Recombinant Human TFEB protein (GST tag N-Terminus)

製品の性状

製品の状態

Liquid

一般的な情報

機能

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).

配列の類似性

Belongs to the MiT/TFE family.

翻訳後修飾

Phosphorylation at Ser-211 by MTOR via non-canonical mTORC1 pathway regulates its subcellular location and activity (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:23401004, PubMed:24081491, PubMed:25720963, PubMed:30120233, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). When nutrients are present, phosphorylation by MTOR promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:23401004, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation by calcineurin PPP3CB and translocation to the nucleus (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32753672). Dephosphorylated by calcineurin PPP3CB in response to lysosomal Ca(2+) release (PubMed:25720963). IRGM promotes dephosphorylation by calcineurin PPP3CB, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (PubMed:32753672). Dephosphorylated by phosphatase PPP3CA following Coxsackievirus B3 infection, leading to nuclear translocation (PubMed:33691586). Exported from the nucleus in a mTORC1-dependent manner in response to nutrient availability (PubMed:30120233).. Alkylated via a non-enzymatic covalent modification (PubMed:35662396). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates Cys-212, preventing association with 14-3-3/YWHA adapters, thereby promoting nuclear translocation and activity (PubMed:35662396).. Sumoylated; does not affect dimerization with MITF.. (Microbial infection) Cleavage by Coxsackievirus B3 protease 3C after site Gln-60. This non-phosphorylated cleavage product retains its ability to interact with TFEB, TFE3 or MITF and presents impaired transcriptional activity, resulting in disruption of lysosomal functions and increased viral infection.

細胞内局在性

Nucleus