EPRS

Official Full Name

glutamyl-prolyl-tRNA synthetase 1

Organism

Homo sapiens

Gene ID

2058

Background

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]

Synonyms

EARS; EPRS; PARS; QARS; QPRS; HLD15; PIG32; GLUPRORS

Bio Chemical Class

Carbon-oxygen ligase

Protein Sequence

MATLSLTVNSGDPPLGALLAVEHVKDDVSISVEEGKENILHVSENVIFTDVNSILRYLARVATTAGLYGSNLMEHTEIDHWLEFSATKLSSCDSFTSTINELNHCLSLRTYLVGNSLSLADLCVWATLKGNAAWQEQLKQKKAPVHVKRWFGFLEAQQAFQSVGTKWDVSTTKARVAPEKKQDVGKFVELPGAEMGKVTVRFPPEASGYLHIGHAKAALLNQHYQVNFKGKLIMRFDDTNPEKEKEDFEKVILEDVAMLHIKPDQFTYTSDHFETIMKYAEKLIQEGKAYVDDTPAEQMKAEREQRIDSKHRKNPIEKNLQMWEEMKKGSQFGQSCCLRAKIDMSSNNGCMRDPTLYRCKIQPHPRTGNKYNVYPTYDFACPIVDSIEGVTHALRTTEYHDRDEQFYWIIEALGIRKPYIWEYSRLNLNNTVLSKRKLTWFVNEGLVDGWDDPRFPTVRGVLRRGMTVEGLKQFIAAQGSSRSVVNMEWDKIWAFNKKVIDPVAPRYVALLKKEVIPVNVPEAQEEMKEVAKHPKNPEVGLKPVWYSPKVFIEGADAETFSEGEMVTFINWGNLNITKIHKNADGKIISLDAKLNLENKDYKKTTKVTWLAETTHALPIPVICVTYEHLITKPVLGKDEDFKQYVNKNSKHEELMLGDPCLKDLKKGDIIQLQRRGFFICDQPYEPVSPYSCKEAPCVLIYIPDGHTKEMPTSGSKEKTKVEATKNETSAPFKERPTPSLNNNCTTSEDSLVLYNRVAVQGDVVRELKAKKAPKEDVDAAVKQLLSLKAEYKEKTGQEYKPGNPPAEIGQNISSNSSASILESKSLYDEVAAQGEVVRKLKAEKSPKAKINEAVECLLSLKAQYKEKTGKEYIPGQPPLSQSSDSSPTRNSEPAGLETPEAKVLFDKVASQGEVVRKLKTEKAPKDQVDIAVQELLQLKAQYKSLIGVEYKPVSATGAEDKDKKKKEKENKSEKQNKPQKQNDGQRKDPSKNQGGGLSSSGAGEGQGPKKQTRLGLEAKKEENLADWYSQVITKSEMIEYHDISGCYILRPWAYAIWEAIKDFFDAEIKKLGVENCYFPMFVSQSALEKEKTHVADFAPEVAWVTRSGKTELAEPIAIRPTSETVMYPAYAKWVQSHRDLPIKLNQWCNVVRWEFKHPQPFLRTREFLWQEGHSAFATMEEAAEEVLQILDLYAQVYEELLAIPVVKGRKTEKEKFAGGDYTTTIEAFISASGRAIQGGTSHHLGQNFSKMFEIVFEDPKIPGEKQFAYQNSWGLTTRTIGVMTMVHGDNMGLVLPPRVACVQVVIIPCGITNALSEEDKEALIAKCNDYRRRLLSVNIRVRADLRDNYSPGWKFNHWELKGVPIRLEVGPRDMKSCQFVAVRRDTGEKLTVAENEAETKLQAILEDIQVTLFTRASEDLKTHMVVANTMEDFQKILDSGKIVQIPFCGEIDCEDWIKKTTARDQDLEPGAPSMGAKSLCIPFKPLCELQPGAKCVCGKNPAKYYTLFGRSY

Open

Disease

Muscular dystrophy

Approved Drug

Clinical Trial Drug

1 +

Discontinued Drug

Cat.No.	Product Name	Price
CSC-DC005011	Panoply™ Human EPRS Knockdown Stable Cell Line	Inquiry
CSC-SC005011	Panoply™ Human EPRS Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD05543Z	Human EPRS adenoviral particles	Inquiry
LV11857L	human EPRS (NM_004446) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH037019	shRNA set against Human EPRS(NM_004446.2)	Inquiry
SHH037037	shRNA set against Mouse Eprs(NM_029735.1)	Inquiry
SHH037001	shRNA set against Rat Eprs(NM_001024238.1)	Inquiry
SHH286637	shRNA set against Human EPRS (NM_004446.2)	Inquiry
SHH286641	shRNA set against Mouse EPRS (NM_029735.1)	Inquiry
SHH286645	shRNA set against Rat EPRS (NM_001024238.1)	Inquiry
SHW000482	shRNA set against Chicken EPRS (NM_001006398)	Inquiry
SHW014288	shRNA set against Danio rerio EPRS (NM_001288652)	Inquiry

Cat.No.	Product Name	Price
CDFH006028	Human EPRS cDNA Clone(NM_004446.2)	Inquiry
CDFR003515	Rat Eprs cDNA Clone(NM_001024238.1)	Inquiry
MiUTR1H-03276	EPRS miRNA 3'UTR clone	Inquiry
MiUTR1M-04443	EPRS miRNA 3'UTR clone	Inquiry
MiUTR1R-01758	EPRS miRNA 3'UTR clone	Inquiry
CDCB161957	Chicken EPRS ORF Clone (NM_001006398)	Inquiry
CDCB175763	Danio rerio EPRS ORF Clone (NM_001288652)	Inquiry
CDCB193527	Rabbit EPRS ORF clone (XM_008268411.1)	Inquiry
CDCR060910	Human EPRS ORF clone (NM_004446.2)	Inquiry
CDCR060912	Mouse Eprs ORF clone (NM_029735.1)	Inquiry
CDCR370566	Rat Eprs ORF Clone(NM_001024238.1)	Inquiry

Detailed Information

Member of the EphB subfamily of Eph receptors, EphB4 is a type I transmembrane receptor. Comprising three primary components—an extracellular ligand-binding domain, a single transmembrane segment, and a cytoplasmic region including a kinase domain—it is similar to other Eph receptors in that Two fibronectin type III repeats, a globular ligand-binding domain, a cysteine-rich area with an epidermal growth factor (EGF)-like motif, and EphB4's extracellular domain comprise These elements mediate high-affinity binding to its main ligand, ephrinB2, which is necessary to initiate signaling pathways linked in cell adhesion, migration, and repulsion.

Bidirectional signaling starts when ephrinB2 interacts with EphB4. EphB4 dimerizes and autophosphorylates on its cytoplasmic tyrosine residues—docking sites for downstream signaling molecules—upon ligand interaction. These comprise phosphatases, kinases, and adaptor proteins controlling different cellular responses including cell shape, motility, and adhesion. Since EphB4 aids in the differentiation of capillary networks into functioning arteries and veins, it is vital for controlling vascular remodeling. Furthermore, crucial for appropriate tissue patterning and function during development are EphB4's mediation of forward signaling in receptor-expressing cells and reverse signaling in ligand-expressing cells.

Figure 1 illustrates the mechanistic actions of EPRS1 released from mesenchymal stem cells (MSCs) in various cellular contexts. Figure 1. Mechanistic actions of EPRS1 released from MSCs. (Lee EY, et al., 2023)

EphB4 in Cancer Pathobiology

Many cancer types, particularly those of the upper aerodigestive tract, increase the EphB4 receptor. EphB4/ephrinB2 interactions reduce cancer in normal cells by blocking Ras-MAPK signaling and hence fostering cell repulsion and segregation. But in tumor cells, EphB4 is frequently overexpressed while its ligand, ephrinB2, is downregulated, therefore upsetting the equilibrium. This disturbance causes contact-dependent signaling to be lost, therefore encouraging tumor growth and metastases.

Furthermore, EphB4 has been linked to control of blood vessel development and permeability, hence fostering angiogenesis inside malignancies. Its high expression combined with other oncogenic signals including those from the ErbB family of receptors can improve cellular proliferation and survival, two fundamental traits of cancer. Though its function is multifaceted, depending on the setting EphB4's interaction with ephrins and downstream signaling events are crucial in both tumor suppression and promotion.

EphB4 as Therapeutic Target

Given EphB4's participation in tumor development, cancer treatment finds an appealing target. With an eye on upsetting the signaling channels driving tumor growth and metastases, recent studies have concentrated on creating small chemical inhibitors that block the EphB4-ephrinB2 interaction. Re-establishing the normal cell adhesion and migration processes disturbed in cancer could help these inhibitors reduce or stop tumor development.

Under investigation a possible immunotherapy target is EphB4. The creation of monoclonal antibodies aimed at EphB4 could help to improve the immunological identification of tumor cells, hence guiding their eradication by the immune system. Particularly in malignancies where EphB4 is overexpressed, EphB4-targeted immunotherapies have demonstrated encouraging outcomes in preclinical models in lowering tumor size and raising survival rates.

Apart from small compounds and antibodies, the function of EphB4 in insulin resistance and metabolic diseases has attracted attention in its possible target for metabolic diseases such as type 2 diabetes. EphB4 has been demonstrated to interact with the insulin receptor (InsR), therefore altering insulin signaling and hence affecting glucose metabolism. Targeting EphB4 in a variety of clinical environments has therapeutic potential highlighted by this dual function in both cancer and metabolic illnesses.

References:

Lee EY, Hwang J, et al. Phosphocode-dependent glutamyl-prolyl-tRNA synthetase 1 signaling in immunity, metabolism, and disease. Exp Mol Med. 2023 Oct;55(10):2116-2126.
Arif A, Yao P, et al. The GAIT translational control system. Wiley Interdiscip Rev RNA. 2018 Mar;9(2):e1441.

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