Protein Variants | Comment | Organism |
---|---|---|
F50A/Y52A | site-directed mutagenesis, the leucine-binding deficient LRS mutant also activates Vps34, but to a lesser degree and in a leucine-independent manner | Homo sapiens |
additional information | enzyme knockout by shRNA and iRNA | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-leucine + tRNALeu | Homo sapiens | - |
AMP + diphosphate + L-leucyl-tRNALeu | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q9P2J5 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HEK-293 cell | - |
Homo sapiens | - |
MEF cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + L-leucine + tRNALeu | - |
Homo sapiens | AMP + diphosphate + L-leucyl-tRNALeu | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Leucyl-tRNA synthetase | - |
Homo sapiens |
LRS | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
malfunction | knockdown of LRS in HEK-293 cells results in impaired leucine-stimulated S6K1 phosphorylation, total amino acid stimulation of pS6K1 is also significantly reduced. Knockdown of LRS decreasesVps34 activity induced by leucine or total amino acids. Knockdown of LRS does not affect the protein levels of mTOR, raptor, Vps34, and Rag GTPases | Homo sapiens |
metabolism | mTORC1 lysosomal translocation and activation in response to amino acids requires the GTP-bound form of RagA or B as well as the GDP-bound form of RagC or D. The Ragulator complex and the GATOR1 complex act as GEF (guanine nucleotide exchange factor) and GAP (GTPase activating protein) for RagA/B, respectively. Role of LRS as a leucine sensor upstream of TORC1. Two other tRNA synthetases, IRS (isoleucyl-tRNA synthetase) and EPRS (glutamyl-prolyl-tRNA synthetase), are both in the multi-tRNA synthetase complex together with enzyme LRS, but both have no effect on leucine-stimulated Vps34 activity. LRS directly regulates Vps34 activity | Homo sapiens |
physiological function | leucyl-tRNA synthetase (LRS) is a leucine sensor for the activation of Vps34-PLD1 upstream of mTORC1. LRS binds to RagD-GTP, and forms a LRS-RagD complex, which translocates mTORC1 from the cytosol to the lysosome surface for subsequent activation of the mTORC1 signalling pathway. LRS is necessary for amino acid-induced Vps34 activation, cellular phosphatidylinositol-3-phosphate level increase, PLD1 activation, and PLD1 lysosomal translocation. Leucine binding but not tRNA charging activity of LRS is required for this regulation. LRS directly interacts with Vps34 in a non-autophagic complex, and activates Vps34 kinase activity in a leucine-dependent manner. Vps34 and PLD1 are required to mediate LRS activation of mTORC1. Only non-autophagic Vps34 complexes are involved in amino acid signaling to mTOR. LRS is necessary for amino acid activation of PLD1. Overexpression of LRS enhanced amino acid activation of S6K1 | Homo sapiens |