Tfe3
entrez
209446
canonical
uniprot
Q64092
canonical
ensembl
ENSMUSG00000000134
resolver
ensp
ENSMUSP00000076864
resolver
ensp
ENSMUSP00000078498
resolver
ensp
ENSMUSP00000099219
resolver
ensp
ENSMUSP00000111341
resolver
ensp
ENSMUSP00000111342
resolver
ensp
ENSMUSP00000111343
resolver
ensp
ENSMUSP00000134125
resolver
enst
ENSMUST00000077680
resolver
enst
ENSMUST00000079542
resolver
genesymbol
Tfe3
resolver
genesymbol_syn
Tcfe3
resolver
uniprot
A2AEW0
resolver
uniprot
A2AEW1
resolver
uniprot
A2AEW3
resolver
uniprot
A2AEW4
resolver
uniprot
Q3U1L5
resolver
uniprot
Q3U8H0
resolver
uniprot
Q3UMV4
resolver
uniprot
Q3UT52
resolver
uniprot
Q7TNC1
resolver
uniprot
Q8BN29
resolver
uniprot
Q8K420
resolver
uniprot_entry
A2AEW0_MOUSE
resolver
uniprot_entry
A2AEW1_MOUSE
resolver
uniprot_entry
Q3U1L5_MOUSE
resolver
uniprot_entry
Q8K420_MOUSE
resolver
uniprot_entry
TFE3_MOUSE
resolver
uniprot_sec
A2AEW3
resolver
uniprot_sec
A2AEW4
resolver
uniprot_sec
Q3U8H0
resolver
uniprot_sec
Q3UMV4
resolver
uniprot_sec
Q3UT52
resolver
uniprot_sec
Q7TNC1
resolver
uniprot_sec
Q8BN29
resolver
amino_acid_sequence
MSHAAEPARDAVEASAEGPRAVFLLLEERRPAESAQLLSLNSLLPESGIVADIELENILDPDSFYELKSQPLFLRSSLPISLQATPTTPATLSASSSAGGSRTPAMSSSSSRVLLRQQLMRAQAQEQERRERREQAAAAPFPSPAPASPAISVIGVSAGGHTLSRPPPAQVPREVLKVQTHLENPTRYHLQQARRQQVKQYLSTTLGPKLASQALTPPPGPSSAQPLPAPETAHATGPTGSAPNSPMALLTIGSSSEKEIDDVIDEIISLESSYNDEMLSYLPGGTAGLQLPSTLPVSGNLLDVYSSQGVATPAITVSNSCPAELPNIKREISETEAKALLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPEMRWNKGTILKASVDYIRKLQKEQQRSKDLESRQRSLEQANRSLQLRIQELELQAQIHGLPVPPNPGLLSLTTSSVSDSLKPEQLDIEEEGRPSTTFHVSGGPAQNAPPQQPPAPPSDALLDLHFPSDHLGDLGDPFHLGLEDILMEEEGMVGGLSGGALSPLRAASDPLLSSVSPAVSKASSRRSSFSMEEES
uniprot
proteins
function
FUNCTION: 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 inactivation (PubMed:27913603). Upon starvation or lysosomal stress, inhibition of MTOR induces TFE3 dephosphorylation, resulting in transcription factor activity (PubMed:27913603). 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 (By similarity). 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; mTOR-dependent cytoplasmic retention of TFE3 promotes the exit of hematopoietic stem cell from pluripotency (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 promotes cytoplasmic retention of TFE3 and 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 (By similarity). Promotes TGF-beta-induced transcription of COL1A2; via its interaction with TSC22D1 at E-boxes in the gene proximal promoter (PubMed:20713358). May regulate lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). {ECO:0000250|UniProtKB:P19532, ECO:0000269|PubMed:16936731, ECO:0000269|PubMed:20713358, ECO:0000269|PubMed:23582324, ECO:0000269|PubMed:27913603, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30595499}.
uniprot
proteins
mass_dalton
61536
uniprot
proteins
mutagenesis
MUTAGEN 320; /note="S->A: Impaired phosphorylation by MTOR, leading to constitutive nuclear localization."; /evidence="ECO:0000269|PubMed:27913603
uniprot
proteins
post_translational_modification
PTM: Sumoylated; does not affect dimerization with MITF. {ECO:0000250|UniProtKB:P19532}.; PTM: Phosphorylation ar Ser-47 and Ser-320 by MTOR via non-canonical mTORC1 pathway regulates its stability and subcellular location, respectively (PubMed:27913603). When nutrients are present, phosphorylation by MTOR at Ser-47 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (By similarity). When nutrients are present, phosphorylation by MTOR at Ser-320 also promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:27913603). Phosphorylation at Ser-47 plays a more critical role than phosphorylation at Ser-320 for TFE3 inactivation (By similarity). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and transcription factor activity (PubMed:27913603). {ECO:0000250|UniProtKB:P19532, ECO:0000269|PubMed:27913603}.; PTM: Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-47 by MTOR, leading to its degradation by the proteasome. {ECO:0000250|UniProtKB:P19532}.
uniprot
proteins
protein_family
MiT/TFE family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16936731
uniprot
proteins
pubmed
1732746
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20713358
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21209915
uniprot
proteins
pubmed
23582324
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
27913603
uniprot
proteins
pubmed
29146937
uniprot
proteins
pubmed
30595499
uniprot
proteins
sequence_length
572
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23582324, ECO:0000269|PubMed:27913603, ECO:0000305|PubMed:21209915}. Nucleus {ECO:0000269|PubMed:21209915, ECO:0000269|PubMed:23582324, ECO:0000269|PubMed:27913603}. Lysosome membrane {ECO:0000250|UniProtKB:P19532}. Note=When nutrients are present, recruited to the lysosomal membrane via association with GDP-bound RagC/RRAGC (or RagD/RRAGD): it is then phosphorylated by MTOR (By similarity). Phosphorylation by MTOR prevents nuclear translocation and promotes ubiquitination and degradation (PubMed:23582324, PubMed:27913603). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:23582324, PubMed:27913603). {ECO:0000250|UniProtKB:P19532, ECO:0000269|PubMed:23582324, ECO:0000269|PubMed:27913603}.
uniprot
proteins