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FLASH GENE
Symbol HSF4 contributors: mct - updated : 17-04-2010
HGNC name heat shock transcription factor 4
HGNC id 5227
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • lacking the C terminal hydrophobic repeat shared among all vertebrate Heat shock protein
  • DNA binding domain
    • mono polymer homomer , trimer
    HOMOLOGY
    interspecies homolog to murine Hsf4
    Homologene
    FAMILY
  • heat shock transcription factor (HSF) family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    text translocated into nucleus after heat shock
    basic FUNCTION
  • potential repressor of genes for HS proteins and molecular chaperones
  • HSF4b acting as an activator of tissue specific heat shock gene expression
  • HSF4a acting as an inhibitor of tissue specific heat shock gene expression chaperones
  • involved in the negative regulation of DNA binding activity
  • required for the lens development
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • pathway (NBN-HSF4-HSPA4/HSPA14 axis) to induce migration, invasion, and transformation, suggesting the activation of multiple signaling events induced by NBN overexpression
    • a component
  • forming homotrimer even in the absence of stress
    • INTERACTION
    DNA
  • binding specifially to heat shock promoter elements (hse)
  • binding (constitutive)
    • RNA
    small molecule
    protein
  • essential role for HSF4-mediated SKAP2 expression in the regulation of actin reorganization during lens differentiation, likely through a mechanism that SKAP2 anchors the complex of NCK2/focal adhesion to FGF receptors at the lamellipodium in lens epithelial cells
  • HSF2 and HSF4 regulate transcription of HIF1A and a critical balance between these HSF is required to maintain HIF1A expression in a repressed state
  • HSF4 inhibits HSF2 expression or transcriptional activity through negative regulation of HSF2 binding to the HSP70 promoter
  • HSF4 occupies only CRYAB and not HSP70 promoter in epithelial cells, while HSF1 occupies only HSP70 promoter in both cell types, and CRYAB promoter, only in heat shocked fibroblasts
    • cell & other
    REGULATION
    induced by NBN (NBN overexpression induced the expression of HSF4, which correlated with the expression of HSPA4 and HSPA14)
    ASSOCIATED DISORDERS
    corresponding disease(s) CTM
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    leads to defect in lens epithelial cell (LEC) differentiation and cataract formation
    Susceptibility to age related cataract
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorial  
    HSF4-vimentin axis appears to be a new target for developing anti-cataract drugs, especially for those cataracts resulting from aberrations in HSF4 expression
    ANIMAL & CELL MODELS
    sf4 knockout mouse (Hsf4-/-) partially mimics the human cataract caused by HSF4 mutations