TFEB
entrez
7942
canonical
uniprot
P19484
canonical
ensembl
ENSG00000112561
resolver
ensp
ENSP00000230323
resolver
ensp
ENSP00000351742
resolver
ensp
ENSP00000362124
resolver
ensp
ENSP00000383998
resolver
ensp
ENSP00000384203
resolver
ensp
ENSP00000400276
resolver
ensp
ENSP00000503069
resolver
ensp
ENSP00000611072
resolver
enst
ENST00000358871
resolver
genesymbol
TFEB
resolver
genesymbol_syn
BHLHE35
resolver
hgnc
HGNC:11753
resolver
uniprot
B0QYS6
resolver
uniprot
Q709B3
resolver
uniprot
Q7Z6P9
resolver
uniprot
Q9BRJ5
resolver
uniprot
Q9UJD8
resolver
uniprot_entry
B0QYS6_HUMAN
resolver
uniprot_entry
TFEB_HUMAN
resolver
uniprot_sec
Q709B3
resolver
uniprot_sec
Q7Z6P9
resolver
uniprot_sec
Q9BRJ5
resolver
uniprot_sec
Q9UJD8
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by eltrombopag drug, which binds to the bHLH domain and disrupts DNA-binding. {ECO:0000269|PubMed:36749723}.
uniprot
proteins
amino_acid_sequence
MASRIGLRMQLMREQAQQEEQRERMQQQAVMHYMQQQQQQQQQQLGGPPTPAINTPVHFQSPPPVPGEVLKVQSYLENPTSYHLQQSQHQKVREYLSETYGNKFAAHISPAQGSPKPPPAASPGVRAGHVLSSSAGNSAPNSPMAMLHIGSNPERELDDVIDNIMRLDDVLGYINPEMQMPNTLPLSSSHLNVYSSDPQVTASLVGVTSSSCPADLTQKRELTDAESRALAKERQKKDNHNLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELENHSRRLEMTNKQLWLRIQELEMQARVHGLPTTSPSGMNMAELAQQVVKQELPSEEGPGEALMLGAEVPDPEPLPALPPQAPLPLPTQPPSPFHHLDFSHSLSFGGREDEGPPGYPEPLAPGHGSPFPSLSKKDLDLMLLDDSLLPLASDPLLSTMSPEASKASSRRSSFSMEEGDVL
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:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:30120233, PubMed:31672913, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823, PubMed:36749723, 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 TFE3 or MITF (PubMed:1748288, PubMed:19556463, PubMed:29146937). 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:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). 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:19556463, PubMed:22692423). 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:21617040, PubMed:22576015, PubMed:23434374, 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 (By similarity). Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer (PubMed:2115126). Plays a role in the signal transduction processes required for normal vascularization of the placenta (By similarity). Involved in the immune response to infection by the bacteria S.aureus, S.typhimurium or S.enterica: 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 (PubMed:28552616). {ECO:0000250|UniProtKB:Q9R210, ECO:0000269|PubMed:1748288, ECO:0000269|PubMed:19556463, ECO:0000269|PubMed:2115126, ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:29146937, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:31672913, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:36749723, ECO:0000269|PubMed:37079666}.
uniprot
proteins
mass_dalton
52865
uniprot
proteins
mutagenesis
MUTAGEN 3..4; /note="SR->AA: Abolished recruitment to lysosomal membrane in response to nutrients, leading to constitutive nuclear localization."; /evidence="ECO:0000269|PubMed:23401004"; MUTAGEN 10..11; /note="QL->AA: Abolished recruitment to lysosomal membrane in response to nutrients, leading to constitutive nuclear localization."; /evidence="ECO:0000269|PubMed:23401004"; MUTAGEN 19..20; /note="EE->AA: Does not affect recruitment to lysosomal membrane in response to nutrients."; /evidence="ECO:0000269|PubMed:23401004"; MUTAGEN 22..24; /note="RER->AAA: Does not affect recruitment to lysosomal membrane in response to nutrients."; /evidence="ECO:0000269|PubMed:23401004"; MUTAGEN 60..61; /note="QS->LP: Impaired cleavage by Coxsackievirus B3 protease 3C."; /evidence="ECO:0000269|PubMed:33691586"; MUTAGEN 138; /note="S->A: Impaired nuclear export in response to nutrient availability."; /evidence="ECO:0000269|PubMed:30120233"; MUTAGEN 142; /note="S->A: Impaired phosphorylation by MTOR, leading to constitutive nuclear localization and transcription factor activity. Impaired nuclear export in response to nutrient availability."; /evidence="ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:30120233"; MUTAGEN 142; /note="S->D: Mimics phosphorylation status; abolished translocation to the nucleus in response to starvation."; /evidence="ECO:0000269|PubMed:21617040"; MUTAGEN 144..149; /note="MAMLHI->AAMAHA: Abolished nuclear export in response to nutrient availability."; /evidence="ECO:0000269|PubMed:30120233"; MUTAGEN 209; /note="S->A: Does not affect interaction with 14-3-3/YWHA and subcellular localization."; /evidence="ECO:0000269|PubMed:22576015"; MUTAGEN 210; /note="S->A: Does not affect interaction with 14-3-3/YWHA and subcellular localization."; /evidence="ECO:0000269|PubMed:22576015"; MUTAGEN 211; /note="S->A: Impaired phosphorylation by MTOR, leading to reduced interaction with 14-3-3/YWHA and constitutive nuclear localization. Does not affect nuclear export in response to nutrient availability."; /evidence="ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:36697823"; MUTAGEN 211; /note="S->D: Mimics phosphorylation; leading to increased interaction with 14-3-3/YWHA and impaired nuclear localization."; /evidence="ECO:0000269|PubMed:35662396"; MUTAGEN 212; /note="C->S: Abolished alkylation, abolishing ability to prevent association with 14-3-3/YWHA adapters."; /evidence="ECO:0000269|PubMed:35662396"; MUTAGEN 245..247; /note="RRR->AAA: Abolished nuclear localization upon mTORC1 inactivation."; /evidence="ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:36697823"; MUTAGEN 248..254; /note="RFNINDR->AFNINDA: In MutCom_1 mutant; abolished ability to bind eltrombopag drug; when associated with 271-A--A-274."; /evidence="ECO:0000269|PubMed:36749723"; MUTAGEN 256..264; /note="KELGMLIPK->AELGMLIPA: In MutCom_2 mutant; does not affect ability to bind eltrombopag drug."; /evidence="ECO:0000269|PubMed:36749723"; MUTAGEN 271..274; /note="RWNK->AWNA: In MutCom_1 mutant; abolished ability to bind eltrombopag drug; when associated with 248-A--A-254."; /evidence="ECO:0000269|PubMed:36749723"; MUTAGEN 271; /note="R->A: Abolished ability to bind eltrombopag drug."; /evidence="ECO:0000269|PubMed:36749723"; MUTAGEN 279..290; /note="KASVDYIRRMQK->AASVDYIAAMQA: In MutCom_3 mutant; does not affect ability to bind eltrombopag drug."; /evidence="ECO:0000269|PubMed:36749723"; MUTAGEN 296..315; /note="RELENHSRRLEMTNKQLWLR->AELENHSAALEMTNAQLWLA: In MutCom_4 mutant; does not affect ability to bind eltrombopag drug."; /evidence="ECO:0000269|PubMed:36749723"; MUTAGEN 331..332; /note="TS->AA: Does not affect interaction with 14-3-3/YWHA and subcellular localization."; /evidence="ECO:0000269|PubMed:22576015"; MUTAGEN 332; /note="S->A: Does not affect nuclear localization."; /evidence="ECO:0000269|PubMed:21617040"; MUTAGEN 423; /note="S->A: Does not affect nuclear localization."; /evidence="ECO:0000269|PubMed:21617040
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Ser-211 by MTOR via non-canonical mTORC1 pathway regulates its subcellular location and activity (PubMed:21617040, PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:23401004, PubMed:24081491, PubMed:25720963, PubMed:30120233, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823). When nutrients are present, phosphorylation by MTOR promotes association with 14-3-3/YWHA adapters and retention in the cytosol (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:23401004, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396). Inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation by calcineurin PPP3CB and translocation to the nucleus (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:25720963, PubMed:32753672). Dephosphorylated by calcineurin PPP3CB in response to lysosomal Ca(2+) release (PubMed:25720963). IRGM promotes dephosphorylation by calcineurin PPP3CB, resulting in TFEB nuclear translocation and stimulation of lysosomal biogenesis (PubMed:32753672). Dephosphorylated by phosphatase PPP3CA following Coxsackievirus B3 infection, leading to nuclear translocation (PubMed:33691586). Exported from the nucleus in a mTORC1-dependent manner in response to nutrient availability (PubMed:30120233). {ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:33691586, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823}.; PTM: Alkylated via a non-enzymatic covalent modification (PubMed:35662396). Itaconate, an anti-inflammatory metabolite generated in response to lipopolysaccharide, alkylates Cys-212, 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:0000269|PubMed:15507434}.; PTM: (Microbial infection) Cleavage by Coxsackievirus B3 protease 3C after site Gln-60. This non-phosphorylated cleavage product retains its ability to interact with TFEB, TFE3 or MITF and presents impaired transcriptional activity, resulting in disruption of lysosomal functions and increased viral infection. {ECO:0000269|PubMed:33691586}.
uniprot
proteins
protein_family
MiT/TFE family
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
15118077
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15507434
uniprot
proteins
pubmed
1748288
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19556463
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
2115126
uniprot
proteins
pubmed
21617040
uniprot
proteins
pubmed
22343943
uniprot
proteins
pubmed
22576015
uniprot
proteins
pubmed
22692423
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23401004
uniprot
proteins
pubmed
23434374
uniprot
proteins
pubmed
24081491
uniprot
proteins
pubmed
25720963
uniprot
proteins
pubmed
27184844
uniprot
proteins
pubmed
27278822
uniprot
proteins
pubmed
28552616
uniprot
proteins
pubmed
29146937
uniprot
proteins
pubmed
30120233
uniprot
proteins
pubmed
31672913
uniprot
proteins
pubmed
32612235
uniprot
proteins
pubmed
32753672
uniprot
proteins
pubmed
33691586
uniprot
proteins
pubmed
34071043
uniprot
proteins
pubmed
35662396
uniprot
proteins
pubmed
36697823
uniprot
proteins
pubmed
36749723
uniprot
proteins
pubmed
37057673
uniprot
proteins
pubmed
37079666
uniprot
proteins
sequence_length
476
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:24081491, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:28552616, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:33691586, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37079666}. Cytoplasm, cytosol {ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:33691586, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37079666}. Lysosome membrane {ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37057673}. Note=Mainly present in the cytoplasm (PubMed:23434374, PubMed:33691586, PubMed:35662396). 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:23401004, PubMed:32612235, PubMed:36697823). Phosphorylation by MTOR prevents nuclear translocation and activity by promoting interaction with 14-3-3 proteins, such as YWHAZ (PubMed:22343943, PubMed:22692423, PubMed:23401004, PubMed:25720963, PubMed:32612235, PubMed:32753672, PubMed:35662396, PubMed:36697823, PubMed:37079666). Under aberrant lysosomal storage conditions, it translocates from the cytoplasm to the nucleus (PubMed:21617040, PubMed:22576015, PubMed:23434374, PubMed:25720963, PubMed:32753672). The translocation to the nucleus is regulated by ATP13A2 (PubMed:23434374, PubMed:27278822). Conversely, inhibition of mTORC1, starvation and lysosomal disruption, promotes dephosphorylation and translocation to the nucleus (PubMed:22343943, PubMed:22692423, PubMed:37079666). Exported from the nucleus in response to nutrient availability (PubMed:30120233). In macrophages, translocates into the nucleus upon live S.enterica infection (PubMed:27184844). {ECO:0000269|PubMed:21617040, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23401004, ECO:0000269|PubMed:23434374, ECO:0000269|PubMed:25720963, ECO:0000269|PubMed:27184844, ECO:0000269|PubMed:27278822, ECO:0000269|PubMed:30120233, ECO:0000269|PubMed:32612235, ECO:0000269|PubMed:32753672, ECO:0000269|PubMed:33691586, ECO:0000269|PubMed:35662396, ECO:0000269|PubMed:36697823, ECO:0000269|PubMed:37079666}.; SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:33691586}. Note=(Microbial infection) Following Coxsackievirus B3 infection, full length TFEB and viral protease 3C-mediated cleavage product are translocated from the cytoplasm to the nucleus. {ECO:0000269|PubMed:33691586}.
uniprot
proteins