Folliculin (BHD skin lesion fibrofolliculoma protein) (Birt-Hogg-Dube syndrome protein)
1_MNAIV 6_ ALCHF 11_ CELHG 16_ PRTLF 21_ CTEVL 26_ HAPLP 31_ QGDGN 36_ EDSPG 41_ QGEQA 46_ EEEEG 51_ GIQMN 56_ SRMRA 61_ HSPAE 66_ GASVE 71_ SSSPG 76_ PKKSD 81_ MCEGC 86_ RSLAA 91_ GHPGY 96_ ISHDK 101_ ETSIK 106_ YVSHQ 111_ HPSHP 116_ QLFSI 121_ VRQAC 126_ VRSLS 131_ CEVCP 136_ GREGP 141_ IFFGD 146_ EQHGF 151_ VFSHT 156_ FFIKD 161_ SLARG 166_ FQRWY 171_ SIITI 176_ MMDRI 181_ YLINS 186_ WPFLL 191_ GKVRG 196_ IIDEL 201_ QGKAL 206_ KVFEA 211_ EQFGC 216_ PQRAQ 221_ RMNTA 226_ FTPFL 231_ HQRNG 236_ NAARS 241_ LTSLT 246_ SDDNL 251_ WACLH 256_ TSFAW 261_ LLKAC 266_ GSRLT 271_ EKLLE 276_ GAPTE 281_ DTLVQ 286_ MEKLA 291_ DLEEE 296_ SESWD 301_ NSEAE 306_ EEEKA 311_ PVLPE 316_ STEGR 321_ ELTQG 326_ PAESS 331_ SLSGC 336_ GSWQP 341_ RKLPV 346_ FKSLR 351_ HMRQV 356_ LGAPS 361_ FRMLA 366_ WHVLM 371_ GNQVI 376_ WKSRD 381_ VDLVQ 386_ SAFEV 391_ LRTML 396_ PVGCV 401_ RIIPY 406_ SSQYE 411_ EAYRC 416_ NFLGL 421_ SPHVQ 426_ IPPHV 431_ LSSEF 436_ AVIVE 441_ VHAAA 446_ RSTLH 451_ PVGCE 456_ DDQSL 461_ SKYEF 466_ VVTSG 471_ SPVAA 476_ DRVGP 481_ TILNK 486_ IEAAL 491_ TNQNL 496_ SVDVV 501_ DQCLV 506_ CLKEE 511_ WMNKV 516_ KVLFK 521_ FTKVD 526_ SRPKE 531_ DTQKL 536_ LSILG 541_ ASEED 546_ NVKLL 551_ KFWMT 556_ GLSKT 561_ YKSHL 566_ MSTVR 571_SPTAS
1: 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)