FEATURES

FAMILY

DESCRIPTION

Also known as NPRL2_HUMAN, NPRL2, TUSC4. 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). 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 GAP activity (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). Within the GATOR complex, component of the GATOR1 subcomplex, made of DEPDC5, NPRL2 and NPRL3 (PubMed:19521502, PubMed:23723238, PubMed:29590090, PubMed:35338845). GATOR1 mediates the strong interaction of the GATOR complex with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD) heterodimers (PubMed:23723238, PubMed:29590090). GATOR1 interacts with GPR155/LYCHOS; interaction takes place in presence of cholesterol and prevents interaction between GATOR1 and KICSTOR (PubMed:36007018). Interacts with PDPK1 (PubMed:18616680).

EXTERNAL LINKS

NPRL2

GATOR1 complex protein NPRL2

NPRL2

Molecular Synopsis