Catalytic component of the GATOR1 complex, a multiprotein complex that functions as an inhibitor of the amino acid-sensing branch of the mTORC1 pathway (PubMed:23723238, PubMed:29590090, PubMed:35338845, PubMed:38006878). 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 (PubMed:23723238, PubMed:29590090, PubMed:35338845). In the presence of abundant amino acids, the GATOR1 complex is ubiquitinated and inhibited by GATOR2 (PubMed:23723238, PubMed:36528027). 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 (PubMed:27173016, PubMed:30651352, PubMed:35338845). ; Suppresses Src-dependent tyrosine phosphorylation and activation of PDPK1 and its downstream signaling (PubMed:18616680). Down-regulates PDPK1 kinase activity by interfering with tyrosine phosphorylation at ‘Tyr-9’, ‘Tyr-373’ and ‘Tyr-376’ residues (PubMed:18616680). May act as a tumor suppressor (PubMed:18616680). Suppresses cell growth and enhances sensitivity to various anticancer drugs (PubMed:18616680).
