Tfeb
entrez
21425
canonical
uniprot
Q9R210
canonical
ensembl
ENSMUSG00000023990
resolver
ensp
ENSMUSP00000024786
resolver
ensp
ENSMUSP00000084151
resolver
ensp
ENSMUSP00000108913
resolver
ensp
ENSMUSP00000223384
resolver
ensp
ENSMUSP00000223391
resolver
ensp
ENSMUSP00000338933
resolver
enst
ENSMUST00000024786
resolver
enst
ENSMUST00000086932
resolver
enst
ENSMUST00000113288
resolver
genesymbol
Tfeb
resolver
genesymbol_syn
Tcfeb
resolver
uniprot
F6UP91
resolver
uniprot
Q3UKG7
resolver
uniprot
Q6P203
resolver
uniprot
Q8C5F1
resolver
uniprot_entry
F6UP91_MOUSE
resolver
uniprot_entry
Q3UKG7_MOUSE
resolver
uniprot_entry
Q6P203_MOUSE
resolver
uniprot_entry
Q8C5F1_MOUSE
resolver
uniprot_entry
TFEB_MOUSE
resolver
amino_acid_sequence
MASRIGLRMQLMREQAQQEEQRERMQQQAVMHYMQQQQQQQQQLGGPPTPAINTPVHFQSPPPVPGEVLKVQSYLENPTSYHLQQSQHQKVREYLSETYGNKFAAHVSPAQGSPKPAPAASPGVRAGHVLSTSAGNSAPNSPMAMLHISSNPEKEFDDVIDNIMRLDSVLGYINPEMQMPNTLPLSSSHLNVYSGDPQVTASMVGVTSSSCPADLTQKRELTDAESRALAKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRRLEMTNKQLWLRIQELEMQARVHGLPTTSPSGVNMAELAQQVVKQELPSEDGPGEALMLGPEVPEPEQMPALPPQAPLPSAAQPQSPFHHLDFSHGLSFGGGGDEGPTGYPDTLGTEHGSPFPNLSKKDLDLMLLDDSLLPLASDPLFSTMSPEASKASSRRSSFSMEEGDVL
uniprot
proteins
function
FUNCTION: Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response (PubMed:16936731, PubMed:22343943, PubMed:27278822, PubMed:35662396). 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 TFE3 or MITF (PubMed:16936731, PubMed:27278822). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, TFEB phosphorylation by MTOR promotes its cytosolic retention and subsequent inactivation (PubMed:35662396). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (By similarity). 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). Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1 (PubMed:29146937). Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy (PubMed:27278822). In association with TFE3, 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 gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (By similarity). Plays a role in the signal transduction processes required for normal vascularization of the placenta (PubMed:9806910). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica (PubMed:24882217, PubMed:27184844, PubMed:35662396). Infection promotes itaconate production, leading to alkylation, resulting in nuclear localization and transcription factor activity (PubMed:35662396). Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response (PubMed:35662396). In association with ACSS2, promotes the expression of genes involved in lysosome biogenesis and both autophagy upon glucose deprivation (By similarity). {ECO:0000250|UniProtKB:P19484, ECO:0000269|PubMed:16936731, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:24882217, ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:9806910}.
uniprot
proteins
mass_dalton
52614
uniprot
proteins
mutagenesis
MUTAGEN 211; /note="C->S: Abolished alkylation in knockin mice. Mice display elevated susceptibility to S.typhimurium infection."; /evidence="ECO:0000269|PubMed:35662396
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-210 by MTOR via non-canonical mTORC1 pathway regulates its subcellular location and activity (By similarity). When nutrients are present, phosphorylation by MTOR promotes association with 14-3-3/YWHA adapters and retention in the cytosol (By similarity). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation by calcineurin PPP3CB and translocation to the nucleus (By similarity). Dephosphorylated by calcineurin PPP3CB in response to lysosomal Ca(2+) release (By similarity). Irgm1 promotes dephosphorylation by calcineurin PPP3CB, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (By similarity). Exported from the nucleus in a mTORC1-dependent manner in response to nutrient availability (By similarity). {ECO:0000250|UniProtKB:P19484}.; PTM: Alkylated via a non-enzymatic covalent modification (PubMed:35662396). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates Cys-211, preventing association with 14-3-3/YWHA adapters, thereby promoting nuclear translocation and activity (PubMed:35662396). {ECO:0000269|PubMed:35662396}.; PTM: Sumoylated; does not affect dimerization with MITF. {ECO:0000250|UniProtKB:P19484}.
uniprot
proteins
protein_family
MiT/TFE family
uniprot
proteins
pubmed
10036191
uniprot
proteins
pubmed
16936731
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19144319
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22343943
uniprot
proteins
pubmed
24882217
uniprot
proteins
pubmed
27184844
uniprot
proteins
pubmed
27278822
uniprot
proteins
pubmed
29146937
uniprot
proteins
pubmed
32612235
uniprot
proteins
pubmed
35662396
uniprot
proteins
pubmed
9806910
uniprot
proteins
sequence_length
475
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:32612235}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P19484}. Lysosome membrane {ECO:0000250|UniProtKB:P19484}. Note=Mainly present in the cytoplasm (By similarity). 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 activity by promoting interaction with 14-3-3 proteins, such as YWHAZ (By similarity). Under aberrant lysosomal storage conditions, it translocates from the cytoplasm to the nucleus (By similarity). The translocation to the nucleus is regulated by ATP13A2 (PubMed:27278822). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (By similarity). Exported from the nucleus in response to nutrient availability (By similarity). In macrophages, translocates into the nucleus upon live S.enterica infection (By similarity). {ECO:0000250|UniProtKB:P19484, ECO:0000269|PubMed:27278822}.
uniprot
proteins