Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:16936731, PubMed:29146937). 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:16936731). 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 cytosolic retention and subsequent inactivation (PubMed:27913603). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:27913603). 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 (PubMed:23582324). Required to maintain the naive pluripotent state of hematopoietic stem cell (By similarity). TFE3 activity is also involved in the inhibition of neuronal progenitor differentiation (PubMed:30595499). Acts as a positive regulator of browning of adipose tissue by promoting expression of target genes; mTOR-dependent phosphorylation and cytoplasmic retention of TFE3 inhibits browning of adipose tissue (PubMed:27913603). 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 (PubMed:16936731). Specifically recognizes the MUE3 box, a subset of E-boxes, present in the immunoglobulin enhancer (By similarity). It also binds very well to a USF/MLTF site. May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Homodimer and heterodimer; with TFEB or MITF. Interacts with RRAGC/RagC GDP-bound and RRAGD/RagD GDP-bound (PubMed:30595499). When nutrients are present, phosphorylation by MTOR prevents nuclear translocation and activity (PubMed:23582324, PubMed:27913603). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:23582324, PubMed:27913603). Widely expressed. Sumoylated; does not affect dimerization with MITF. Phosphorylation by MTOR regulates its subcellular location and activity (PubMed:27913603). When nutrients are present, phosphorylation by MTOR promotes retention in the cytosol (PubMed:27913603). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:27913603). Belongs to the MiT/TFE family.