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FLASH GENE
Symbol TFEB contributors: mct - updated : 11-04-2022
HGNC name transcription factor EB
HGNC id 11753
EXPRESSION
Type
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Reproductivefemale systemplacenta  highly Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text eye, lens, eye anterior segment, retina foveal, macular, RPE, choroid
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HLH and ZIP domains
HOMOLOGY
interspecies ortholog to Tfeb, Mus musculus
ortholog to Tfeb, Rattus norvegicus
ortholog to tfeb, Danio rerio
ortholog to TFEB, Pan troglodytes
Homologene
FAMILY basic Helix-Loop-Helix-Zipper family of transcription factors
CATEGORY transcription factor , receptor membrane kinase
SUBCELLULAR LOCALIZATION     intracellular
intracellular,cytoplasm,organelle,membrane
intracellular,cytoplasm,organelle,lysosome
intracellular,cytoplasm,cytosolic
intracellular,nucleus
text
  • colocalizes with master growth regulator MTOR on the lysosomal membrane
  • MTOR regulates nuclear localization and activity of TFEB
  • TFEB subcellular localization is dynamically controlled by its continuous shuttling between the cytosol and the nucleus, with the nuclear export representing a limiting step
  • basic FUNCTION
  • plays a critical role in the signal transduction processes required for normal vascularization of the placenta
  • endogenous TFE3 and/or TFEB was required for endogenous CDH1 expression in embryonic kidney cells
  • TFE3 and TFEB are broadly expressed transcription factors related to the transcription factor MITF
  • TFE3 and TFEB are direct, physiological and mutually redundant activators of CD40LG expression in activated CD4(+) T cells critical for T cell-dependent antibody responses
  • a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes
  • required for the expression of a large subset of MTOR responsive genesb
  • regulates lysosomal exocytosis
  • master regulator of lysosomal biogenesis
  • active TFEB also associates with late endosomal/lysosomal membranes through interaction with the LAMTOR/RRAG/MTOR complex
  • TFEB alone was capable of reducing HTT aggregation and neurotoxicity
  • is a master regulator for transcription of genes involved in autophagy and lysosome biogenesis
  • TFEB is a master modulator of autophagy and lysosomal biogenesis
  • promotes expression of endocytic genes and increases rates of cellular endocytosis during homeostatic baseline and starvation conditions
  • functions of TFEB expand its role beyond regulation of the autophagic pathway in the vascular system
  • is a master regulator of tumor-associated macrophages in breast cancer
  • is a master regulator of autophagy and lysosomal biogenesis
  • TFEB is required for PDCD4-mediated lysosomal function suppression
  • TFEB-mediated control of lysosomal activity is a central regulatory hub for proper and coordinated stem cell fate determination
  • TFEB downregulation plays a vital role in the development of pressure overload-induced cardiac hypertrophy
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
  • E-box sequences in the heavy-chain immunoglobulin enhancer (
  • RNA
    small molecule
    protein
  • MITF, TFE3 and TFEC (
  • TFE3 and TFEB are cell type-specific leukemia inhibitory factor-responsive activators of E-cadherin (CDH1)
  • tends to bind to the core promoters of its targets genes
  • TFEB targets control multiple sequential steps of at least five degradation pathways, including the degradation of heparan and keratan sulfate *
  • also targets genes encoding the subunits of the vacuolar proton pump, which creates and maintains the lysosomal acidic environment
  • interacting with MTOR (coordinately regulates TFEB phosphorylation and nuclear localization and in a manner dependent on both TFEB and ATP6VH, MTOR promotes endocytosis)
  • interacting with the Rag GTPase complex, which senses lysosomal amino acids and activates MTOR, and is both necessary and sufficient to regulate starvation- and stress-induced nuclear translocation of TFEB
  • PPARGC1A promoted HTT turnover and the elimination of protein aggregates by activating TFEB, a master regulator of the autophagy-lysosome pathway
  • interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to MTOR-dependent phosphorylation and inhibition of TFEB
  • lysosomal Ca2+ release through MCOLN1 activates PPP3CA, which binds and dephosphorylates &
  • 8203;TFEB, thus promoting its nuclear translocation
  • KDM7A mediates TNF-induced ICAM1 protein upregulation mediated by induction of KDM7A, which regulates the TFEB-mediated lysosomal activity
  • STUB1, a chaperone-dependent E3 ubiquitin ligase, modulates TFEB activity by preferentially targeting inactive phosphorylated TFEB for degradation by the ubiquitin-proteasome pathway
  • TFEB nucleo-cytoplasmic shuttling suggest an unpredicted role of MTOR in nuclear export
  • TFEB-mediated endocytosis is a critical process leading to activation of MTOR and autophagic function, thus identifying the importance of the dynamic endolysosomal system in cellular clearance
  • KAT2A is a specific TFEB acetyltransferase, and acetylation by KAT2A results in the decrease in TFEB transcriptional activity
  • PDCD4, a tumor suppressor, decreased levels of nuclear TFEB to inhibit lysosome biogenesis and function
  • MTOR specifically controls TFEB and TFE3 cytosolic retention, whereas AMPK is essential for TFEB and TFE3 transcriptional activity
  • novel function of GABARAPL1 to activate TFEB, a master transcription factor of autophagy and lysosome function during lysosomal damage
  • cell & other
    REGULATION
    Phosphorylated by signal-regulated kinase 2 (
    phosphorylated in Ser211 in an MTOR-dependent manner
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    BYSL-TFEB fusion in sarcomatoid renal cell tumor
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    metabolismlysosome 
    induction of lysosomal exocytosis by TFEB overexpression rescued pathologic storage and restored normal cellular morphology in lysosomal storage diseases (LSDs)
    neurologyneurodegenerativehuntington chorea
    PPARGC1A upstream of TFEB are important therapeutic targets in HD and potentially other neurodegenerative disorders caused by protein misfolding
    cancerreproductivebreast
    pharmacological activation of TFEB would be a promising therapeutic approach to improve the efficacy of existing treatment including immune therapies for breast cancer
    cardiovascularcardiomyopathy 
    Activation of TFEB represents a potential therapeutic strategy for treating cardiac hypertrophy
    ANIMAL & CELL MODELS
  • mice with a targeted disruption of Tfeb die between 9.5 and 10.5 days in embryonic development and have severe defects in placental vascularization
  • combined inactivation of Tfe3 and TfeB in T cells resulted in a hyper-immunoglobulin M syndrome due to impaired expression of CD40 ligand by CD4(+) T cells