TFE3

This gene encodes a basic helix-loop-helix domain-containing transcription factor that binds MUE3-type E-box sequences in the promoter of genes. The encoded protein promotes the expression of genes downstream of transforming growth factor beta (TGF-beta) signaling. This gene may be involved in chromosomal translocations in renal cell carcinomas and other cancers, resulting in the production of fusion proteins. Translocation partners include PRCC (papillary renal cell carcinoma), NONO (non-POU domain containing, octamer-binding), and ASPSCR1 (alveolar soft part sarcoma chromosome region, candidate 1), among other genes. Alternative splicing results in multiple transcript variants.

Transcription Factor Binding To IGHM Enhancer 3

Transcription factor that acts as a master regulator of lysosomal biogenesis and immune response (PubMed:2338243, PubMed:29146937, PubMed:30733432, PubMed:31672913).
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 (By similarity).
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:31672913).
Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:31672913).
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).
May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937).

Biological Process adaptive immune responseSource:UniProtKB-KW
Biological Process humoral immune responseSource:UniProtKB
Biological Process negative regulation of cold-induced thermogenesisSource:YuBioLabBy Similarity
Biological Process positive regulation of brown fat cell differentiationSource:UniProtKB
Biological Process positive regulation of cell adhesionSource:UniProtKB1 Publication
Biological Process positive regulation of DNA-templated transcriptionSource:UniProtKB1 Publication
Biological Process positive regulation of transcription by RNA polymerase IISource:UniProtKB1 Publication
Biological Process regulation of osteoclast differentiationSource:InterPro
Biological Process regulation of transcription by RNA polymerase IISource:GO_Central1 Publication

Cytoplasm, cytosol
Nucleus
When nutrients are present, phosphorylation by MTOR prevents nuclear translocation and activity (PubMed:22692423, PubMed:30733432).
Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:22692423, PubMed:30733432).

Sumoylated; does not affect dimerization with MITF.
Phosphorylation by MTOR regulates its subcellular location and activity (PubMed:21209915, PubMed:30733432).
When nutrients are present, phosphorylation by MTOR promotes retention in the cytosol (PubMed:30733432).
Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:30733432).