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FLASH GENE
Symbol WIF1 contributors: mct - updated : 23-01-2017
HGNC name WNT inhibitory factor 1
HGNC id 18081
DNA
TYPE functioning gene
STRUCTURE 70.94 kb     10 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
cytosine-phosphate-guanine/HTF
text structure
  • promoter may be regulated by the Wnt/beta-catenin pathway and may function in a negative feedback manner
  • methylated CpG island
  • ZBTB17 is a direct activator of WIF1 transcriptional activity, which is found at WIF1 promoter (
    • MAPPING cloned   linked   status
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 2240 - 379 - 2004 15351726
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtoothenamel highly Homo sapiens
    Endocrineneuroendocrinepituitary  highly
    Skin/Tegumentskin     Homo sapiens
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone    Homo sapiens
    Connectivecartilage    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveameloblast Homo sapiens
    Skin/Tegumentmelanocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text highly expressed at cartilage-mesenchyme interfaces of the early developing skeleton
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five 5 EGF-like domains
  • a WIF domain, that is sufficient for Wnt binding and signaling inhibition , and WIF domain is also bound by Wnts at two sites
  • short C-terminal hydrophilic domain
    • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION extracellular
    text
  • localizes to the enamel knot in which WIF1 regulates apoptosis by mediating and regulating WNT-CTNNB1 signaling
    • basic FUNCTION
  • may be involved in mesoderm segmentation
  • antagonist of the Wnt signaling pathway, which plays a critical role in the cancer
  • role of the WIF domain as a palmitoyl binding domain required for WIF1 binding to palmitoylated Wnt and signaling inhibition
  • able to block WNT3a-mediated activation of the canonical Wnt signalling pathway
  • novel extracellular Wnt modulator in cartilage biology
  • downregulated by promoter methylation and functions as a tumor suppressor gene by inducing apoptosis in renal cell carcinoma cells
  • negative regulator of the Wnt-signaling pathway that may have important implications for tumorigenesis
  • vertebrate WIF1 blocks WNT signaling
  • is regulated by androgens and enhances androgen-dependent prostate development
  • melanocytes express WIF1 constitutively and WIF1 promotes melanogenesis in normal human melanocytes
  • WIF1 secretion by the Müllerian ducts (MDs) mesenchyme plays likely a role in MD regression in fetal males
  • regulates cancer stemness and senescence, which might have major implications in the field of cancer biology
  • plays an essential role in tooth development
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component potential novel regulatory loop of BMP4-SMAD1-WIF1-Wnt/beta-catenin in coordinating BMP and Wnt pathways to control fetal lung development
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binds to WNT proteins and inhibits their activities
  • antagonist of WNT signaling and functions by directly binding to WNT ligands in the extracellular space
  • interacting with ADIPOQ (ADIPOQ might elicit its antitumor activities at least partially through promoting WIF1 expressions)
  • interacting with MYC (MYC contributes to WIF1 transcriptional repression in a ZBTB17-dependent manner)
  • HOTAIR directly decreased WIF1 expression by promoting its histone H3K27 methylation in the promoter region and then activated the WNT/CTNNB1 signaling pathway
  • ERBB2, MYC, WIF1, RBM38, PTEN, are involved in the HOTAIR regulation network
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    with HMGA2 in the salivary gland pleomorphic adenoma
    tumoral     --low  
    in salivary gland pleomorphic adenoma in progression
    tumoral     --low  
    in mesothelioma 72-fold compared to normal tissue, and WIF1 promoter methylation is a common event in mesothelioma
    tumoral     --low  
    in 76p100 of examined osteosarcoma cases, with promoter methylation (
    tumoral     --low  
    is frequently downregulated or silenced by promoter methylation in the carcinogenesis of Oral submucous fibrosis (OSF)
    tumoral     --low  
    downregulated by promoter methylation and is an important mechanism of aberrant WNT/CTNNB1 pathway activation in astrocytoma pathogenesis
    tumoral     --low  
    by epigenetic gene silencing is an important mechanism of WNT activation in cervical oncogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbone 
    reexpression of WIF-1 in WIF-1-deficient osteosarcoma represents a potential novel treatment and preventive strategy
    cancerreproductiveuterus
    potent drug target in cervical cancer treatment
    cancerdigestiveoesophagus
    HOTAIR/WIF1 axis represented a novel therapeutic target in patients with esophageal squamous cell carcinoma (ESCC)
    ANIMAL & CELL MODELS