Anti-FNIP1 antibody [EPNCIR107]

Target data

Binding partner of the GTPase-activating protein FLCN : involved in the cellular response to amino acid availability by regulating the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed : 17028174, PubMed : 18663353, PubMed : 24081491, PubMed : 37079666). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases, leading to activation of the non-canonical mTORC1 signaling (PubMed : 24081491). 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 inactivation of TFEB and TFE3 (PubMed : 37079666). Together with FLCN, regulates autophagy : following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed : 25126726). 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 (PubMed : 27353360, PubMed : 30699359). Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (PubMed : 27353360). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed : 27353360). 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 (PubMed : 32905580).