General Information of Target

Target ID LDTP03002
Target Name Transcription factor EB (TFEB)
Gene Name TFEB
Gene ID 7942
Synonyms
BHLHE35; Transcription factor EB; Class E basic helix-loop-helix protein 35; bHLHe35
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASRIGLRMQLMREQAQQEEQRERMQQQAVMHYMQQQQQQQQQQLGGPPTPAINTPVHFQ
SPPPVPGEVLKVQSYLENPTSYHLQQSQHQKVREYLSETYGNKFAAHISPAQGSPKPPPA
ASPGVRAGHVLSSSAGNSAPNSPMAMLHIGSNPERELDDVIDNIMRLDDVLGYINPEMQM
PNTLPLSSSHLNVYSSDPQVTASLVGVTSSSCPADLTQKRELTDAESRALAKERQKKDNH
NLIERRRRFNINDRIKELGMLIPKANDLDVRWNKGTILKASVDYIRRMQKDLQKSRELEN
HSRRLEMTNKQLWLRIQELEMQARVHGLPTTSPSGMNMAELAQQVVKQELPSEEGPGEAL
MLGAEVPDPEPLPALPPQAPLPLPTQPPSPFHHLDFSHSLSFGGREDEGPPGYPEPLAPG
HGSPFPSLSKKDLDLMLLDDSLLPLASDPLLSTMSPEASKASSRRSSFSMEEGDVL
Target Bioclass
Transcription factor
Family
MiT/TFE family
Subcellular location
Nucleus
Function
Transcription factor that acts as a master regulator of lysosomal biogenesis, autophagy, lysosomal exocytosis, lipid catabolism, energy metabolism and immune response. 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. 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. Upon starvation or lysosomal stress, inhibition of MTOR induces TFEB dephosphorylation, resulting in nuclear localization and transcription factor activity. 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. Regulates lysosomal positioning in response to nutrient deprivation by promoting the expression of PIP4P1. Acts as a positive regulator of autophagy by promoting expression of genes involved in autophagy. 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. Specifically recognizes the gamma-E3 box, a subset of E-boxes, present in the heavy-chain immunoglobulin enhancer. Plays a role in the signal transduction processes required for normal vascularization of the placenta. 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. Itaconate-mediated alkylation activates TFEB-dependent lysosomal biogenesis, facilitating the bacteria clearance during the antibacterial innate immune response. In association with ACSS2, promotes the expression of genes involved in lysosome biogenesis and both autophagy upon glucose deprivation.
Uniprot ID
P19484
Ensemble ID
ENST00000230323.8
HGNC ID
HGNC:11753

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
CHL1 SNV: p.G206S .
JURKAT SNV: p.P377S .
KATOIII SNV: p.I251V .
LS123 SNV: p.N152H .
NCIH446 SNV: p.G357R .
NUGC3 Deletion: p.A364LfsTer37 .
RL952 SNV: p.R465W .
SKNSH SNV: p.G404C .
TOV21G SNV: p.M470I .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
N.A.  LDD2231  [1]

References

1 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377