Recombinant Human TFE3 protein

Specifications

Form

Liquid

General info

Function

Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed : 2338243, PubMed : 24448649, PubMed : 29146937, PubMed : 30733432, PubMed : 31672913, 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 TFEB or MITF (PubMed : 24448649). Involved in the cellular response to amino acid availability by acting downstream of MTOR : in the presence of nutrients, TFE3 phosphorylation by MTOR promotes its inactivation (PubMed : 24448649, PubMed : 31672913, PubMed : 36608670). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in transcription factor activity (PubMed : 24448649, PubMed : 31672913, PubMed : 36608670). 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 : 24448649). Maintains the pluripotent state of embryonic stem cells by promoting the expression of genes such as ESRRB; mTOR-dependent TFE3 cytosolic retention and inactivation promotes exit from pluripotency (By similarity). Required to maintain the naive pluripotent state of hematopoietic stem cell; mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of hematopoietic stem cell from pluripotency (PubMed : 30733432). TFE3 activity is also involved in the inhibition of neuronal progenitor differentiation (By similarity). Acts as a positive regulator of browning of adipose tissue by promoting expression of target genes; mTOR-dependent phosphorylation promotes cytoplasmic retention of TFE3 and inhibits browning of adipose tissue (By similarity). In association with TFEB, 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 MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer (PubMed : 2338243). It also binds very well to a USF/MLTF site (PubMed : 2338243). Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TSC22D1 at E-boxes in the gene proximal promoter (By similarity). May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed : 29146937).

Sequence similarities

Belongs to the MiT/TFE family.

Post-translational modifications

Sumoylated; does not affect dimerization with MITF.. Phosphorylation ar Ser-47 and Ser-321 by MTOR via non-canonical mTORC1 pathway regulates its stability and subcellular location, respectively (PubMed:21209915, PubMed:24448649, PubMed:30733432, PubMed:36608670). When nutrients are present, phosphorylation by MTOR at Ser-47 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (PubMed:36608670). When nutrients are present, phosphorylation by MTOR at Ser-321 also promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:24448649, PubMed:30733432). Phosphorylation at Ser-47 plays a more critical role than phosphorylation at Ser-321 for TFE3 inactivation (PubMed:36608670). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and transcription factor activity (PubMed:30733432, PubMed:36608670).. Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-47 by MTOR, leading to its degradation by the proteasome.

Subcellular localisation

Nucleus