Transcription factor EB (Class E basic helix-loop-helix protein 35) (bHLHe35)
1_MASRI 6_ GLRMQ 11_ LMREQ 16_ AQQEE 21_ QRERM 26_ QQQAV 31_ MHYMQ 36_ QQQQQ 41_ QQQQL 46_ GGPPT 51_ PAINT 56_ PVHFQ 61_ SPPPV 66_ PGEVL 71_ KVQSY 76_ LENPT 81_ SYHLQ 86_ QSQHQ 91_ KVREY 96_ LSETY 101_ GNKFA 106_ AHISP 111_ AQGSP 116_ KPPPA 121_ ASPGV 126_ RAGHV 131_ LSSSA 136_ GNSAP 141_ NSPMA 146_ MLHIG 151_ SNPER 156_ ELDDV 161_ IDNIM 166_ RLDDV 171_ LGYIN 176_ PEMQM 181_ PNTLP 186_ LSSSH 191_ LNVYS 196_ SDPQV 201_ TASLV 206_ GVTSS 211_ SCPAD 216_ LTQKR 221_ ELTDA 226_ ESRAL 231_ AKERQ 236_ KKDNH 241_ NLIER 246_ RRRFN 251_ INDRI 256_ KELGM 261_ LIPKA 266_ NDLDV 271_ RWNKG 276_ TILKA 281_ SVDYI 286_ RRMQK 291_ DLQKS 296_ RELEN 301_ HSRRL 306_ EMTNK 311_ QLWLR 316_ IQELE 321_ MQARV 326_ HGLPT 331_ TSPSG 336_ MNMAE 341_ LAQQV 346_ VKQEL 351_ PSEEG 356_ PGEAL 361_ MLGAE 366_ VPDPE 371_ PLPAL 376_ PPQAP 381_ LPLPT 386_ QPPSP 391_ FHHLD 396_ FSHSL 401_ SFGGR 406_ EDEGP 411_ PGYPE 416_ PLAPG 421_ HGSPF 426_ PSLSK 431_ KDLDL 436_ MLLDD 441_ SLLPL 446_ ASDPL 451_ LSTMS 456_ PEASK 461_ ASSRR 466_ SSFSM 471_EEGDV
1: Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:30120233, PubMed:31672913, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823, PubMed:36749723, PubMed:37079666). Specifically recognizes and binds E-box sequences (5'-CANNTG-3'); efficient DNA-binding requires dimerization with itself or with another MiT/TFE family member such as TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Specifically recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, leading to activate their expression, thereby playing a central role in expression of lysosomal genes (PubMed:19556463, PubMed:22692423). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:27278822). In association with TFE3, activates the expression of CD40L in T-cells, thereby playing a role in T-cell-dependent antibody responses in activated CD4(+) T-cells and thymus-dependent humoral immunity (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica: infection promotes itaconate production, leading to alkylation, resulting in nuclear localization and transcription factor activity (PubMed:35662396). Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response (PubMed:35662396). In association with ACSS2, promotes the expression of genes involved in lysosome biogenesis and both autophagy upon glucose deprivation (PubMed:28552616)