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Literature summary extracted from

  • Yoon, M.S.; Son, K.; Arauz, E.; Han, J.M.; Kim, S.; Chen, J.
    Leucyl-tRNA synthetase activates Vps34 in amino acid-sensing mTORC1 signaling (2016), Cell Rep., 16, 1510-1517 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
6.1.1.4 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
6.1.1.4 additional information enzyme knockout by shRNA and iRNA Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
6.1.1.4 cytosol
-
 Homo sapiens 5829
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.1.1.4 Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.1.1.4 ATP + L-leucine + tRNALeu Homo sapiens
-
 AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.1.1.4 Homo sapiens Q9P2J5
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.1.1.4 HEK-293 cell
-
 Homo sapiens
-
6.1.1.4 MEF cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.1.1.4 ATP + L-leucine + tRNALeu
-
 Homo sapiens AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Synonyms

EC Number Synonyms Comment Organism
6.1.1.4 Leucyl-tRNA synthetase
-
 Homo sapiens
6.1.1.4 LRS
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
6.1.1.4 ATP
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
6.1.1.4 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
6.1.1.4 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
6.1.1.4 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