Anti-FLCN antibody [EPNCIR147]

Target data

Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis (PubMed : 17028174, PubMed : 18663353, PubMed : 21209915, PubMed : 24081491, PubMed : 24095279, PubMed : 31672913, PubMed : 31704029, PubMed : 32612235, PubMed : 34381247, PubMed : 36103527, PubMed : 37079666). GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (PubMed : 17028174, PubMed : 18663353, PubMed : 21209915, PubMed : 24081491, PubMed : 24095279, PubMed : 24448649, PubMed : 31672913, PubMed : 31704029, PubMed : 32612235, PubMed : 36103527, PubMed : 37079666). Activates mTORC1 by acting as a GTPase-activating protein : specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1 (PubMed : 24095279, PubMed : 31672913, PubMed : 31704029, PubMed : 32612235, PubMed : 37079666). The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients (PubMed : 31672913, PubMed : 32612235). Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors TFEB and TFE3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1 (PubMed : 21209915, PubMed : 24081491, PubMed : 31672913, PubMed : 32612235). In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, inactivates mTORC1 and maximizes nuclear translocation of TFEB and TFE3 (PubMed : 31672913). Upon amino acid restimulation, RagA/RRAGA (or RagB/RRAGB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (PubMed : 31672913). Indirectly acts as a positive regulator of Wnt signaling by promoting mTOR-dependent cytoplasmic retention of MiT/TFE factor TFE3 (PubMed : 31272105). Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of TFE3, thereby increasing Wnt signaling (PubMed : 30733432). Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of TFE3 (By similarity). Involved in the control of embryonic stem cells differentiation; together with LAMTOR1 it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent TFE3 inactivation (By similarity). In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia : may act by recruiting STK11/LKB1 to primary cilia for activation of AMPK resided at basal bodies, causing mTORC1 down-regulation (PubMed : 27072130). Together with FNIP1 and/or FNIP2, regulates autophagy : following phosphorylation by ULK1, interacts with GABARAP and promotes autophagy (PubMed : 25126726). Required for starvation-induced perinuclear clustering of lysosomes by promoting association of RILP with its effector RAB34 (PubMed : 27113757). Regulates glycolysis by binding to lactate dehydrogenase LDHA, acting as an uncompetitive inhibitor (PubMed : 34381247).