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FLASH GENE
Symbol WIF1 contributors: mct - updated : 23-01-2017
HGNC name WNT inhibitory factor 1
HGNC id 18081
Location 12q14.3      Physical location : 65.444.403 - 65.515.346
Synonym symbol(s) WIF-1, UNQ191/PRO217
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
    Physical map
    KIAA1040 12q14.1 KIAA1040 protein FLJ25590 12q14.1 hypothetical protein FLJ25590 ARHCL1 12q14.1 ras homolog gene family, member C like 1 LOC390337 12 similar to RIKEN cDNA A430075L18 gene LOC144581 12q14.1 similar to ribosomal protein L14; 60S ribosomal protein L14 LOC121498 12q14.1 similar to lactate dehydrogenase A -like AVPR1A 12q14 arginine vasopressin receptor 1A FLJ32949 12q14.1 hypothetical protein FLJ32949 LOC390338 12 similar to T-box transcription factor TBX20 TMEM5 12q14.1 transmembrane protein 5 LOC341315 12q14.1 similar to Polyadenylate-binding protein 1 (Poly(A)-binding protein 1) (PABP 1) SRGAP1 12q13.13 SLIT-ROBO Rho GTPase activating protein 1 FLJ32549 12q14.1 hypothetical protein FLJ32549 LOC115749 12q14.1 hypothetical protein LOC115749 LOC390339 12 similar to 40S ribosomal protein S11 XPOT 12q14 exportin, tRNA (nuclear export receptor for tRNAs) TBK1 13q14.2-q14.3 TANK-binding kinase 1 RASSF3 12q14.1 Ras association (RalGDS/AF-6) domain family 3 GNS 12q14 glucosamine (N-acetyl)-6-sulfatase (Sanfilippo disease IIID) KIAA0984 12q13.13 glucosamine (N-acetyl)-6-sulfatase (Sanfilippo disease IIID) WIF1 12q13.13 WNT inhibitory factor 1 MAN1 12q14 WNT inhibitory factor 1 LOC253827 12q14.1 hypothetical protein LOC253827 LOC387865 12 LOC387865 LOC204010 12q14.2 similar to 40S ribosomal protein SA (P40) (34/67 kDa laminin receptor) HMGA2 12q14-q15 high mobility group AT-hook 2 LOC341321 12q14.2 similar to 60S ribosomal protein L21 MGC14817 12q14.2 hypothetical protein MGC14817 CGI-119 12q14.1-q15 CGI-119 protein IRAK3 12q13.13 interleukin-1 receptor-associated kinase 3 RBMS1P 12q14.2 RNA binding motif, single stranded interacting protein 1, pseudogene LOC387866 12 LOC387866 LOC390340 12 similar to IAP-associated factor VIAF1; phosducin-like 2 HELB 12q14.2 helicase (DNA) B GRIP1 12q14.1-q14.2 glutamate receptor interacting protein 1 HGT2 12q14.3 glutamate receptor interacting protein 1 TIP120A 12q14 glutamate receptor interacting protein 1 LOC390341 12 similar to nuclear localization signal containing protein deleted in Velo-Cardio-Facial syndrome DYRK2 12q14.3 dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 2
    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