EPRS

Bifunctional aminoacyl-tRNA synthetase is an enzyme that in humans is encoded by the EPRS gene.^[1][2]

Gene

Alternative splicing has been observed for this gene, but the full-length nature and biological validity of the variant have not been determined.^[2]

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.^[2]

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.^[3]

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. ^[4]

Interactions

EPRS has been shown to interact with POU2F1,^[5] Heat shock protein 90kDa alpha (cytosolic), member A1^[6] and IARS.^[7]

References

1. ^ 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". J Biol Chem. 266 (3): 1448–55. doi:10.1016/S0021-9258(18)52315-2. PMID 1988429
2. ^ "Entrez Gene: EPRS glutamyl-prolyl-tRNA synthetase"
3. ^ 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". Mol. Cell. 35 (2): 164–80. doi:10.1016/j.molcel.2009.05.028. PMC 2752289. PMID 19647514
4. ^ Witwit, Haydar; Ibanez, Pablo; Zhou, Ruifeng; Jackson, Nathaniel; Escobedo, Ruby; Cubitt, Beatrice; Khafaji, Roaa; Sattler, Rachel Y.; Martinez-Sobrido, Luis; de la Torre, Juan Carlos (2026-02-04). "Prolyl tRNA Synthetase Is Required for Mammarenavirus Multiplication". Viruses. 18 (2): 202. doi:10.3390/v18020202. ISSN 1999-4915
5. ^ 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 Lett.. 424 (1–2): 27–32. Bibcode:1998FEBSL.424...27N. doi:10.1016/S0014-5793(98)00131-8. PMID 9537509. S2CID 872132
6. ^ Kang, J; Kim T; Ko Y G; Rho S B; Park S G; Kim M J; Kwon H J; Kim S (October 2000). "Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases". J. Biol. Chem.. 275 (41): 31682–8. doi:10.1074/jbc.M909965199. ISSN 0021-9258. PMID 10913161
7. ^ Rho, S B; Lee J S; Jeong E J; Kim K S; Kim Y G; Kim S (May 1998). "A multifunctional repeated motif is present in human bifunctional tRNA synthetase". J. Biol. Chem.. 273 (18): 11267–73. doi:10.1074/jbc.273.18.11267. ISSN 0021-9258. PMID 9556618

Further reading

• Kaiser E, Eberhard D, Knippers R (1992). "Exons encoding the highly conserved part of human glutaminyl-tRNA synthetase". J. Mol. Evol.. 34 (1): 45–53. Bibcode:1992JMolE..34...45K. doi:10.1007/BF00163851. PMID 1556743. S2CID 6021527
• Norcum MT (1991). "Structural analysis of the high molecular mass aminoacyl-tRNA synthetase complex. Effects of neutral salts and detergents". J. Biol. Chem.. 266 (23): 15398–405. doi:10.1016/S0021-9258(18)98629-1. PMID 1651330
• Cerini C, Kerjan P, Astier M (1992). "A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase". EMBO J.. 10 (13): 4267–77. doi:10.1002/j.1460-2075.1991.tb05005.x. PMC 453179. PMID 1756734
• Kunze N, Bittler E, Fett R (1990). "The human QARS locus: assignment of the human gene for glutaminyl-tRNA synthetase to chromosome 1q32-42". Hum. Genet.. 85 (5): 527–30. doi:10.1007/BF00194231. PMID 2227938. S2CID 27487450
• Thömmes P, Fett R, Schray B (1988). "The core region of human glutaminyl-tRNA synthetase homologies with the Escherichia coli and yeast enzymes". Nucleic Acids Res.. 16 (12): 5391–406. doi:10.1093/nar/16.12.5391. PMC 336774. PMID 3290852
• Kaiser E, Hu B, Becher S (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): 280–90. doi:10.1006/geno.1994.1059. PMID 8188258
• Hillier LD, Lennon G, Becker M (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res.. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549
• Rho SB, Lee JS, Jeong EJ (1998). "A multifunctional repeated motif is present in human bifunctional tRNA synthetase". J. Biol. Chem.. 273 (18): 11267–73. doi:10.1074/jbc.273.18.11267. PMID 9556618
• Quevillon S, Robinson JC, Berthonneau E (1999). "Macromolecular assemblage of aminoacyl-tRNA synthetases: identification of protein-protein interactions and characterization of a core protein". J. Mol. Biol.. 285 (1): 183–95. doi:10.1006/jmbi.1998.2316. PMID 9878398
• Kang J, Kim T, Ko YG (2000). "Heat shock protein 90 mediates protein-protein interactions between human aminoacyl-tRNA synthetases". J. Biol. Chem.. 275 (41): 31682–8. doi:10.1074/jbc.M909965199. PMID 10913161
• Jeong EJ, Hwang GS, Kim KH (2001). "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): 15775–82. doi:10.1021/bi001393h. PMID 11123902. S2CID 25514243
• Sang Lee J, Gyu Park S, Park H (2002). "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochem. Biophys. Res. Commun.. 291 (1): 158–64. Bibcode:2002BBRC..291..158S. doi:10.1006/bbrc.2002.6398. PMID 11829477
• Strausberg RL, Feingold EA, Grouse LH (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A.. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932
• Bouwmeester T, Bauch A, Ruffner H (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol.. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986
• Beausoleil SA, Jedrychowski M, Schwartz D (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A.. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935
• Sampath P, Mazumder B, Seshadri V (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 (2005). "A novel human tRNA-dihydrouridine synthase involved in pulmonary carcinogenesis". Cancer Res.. 65 (13): 5638–46. doi:10.1158/0008-5472.CAN-05-0600. PMID 15994936
• Beausoleil SA, Villén J, Gerber SA (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol.. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292
• Ewing RM, Chu P, Elisma F (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol.. 3 (1). doi:10.1038/msb4100134. PMC 1847948. PMID 17353931