| Post Translational Modifications | In the presence of abundant amino acids, ubiquitinated at Lys-158 and Lys-357 via 'Lys-6'-linked ubiquitination by the WDR24 component of the GATOR2 complex, thereby inhibiting the GATOR1 complex and promoting mTORC1 activation. Asymmetric dimethylation at Arg-78 by PRMT1 inhibits the GTPase activator activity of the GATOR1 complex and consequently inducing timely mTORC1 activation under methionine-sufficient conditions. |
| Function | Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway. In response to amino acid depletion, the GATOR1 complex has GTPase activating protein (GAP) activity and strongly increases GTP hydrolysis by RagA/RRAGA (or RagB/RRAGB) within heterodimeric Rag complexes, thereby turning them into their inactive GDP-bound form, releasing mTORC1 from lysosomal surface and inhibiting mTORC1 signaling. In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2. Within the GATOR1 complex, NPRL2 constitutes the catalytic subunit that mediates the GTPase activator activity and under methionine-sufficient conditions, the GTPase activator activity is inhibited by PRMT1 through methylation and consequently inducing timely mTORC1 activation. Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling. Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at 'Tyr-9', 'Tyr-373' and 'Tyr-376' residues. May act as a tumor suppressor. Suppresses cell growth and enhances sensitivity to various anticancer drugs. |
| Protein Name | Gator1 Complex Protein Nprl2Gene 21 ProteinG21 ProteinNitrogen Permease Regulator 2-Like ProteinNpr2-Like ProteinTumor Suppressor Candidate 4 |
| Database Links | Reactome: R-HSA-9639288 |
| Cellular Localisation | Lysosome MembraneLocalization To Lysosomes Is Mediated By The Kicstor Complex And Is Amino Acid-Independent |
| Alternative Protein Names | Gator1 Complex Protein Nprl2 proteinGene 21 Protein proteinG21 Protein proteinNitrogen Permease Regulator 2-Like Protein proteinNpr2-Like Protein proteinTumor Suppressor Candidate 4 proteinNPRL2 proteinTUSC4 protein |
Information sourced from Uniprot.org
