Recombinant Human TFEB protein (GST tag N-Terminus)

Specifications

Form

Liquid

General info

Function

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).

Sequence similarities

Belongs to the MiT/TFE family.

Post-translational modifications

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.

Subcellular localisation

Nucleus