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FLASH GENE
Symbol TFEB contributors: mct - updated : 11-04-2022
HGNC name transcription factor EB
HGNC id 11753
Location 6p21.1      Physical location : 41.651.715 - 41.703.997
Synonym name
  • T-cell transcription factor EB
  • class E basic helix-loop-helix protein 35
  • Synonym symbol(s) ALPHATFEB, BHLHE35, TCFEB, EVI133
    DNA
    TYPE functioning gene
    STRUCTURE 51.08 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map pter - D6S1549 - D6S1672 - TFEB - D6S1552 - D6S400 - qter
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 splicing 2198 - 476 - 2003 12719541
    10 splicing 2364 - 476 - 2003 12719541
    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,nucleus
    text
  • colocalizes with master growth regulator MTOR on the lysosomal membrane
  • MTOR regulates nuclear localization and activity of TFEB
  • 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
  • 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
  • cell & other
    REGULATION
    Phosphorylated by signal-regulated kinase 2 (
    phosphorylated in Ser211 in an MTOR-dependent manner
    ASSOCIATED DISORDERS
    corresponding disease(s)
    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
    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