Bifunctional glutamate/proline--tRNA ligase (EPRS)
The protein contains 1512 amino acids for an estimated molecular weight of 170591 Da.
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 EPRS1, 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 EPRS1 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). (updated: Feb. 26, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Cellular response to insulin stimulus
Cellular response to interferon-gamma
Gene expression
Glutamyl-tRNA aminoacylation
Long-chain fatty acid import into cell
Negative regulation of translation
Prolyl-tRNA aminoacylation
Protein complex assembly
Protein-containing complex assembly
Regulation of long-chain fatty acid import into cell
TRNA aminoacylation for protein translation
The reference OMIM entry for this protein is 138295
Glutamyl-prolyl-trna synthetase; eprs
Glu-pro-trna synthetase; gluprors
Prolyl-trna synthetase; pars
DESCRIPTION
Aminoacyl-tRNA synthetases are enzymes that charge tRNAs with their cognate amino acids. This is an essential first step in the translation of the genetic message because, together with codon-anticodon recognition, the specificity of this reaction determines the fidelity of mRNA translation. At least 1 synthetase exists in the cytoplasm for each amino acid (Kunze et al., 1990). In higher eukaryotes, 9 aminoacyl-tRNA synthetases are associated within a multienzyme complex that is composed of 11 polypeptides with molecular masses ranging from 18 to 150 kD. EPRS is a multifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species (Cerini et al., 1991).CLONING
Cerini et al. (1991) cloned a cDNA from Drosophila encoding the largest polypeptide of the aminoacyl-tRNA synthetase complex. They demonstrated that the corresponding protein is a multifunctional aminoacyl-tRNA synthetase specifying 2 distinct synthetase activities. The N- and C-terminal domains, when expressed separately in Escherichia coli, were found to catalyze the aminoacylation of glutamic acid and proline tRNA species, respectively. In prokaryotes, these 2 aminoacyl-tRNA synthetases are encoded by distinct genes. The emergence of a multifunctional synthetase by a gene fusion event seems to be a specific, but general attribute of all higher eukaryotic cells. This type of structural organization, in relation to the occurrence of multisynthetase complexes, could be a mechanism to integrate several catalytic domains within the same particle. In humans, as in Drosophila, glutamyl-tRNA synthetase (GluRS) and prolyl-tRNA synthetase (ProRS) activities are contained within a single polypeptide chain, designated EPRS, even though these enzymes belong to different classes and are thought to have evolved along independent evolutionary pathways (Kaiser et al., 1994). From the open reading frame found in cDNA clones, Fett and Knippers (1991) concluded that the EPRS enzyme comprises 1,440 amino acids. Jia et al. (2008) stated that human EPRS is a 172-kD protein containing an N-terminal elongation factor-1B-gamma (EEF1G; 130593)-like domain, followed by an ERS catalytic domain, a 300-amino acid linker region, and a C-terminal PRS catalytic domain. The linker region contains 3 tandem WHEP domains, which are 50-amino acid helix-turn-helix structures found in other aminoacyl-tRNA synthases. Lo et al. (2014) reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. Lo et al. (2014) identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 1 catalytic domain-retained splice variant for GluProRS.GENE FUNCTION
Sampath et al. (2004) showed that EPRS has a regulated, noncanonical activity that blocks synthesis o ... More on the omim web site
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 26, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 5, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138295 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed