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FLASH GENE
Symbol HSF4 contributors: mct - updated : 17-04-2010
HGNC name heat shock transcription factor 4
HGNC id 5227
Corresponding disease
CTM cataract, congenital, Marner type
Location 16q22.1      Physical location : 67.197.287 - 67.203.848
DNA
TYPE functioning gene
STRUCTURE 6.56 kb     15 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
DNCLI2 16q22.1 dynein, cytoplasmic, light intermediate polypeptide 2 FLJ35894 16q22.1 hypothetical protein FLJ35894 APPBP1 16q22 amyloid beta precursor protein binding protein 1, 59kDa CA7 16q22.1 carbonic anhydrase VII KIAA1348 CDH16 16q22.1 cadherin 16, KSP-cadherin RRAD 16q22 Ras-related associated with diabetes CGI-128 16q22.1-q22.3 CGI-128 protein CES2 16q22.1 carboxylesterase 2 (intestine, liver) FLJ21736 16q22.1 esterase 31 FLJ37464 16q22.1 hypothetical protein FLJ37464 CBFB 16q22.1 core-binding factor, beta subunit Lin10 16q22.1 lin-10 protein homolog MGC4655 16q22.1 hypothetical protein MGC4655 TRADD 16q22 TNFRSF1A-associated via death domain FBXL8 16q23.1 F-box and leucine-rich repeat protein 8 HSF4 16q21 heat shock transcription factor 4 NOL3 16qp21-q23 nucleolar protein 3 (apoptosis repressor with CARD domain) LOC283849 16q22.1 hypothetical protein LOC283849 E2F4 16q22.1 E2F transcription factor 4, p107/p130-binding ELMO3 16q23.1 engulfment and cell motility 3 (ced-12 homolog, C. elegans) FBXL9 16q23-q31 F-box and leucine-rich repeat protein 9 HSPC171 16q22.1 HSPC171 protein FHOD1 16q22 formin homology 2 domain containing 1 SLC9A5 16q22.1 solute carrier family 9 (sodium/hydrogen exchanger), isoform 5 DKFZP434I216 16q22.1 DKFZP434I216 protein FLJ40162 16q22.1 FLJ40162 protein FLJ11004 16q22.1 hypothetical protein FLJ11004 CGI-38 16q22.1 brain specific protein ZDHHC1 16q23.1 zinc finger, DHHC domain containing 1 HSD11B2 16q22 hydroxysteroid (11-beta) dehydrogenase 2 ATP6V0D1 16q22 ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d isoform 1 AGRP 16q22.1 agouti related protein homolog (mouse)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
15 splicing 2532 - 462 heart, brain, pancreas, skeletal muscle 2006 16581800
  • also called HSF4a
  • acting as an inhibitor of tissue specific heat shock gene expression chaperones
  • 15 splicing 2622 52.9 492 pancreas, brain 2010 20219016
  • also called HSF4b
  • acting as an activator of tissue specific heat shock gene expression
  • direct target of the mitogen-activated protein (MAP) kinase extracellular signal-related kinase (ERK) and phosphorylation by ERK leads to increased ability to bind DNA
  • target of SKAP2
  • recruits BRG1 complexes to the promoters of heat shock proteins (HSPs) under physiological growth conditions
  • EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart    
    Digestiveintestinelarge intestinecolon  
    Endocrinepancreas    
     parathyroid    
     thyroid    
    Nervousbrain    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    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