Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

EPRS (P07814) - Overview - Molecular Target Synopsis

Protein


EPRS, Bifunctional glutamate/proline--tRNA ligase
Enzyme Classification 6.1.1.17
UniProt P07814

Also Known as SYEP_HUMAN, EPRS, GLNS, PARS, QARS, QPRS

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 EPRS, 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 EPRS 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). Homodimer (PubMed:24100331, PubMed:23263184). Part of the aminoacyl-tRNA synthetase multienzyme complex, also know as multisynthetase complex (MSC), that is composed of the tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:24312579, PubMed:19131329, PubMed:19289464). Forms a linear complex that contains MARS, EEF1E1, EPRS and AIMP2 that is at the core of the multisubunit complex (PubMed:26472928). Interacts with TARSL2 (PubMed:24312579). Interacts with DUS2L (PubMed:15994936). Component of the GAIT complex which is composed of EPRS, RPL13A and GAPDH. For human, the complex assembly seems to be a two-step process in which EPRS first associates with SYNCRIP to form a pre-GAIT complex which is deficient in GAIT element binding (PubMed:15479637). Interacts (phosphorylated at Ser-999) with SLC27A1; mediates the translocation of SLC27A1 from the cytoplasm to the plasma membrane thereby increasing the uptake of long-chain fatty acids (PubMed:28178239).

5Y6L
A SUBCOMPLEX CRYSTAL STRUCTURE OF HUMAN CYTOSOLIC ASPARTYL-TRNA SYNTHETASE AND HETEROTETRAMERIC GLUTATHIONE TRANSFERASE-HOMOLOGY DOMAINS IN MULTI-TRNA SYNTHETASE COMPLEX
RCSB/PDB
Inspect Structure
See all 3D Structures for EPRS

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: EPRS is active in the following subcellular-locations: cytoplasm, cytosol, membrane.
GO terms: EPRS is active in the following subcellular-locations: aminoacyl-tRNA synthetase multienzyme complex, cytoplasm, cytosol, GAIT complex, membrane, plasma membrane, ribonucleoprotein complex.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project EPRS has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CAKI_1, K_562, RPMI_8226

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: MCF 10A, OCI-M1, AGS

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: NHLF, HSMM, HMEC

(see details)

3D Structures


For EPRS there are:
12 structures (23 chains) solved
5 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

EPRS is solved in complex with the approved drug(s):

ADN/ADENOSINE (4K87_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


EPRS has been screened with 31 compounds (34 bioactivities), 1 compounds have bioactivities that show binding affinity of <= 500nM (2 bioactivities). (see details)