EPRS1
Description
The EPRS1 (glutamyl-prolyl-tRNA synthetase 1) is a protein-coding gene located on chromosome 1.
EPRS1, also known as bifunctional glutamate/proline--tRNA ligase, bifunctional aminoacyl-tRNA synthetase, Cell proliferation-inducing gene 32 protein, or Glutamatyl-prolyl-tRNA synthetase, is a multifunctional protein. Its primary function is within the aminoacyl-tRNA synthetase multienzyme complex, also referred to as the multisynthetase complex (MSC). Within this complex, it catalyzes the attachment of both L-glutamate and L-proline to their respective tRNAs. This process occurs in two steps: first, the amino acid is activated by ATP, forming a covalent intermediate with AMP. Subsequently, the activated amino acid is transferred to the acceptor end of the tRNA, resulting in the formation of L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro). Upon stimulation by interferon-gamma, EPRS1 undergoes phosphorylation, leading to its dissociation from the MSC. It then participates in the formation of the GAIT complex, which binds to GAIT elements found in the 3'-UTR of various inflammatory mRNAs. This complex inhibits the translation of these mRNAs, enabling interferon-gamma to redirect EPRS1's function from protein synthesis to translation inhibition in specific cellular contexts. Additionally, EPRS1 acts as a downstream effector in the mTORC1 signaling pathway, promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane. This translocation facilitates the uptake of long-chain fatty acids by adipocytes, indicating EPRS1's role in fat metabolism and its indirect influence on lifespan. EPRS1 exists as a homodimer and is part of the MSC, which comprises tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1), the bifunctional ligase for Glu and Pro (EPRS1), and the auxiliary subunits AIMP1/p43, AIMP2/p38, and EEF1E1/p18. The MSC forms a linear complex containing MARS1, EEF1E1, EPRS1, and AIMP2 at its core. EPRS1 interacts with TARS3 and DUS2L. It is also a component of the GAIT complex, composed of EPRS1, RPL13A, and GAPDH. In humans, the GAIT complex assembly appears to be a two-step process, with EPRS1 first associating with SYNCRIP to form a pre-GAIT complex that lacks GAIT element binding. EPRS1, phosphorylated at Ser-999, interacts with SLC27A1, mediating its translocation from the cytoplasm to the plasma membrane, thereby increasing the uptake of long-chain fatty acids.
EPRS1 is a multifunctional protein primarily involved in the aminoacyl-tRNA synthetase multienzyme complex, also known as the multisynthetase complex. In this complex, it catalyzes the attachment of L-glutamate and L-proline to their corresponding tRNAs. This process involves a two-step reaction: first, the amino acid is activated by ATP, forming a covalent intermediate with AMP. Then, the activated amino acid is transferred to the acceptor end of the tRNA, forming L-glutamyl-tRNA(Glu) and L-prolyl-tRNA(Pro). Upon interferon-gamma stimulation, EPRS1 undergoes phosphorylation, causing its dissociation from the aminoacyl-tRNA synthetase complex. It then participates in the formation of the GAIT complex, which binds to GAIT elements found in the 3'-UTR of various inflammatory mRNAs. This complex inhibits the translation of these mRNAs, allowing interferon-gamma to redirect EPRS1's function from protein synthesis to translation inhibition in specific cellular contexts. Furthermore, EPRS1 can act as a downstream effector in the mTORC1 signaling pathway by promoting the translocation of SLC27A1 from the cytoplasm to the plasma membrane. This translocation mediates the uptake of long-chain fatty acids by adipocytes, indicating EPRS1's involvement in fat metabolism and indirect influence on lifespan.
EPRS1 is also known as EARS, EPRS, GLUPRORS, HLD15, PARS, PIG32, QARS, QPRS.
