TFE3
entrez
7030
canonical
uniprot
P19532
canonical
ensembl
ENSG00000068323
resolver
ensembl
ENSG00000292217
resolver
ensp
ENSP00000314129
resolver
ensp
ENSP00000666236
resolver
genesymbol
TFE3
resolver
genesymbol_syn
BHLHE33
resolver
hgnc
HGNC:11752
resolver
uniprot
A8MZL6
resolver
uniprot
B4DIA5
resolver
uniprot
Q5JU74
resolver
uniprot
Q92757
resolver
uniprot
Q92758
resolver
uniprot
Q99964
resolver
uniprot_entry
B4DIA5_HUMAN
resolver
uniprot_entry
TFE3_HUMAN
resolver
uniprot_sec
A8MZL6
resolver
uniprot_sec
Q5JU74
resolver
uniprot_sec
Q92757
resolver
uniprot_sec
Q92758
resolver
uniprot_sec
Q99964
resolver
amino_acid_sequence
MSHAAEPARDGVEASAEGPRAVFVLLEERRPADSAQLLSLNSLLPESGIVADIELENVLDPDSFYELKSQPLPLRSSLPISLQATPATPATLSASSSAGGSRTPAMSSSSSSRVLLRQQLMRAQAQEQERRERREQAAAAPFPSPAPASPAISVVGVSAGGHTLSRPPPAQVPREVLKVQTHLENPTRYHLQQARRQQVKQYLSTTLGPKLASQALTPPPGPASAQPLPAPEAAHTTGPTGSAPNSPMALLTIGSSSEKEIDDVIDEIISLESSYNDEMLSYLPGGTTGLQLPSTLPVSGNLLDVYSSQGVATPAITVSNSCPAELPNIKREISETEAKALLKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSSDPEMRWNKGTILKASVDYIRKLQKEQQRSKDLESRQRSLEQANRSLQLRIQELELQAQIHGLPVPPTPGLLSLATTSASDSLKPEQLDIEEEGRPGAATFHVGGGPAQNAPHQQPPAPPSDALLDLHFPSDHLGDLGDPFHLGLEDILMEEEEGVVGGLSGGALSPLRAASDPLLSSVSPAVSKASSRRSSFSMEEES
uniprot
proteins
disease_involvement
DISEASE: Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies (MRXSPF) [MIM:301066]: A disorder characterized by severe developmental delay with impaired intellectual development and poor speech, coarse facial dysmorphisms, and Blaschkoid pigmentary mosaicism. Additional clinical features may include epilepsy, orthopedic abnormalities, hypotonia, and growth abnormalities. The disorder affects both males and females. {ECO:0000269|PubMed:30595499, ECO:0000269|PubMed:31833172, ECO:0000269|PubMed:32409512, ECO:0000269|PubMed:36608670}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving TFE3 is found in patients with alveolar soft part sarcoma. Translocation t(X;17)(p11;q25) with ASPSCR1 forms a ASPSCR1-TFE3 fusion protein. {ECO:0000269|PubMed:11358836}.; DISEASE: Renal cell carcinoma Xp11-associated (RCCX1) [MIM:300854]: Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. RCCX1 histology shows both clear cells and papillary architecture, often with abundant psammoma bodies, although variable histologic features have been observed. {ECO:0000269|PubMed:8872474, ECO:0000269|PubMed:8986805}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Chromosomal aberrations involving TFE3 are found in patients with papillary renal cell carcinoma. Translocation t(X;1)(p11.2;q21.2) with PRCC; translocation t(X;1)(p11.2;p34) with PSF; inversion inv(X)(p11.2;q12) that fuses NONO to TFE3. {ECO:0000269|PubMed:8872474, ECO:0000269|PubMed:8986805}.
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q64092, ECO:0000269|PubMed:2338243, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:37079666}.
uniprot
proteins
mass_dalton
61521
uniprot
proteins
mutagenesis
MUTAGEN 47; /note="S->A: Impaired phosphorylation by MTOR, leading to abolished ubiquitination and degradation by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:36608670"; MUTAGEN 112..113; /note="SR->AA: Abolished interaction with Interacts with small GTPases Rag and recruitment to the lysosomal membrane."; /evidence="ECO:0000269|PubMed:24448649"; MUTAGEN 321; /note="S->A: Accumulates in the nucleus due to impaired phosphorylation. Does not affect ubiquitination by the SCF(BTRC) complex."; /evidence="ECO:0000269|PubMed:24448649"; MUTAGEN 356..359; /note="RRRR->AAAA: Abolished localization to the nucleus."; /evidence="ECO:0000269|PubMed:36608670
uniprot
proteins
post_translational_modification
PTM: Sumoylated; does not affect dimerization with MITF. {ECO:0000269|PubMed:15507434}.; PTM: 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). {ECO:0000269|PubMed:21209915, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:36608670}.; 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:0000269|PubMed:36608670}.
uniprot
proteins
protein_family
MiT/TFE family
uniprot
proteins
pubmed
11244503
uniprot
proteins
pubmed
11358836
uniprot
proteins
pubmed
15507434
uniprot
proteins
pubmed
15772651
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
1748288
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21209915
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22692423
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
2338243
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24448649
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
29146937
uniprot
proteins
pubmed
30595499
uniprot
proteins
pubmed
30733432
uniprot
proteins
pubmed
31672913
uniprot
proteins
pubmed
31833172
uniprot
proteins
pubmed
32409512
uniprot
proteins
pubmed
36608670
uniprot
proteins
pubmed
37079666
uniprot
proteins
pubmed
8872474
uniprot
proteins
pubmed
8986805
uniprot
proteins
pubmed
9393982
uniprot
proteins
sequence_length
575
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:21209915, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:37079666}. Nucleus {ECO:0000269|PubMed:21209915, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:37079666}. Lysosome membrane {ECO:0000269|PubMed:24448649}. 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 (PubMed:24448649, PubMed:37079666). Phosphorylation by MTOR prevents nuclear translocation and promotes ubiquitination and degradation (PubMed:22692423, PubMed:30733432, PubMed:36608670, PubMed:37079666). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:22692423, PubMed:30733432, PubMed:37079666). {ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:24448649, ECO:0000269|PubMed:30733432, ECO:0000269|PubMed:36608670, ECO:0000269|PubMed:37079666}.
uniprot
proteins