Catalytic component of the GATOR2 complex, a multiprotein complex that acts as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:26449471, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027, PubMed:36732624). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:26449471, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027, PubMed:36732624). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027, PubMed:36732624). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027, PubMed:36732624). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:26449471, PubMed:26586190, PubMed:27487210). In addition to its role in regulation of the mTORC1 complex, promotes the acidification of lysosomes and facilitates autophagic flux (PubMed:27166823). Within the GATOR2 complex, WDR24 constitutes the catalytic subunit that mediates ‘Lys-6’-linked ubiquitination of NPRL2 (PubMed:36528027, PubMed:36732624).
