Top expressed in
	parotid gland; ; optic nerve; ; secondary oocyte; ; Achilles tendon; ; lateral nuclear group of thalamus; ; ventricular zone; ; tibia; ; islet of Langerhans; ; external globus pallidus; ; Brodmann area 23;
	Top expressed in
	otic placode; ; Rostral migratory stream; ; parotid gland; ; saccule; ; maxillary prominence; ; human fetus; ; mandibular prominence; ; tail of embryo; ; genital tubercle; ; otic vesicle;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	nucleotide binding; protein binding; RNA stem-loop binding; ATP binding; catalytic activity; ligase activity; aminoacyl-tRNA ligase activity; GTPase binding; RNA binding; glutamate-tRNA ligase activity; proline-tRNA ligase activity; zinc ion binding; protein homodimerization activity; metal ion binding; identical protein binding;
Cellular component	membrane; GAIT complex; cytoplasm; aminoacyl-tRNA synthetase multienzyme complex; cytosol; plasma membrane; ribonucleoprotein complex;
Biological process	regulation of translation; tRNA aminoacylation; metabolism; protein biosynthesis; tRNA aminoacylation for protein translation; negative regulation of translation; cellular response to interferon-gamma; glutamyl-tRNA aminoacylation; prolyl-tRNA aminoacylation; cellular response to insulin stimulus; long-chain fatty acid import into cell; protein-containing complex assembly; regulation of long-chain fatty acid import into cell;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	2058
	107508
	ENSG00000136628
	ENSMUSG00000026615
	P07814
	Q8CGC7
	NM_004446
	NM_029735; NM_001357474
	NP_004437
	NP_084011; NP_001344403
	Wikidata
View/Edit Human	View/Edit Mouse

Bifunctional glutamate/proline--tRNA ligase, also called bifunctional aminoacyl-tRNA synthetase, is an enzyme that in humans is encoded by the EPRS1 gene (previously EPRS). This enzyme is located in the cytoplasm, where it attaches the amino acids glutamate and proline to their corresponding transfer RNA (tRNA^Glu and tRNA^Pro) as part of RNA-to-protein translation.

Gene

Alternative splicing has been observed for this gene, but the full-length nature and biological validity of the variant have not been determined.

Function

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.

Phosphorylation of EPRS is reported to be essential for the formation of GAIT (Gamma-interferon Activated Inhibitor of Translation) complex that regulates the translation of multiple genes in monocytes and macrophages.

EPRS1 acts, in human cells, as a proviral factor in mammarenaviruses infection, including LCMV, JUNV, and LASV, and its inhibition using halofuginon compound, a prolyl domain inhibitor, completely abolishes the viral infection by interrupting viral assembly and budding.

Interactions

EPRS has been shown to interact with POU2F1, Heat shock protein 90kDa alpha (cytosolic), member A1 and IARS.

Medical significance

Pathogenic mutations in EPRS1 are associated with a type of disorder of the neural white matter (Leukodystrophy) which is called hypomyelinating leukodystrophy-15 (HLD15).

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000136628 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026615 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Fett R, Knippers R (February 1991). "The primary structure of human glutaminyl-tRNA synthetase. A highly conserved core, amino acid repeat regions, and homologies with translation elongation factors". The Journal of Biological Chemistry. 266 (3): 1448–1455. doi:10.1016/S0021-9258(18)52315-2. PMID 1988429.
1 2 3 4 "Entrez Gene: EPRS glutamyl-prolyl-tRNA synthetase".
↑ "Bifunctional glutamate/proline--tRNA ligase". uniprot.org. UniProt consortium. Retrieved 2026-09-29.
↑ Arif A, Jia J, Mukhopadhyay R, Willard B, Kinter M, Fox PL (July 2009). "Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity". Molecular Cell. 35 (2): 164–180. doi:10.1016/j.molcel.2009.05.028. PMC 2752289. PMID 19647514.
↑ Witwit H, Ibanez PA, Zhou R, Jackson N, Escobedo R, Cubitt B, et al. (February 2026). "Prolyl tRNA Synthetase Is Required for Mammarenavirus Multiplication". Viruses. 18 (2): 202. doi:10.3390/v18020202. PMC 12944994. PMID 41754545.
↑ Nie J, Sakamoto S, Song D, Qu Z, Ota K, Taniguchi T (March 1998). "Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase". FEBS Letters. 424 (1–2): 27–32. Bibcode:1998FEBSL.424...27N. doi:10.1016/S0014-5793(98)00131-8. PMID 9537509. S2CID 872132.
↑ Kang J, Kim T, Ko YG, Rho SB, Park SG, Kim MJ, et al. (October 2000). "Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases". The Journal of Biological Chemistry. 275 (41): 31682–31688. doi:10.1074/jbc.M909965199. PMID 10913161.
↑ Rho SB, Lee JS, Jeong EJ, Kim KS, Kim YG, Kim S (May 1998). "A multifunctional repeated motif is present in human bifunctional tRNA synthetase". The Journal of Biological Chemistry. 273 (18): 11267–11273. doi:10.1074/jbc.273.18.11267. PMID 9556618.
↑ "LEUKODYSTROPHY, HYPOMYELINATING, 15; HLD15". Online Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 2026-09-27.

Kaiser E, Eberhard D, Knippers R (1992). "Exons encoding the highly conserved part of human glutaminyl-tRNA synthetase". Journal of Molecular Evolution. 34 (1): 45–53. Bibcode:1992JMolE..34...45K. doi:10.1007/BF00163851. PMID 1556743. S2CID 6021527.
Norcum MT (August 1991). "Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents". The Journal of Biological Chemistry. 266 (23): 15398–15405. doi:10.1016/S0021-9258(18)98629-1. PMID 1651330.
Cerini C, Kerjan P, Astier M, Gratecos D, Mirande M, Sémériva M (December 1991). "A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase". The EMBO Journal. 10 (13): 4267–4277. doi:10.1002/j.1460-2075.1991.tb05005.x. PMC 453179. PMID 1756734.
Kunze N, Bittler E, Fett R, Schray B, Hameister H, Wiedorn KH, et al. (October 1990). "The human QARS locus: assignment of the human gene for glutaminyl-tRNA synthetase to chromosome 1q32-42". Human Genetics. 85 (5): 527–530. doi:10.1007/BF00194231. PMID 2227938. S2CID 27487450.
Thömmes P, Fett R, Schray B, Kunze N, Knippers R (June 1988). "The core region of human glutaminyl-tRNA synthetase homologies with the Escherichia coli and yeast enzymes". Nucleic Acids Research. 16 (12): 5391–5406. doi:10.1093/nar/16.12.5391. PMC 336774. PMID 3290852.
Kaiser E, Hu B, Becher S, Eberhard D, Schray B, Baack M, et al. (January 1994). "The human EPRS locus (formerly the QARS locus): a gene encoding a class I and a class II aminoacyl-tRNA synthetase". Genomics. 19 (2): 280–290. doi:10.1006/geno.1994.1059. PMID 8188258.
Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S, et al. (September 1996). "Generation and analysis of 280,000 human expressed sequence tags". Genome Research. 6 (9): 807–828. doi:10.1101/gr.6.9.807. PMID 8889549.
Quevillon S, Robinson JC, Berthonneau E, Siatecka M, Mirande M (January 1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". Journal of Molecular Biology. 285 (1): 183–195. doi:10.1006/jmbi.1998.2316. PMID 9878398.
Jeong EJ, Hwang GS, Kim KH, Kim MJ, Kim S, Kim KS (December 2000). "Structural analysis of multifunctional peptide motifs in human bifunctional tRNA synthetase: identification of RNA-binding residues and functional implications for tandem repeats". Biochemistry. 39 (51): 15775–15782. doi:10.1021/bi001393h. PMID 11123902. S2CID 25514243.
Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (February 2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochemical and Biophysical Research Communications. 291 (1): 158–164. Bibcode:2002BBRC..291..158S. doi:10.1006/bbrc.2002.6398. PMID 11829477.
Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
Sampath P, Mazumder B, Seshadri V, Gerber CA, Chavatte L, Kinter M, et al. (October 2004). "Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation". Cell. 119 (2): 195–208. doi:10.1016/j.cell.2004.09.030. PMID 15479637. S2CID 18944876.
Kato T, Daigo Y, Hayama S, Ishikawa N, Yamabuki T, Ito T, et al. (July 2005). "A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis". Cancer Research. 65 (13): 5638–5646. doi:10.1158/0008-5472.CAN-05-0600. PMID 15994936.
Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–1292. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1) 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

This article on a gene on human chromosome 1 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000136628 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026615 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Fett_1991-5] Fett R, Knippers R (February 1991). "The primary structure of human glutaminyl-tRNA synthetase. A highly conserved core, amino acid repeat regions, and homologies with translation elongation factors". The Journal of Biological Chemistry. 266 (3): 1448–1455. doi:10.1016/S0021-9258(18)52315-2. PMID 1988429.

[entrez-6] 1 2 3 4 "Entrez Gene: EPRS glutamyl-prolyl-tRNA synthetase".

[7] "Bifunctional glutamate/proline--tRNA ligase". uniprot.org. UniProt consortium. Retrieved 2026-09-29.

[Arif_2009-8] Arif A, Jia J, Mukhopadhyay R, Willard B, Kinter M, Fox PL (July 2009). "Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity". Molecular Cell. 35 (2): 164–180. doi:10.1016/j.molcel.2009.05.028. PMC 2752289. PMID 19647514.

[9] Witwit H, Ibanez PA, Zhou R, Jackson N, Escobedo R, Cubitt B, et al. (February 2026). "Prolyl tRNA Synthetase Is Required for Mammarenavirus Multiplication". Viruses. 18 (2): 202. doi:10.3390/v18020202. PMC 12944994. PMID 41754545.

[Nie_1998-10] Nie J, Sakamoto S, Song D, Qu Z, Ota K, Taniguchi T (March 1998). "Interaction of Oct-1 and automodification domain of poly(ADP-ribose) synthetase". FEBS Letters. 424 (1–2): 27–32. Bibcode:1998FEBSL.424...27N. doi:10.1016/S0014-5793(98)00131-8. PMID 9537509. S2CID 872132.

[Kang_2000-11] Kang J, Kim T, Ko YG, Rho SB, Park SG, Kim MJ, et al. (October 2000). "Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases". The Journal of Biological Chemistry. 275 (41): 31682–31688. doi:10.1074/jbc.M909965199. PMID 10913161.

[Rho_1998-12] Rho SB, Lee JS, Jeong EJ, Kim KS, Kim YG, Kim S (May 1998). "A multifunctional repeated motif is present in human bifunctional tRNA synthetase". The Journal of Biological Chemistry. 273 (18): 11267–11273. doi:10.1074/jbc.273.18.11267. PMID 9556618.

[13] "LEUKODYSTROPHY, HYPOMYELINATING, 15; HLD15". Online Mendelian Inheritance in Man. Johns Hopkins University. Retrieved 2026-09-27.