Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (, ). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (, ). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling . The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 .
Subcellular locations: Lysosome membrane, Cytoplasmic vesicle, Cytoplasm, Cytosol
Localizes in the cytoplasmic vesicles of the endomembrane in association with the TSC-TBC complex . Recruited to lysosomal membranes in a RHEB-dependent process in absence of nutrients . In response to nutrients, the complex dissociates from lysosomal membranes and relocalizes to the cytosol .
Highly expressed in heart, and slightly in kidney, liver and placenta.