功能
Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 . In low-amino acid conditions , component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes , which inhibits the GTPase-activating activity of FLCN , thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3 (By similarity) . Upon amino acid restimulation , disassembly of the LFC complex liberates the GTPase-activating activity of FLCN , leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity) . Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases . Together with FLCN , regulates autophagy: following phosphorylation by ULK1 , interacts with GABARAP and promotes autophagy . In addition to its role in mTORC1 signaling , also acts as a co-chaperone of HSP90AA1/Hsp90: following gradual phosphorylation by CK2 , inhibits the ATPase activity of HSP90AA1/Hsp90 , leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90 . Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 . Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1 , thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins . Also acts as a core component of the reductive stress response by inhibiting activation of mitochondria in normal conditions: in response to reductive stress , the conserved Cys degron is reduced , leading to recognition and polyubiquitylation by the CRL2 (FEM1B) complex , followed by proteasomal (By similarity) . Required for B-cell development (By similarity) .
