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FLASH GENE
Symbol WWOX contributors: mct/npt/pgu - updated : 13-01-2013
HGNC name WW domain containing oxidoreductase
HGNC id 12799
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
two N-terminal WW domains :
  • first WW domain has two conserved tryptophans
  • the second WW domain has only one), with caspase-recognition motif QETD (amino acid 65-68) in the second WW domain
  • a nuclear localization signal (NLS)
  • a central short-chain dehydrogenase/reductase domain
  • a typical C-terminal short-chain alcohol dehydrogenase
    • reductase (SDR) domain
    HOMOLOGY
    interspecies homolog to murine Wox1
    Homologene
    FAMILY
  • short-chain dehydrogenases/reductases (SDR) family
    • CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,organelle,endoplasmic reticulum ,rough,smooth
    intracellular,cytoplasm,organelle,Golgi
    intracellular,nucleus
    basic FUNCTION
  • potentially involved in steroid metabolism
  • playing a role in protein-protein interaction
  • target of FRA16D and potent suppressor of tumor
  • inducing cell growth inhibition and apoptosis in lung cancer cells
  • involved in embryonic development and differentiation, and probably having a homeostatic role in normal cell-cycle progression in concert with TP53, TP73, ERBB4 and other transcription factors
  • playing a protective role where aberrant expression, as a result of breakage at the associated fragile site, could contribute directly to cancer progression
  • required in postnatal survival, growth, and metabolism and may play a central role in regulation of bone tissue formation
  • suppresses prostate cancer cell growth through modulation of ERBB2-mediated androgen receptor signaling
  • playing an important role in fundamental cellular processes, including survival, growth, bone metabolism, and neoplastic transformation
  • tumor suppressor gene involved in apoptosis
  • important proapoptotic protein
  • inhibitor of the Wnt/beta-catenin pathway and would act, at least in part, by preventing the nuclear import of the Dvl proteins
  • suppresses the transactivation function of several transcription factors implied in neoplasia by sequestering them in the cytoplasm
  • participates in a number of cellular processes including growth, differentiation, apoptosis, and tumor suppression
  • involved in numerous important signal pathways for bone and germ-cell development, cellular and animal growth and death, transcriptional control and suppression of cancer development
  • critical role in preventing tumorigenesis in breast cancer
    • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, post translation, targeting
    PHYSIOLOGICAL PROCESS mitochondrial transport
    text putatively involved in regulation of apoptosis
    PATHWAY
    metabolism other
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with TP73 (increasing WWOX proapoptotic activity)
  • interacts with proline-tyrosine rich motif-containing proteins
  • physically associates with RUNX2, the principal transcriptional regulator of osteoblast differentiation, and on osteocalcin chromatin (functionally suppresses RUNX2 transactivation ability in osteoblasts)
  • interacting with ERBB4
  • associates with proline-rich motifs of SIMPLE and EZRIN and with proteins lacking the PPXY motif such as TP53 and c-Jun N-terminal kinase (JNK)
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) EIEE28 , SCAEMR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    in primary acute leukemia often in association with FHIT alterations
    tumoral     --over  
    in breast cancer
    tumoral   LOH    
    in ovarian cancer cells and different cell lines
    tumoral     --low  
    in non-invasive breast and gastric cancer tissues
    tumoral   deletion    
    in adenocarcinomas of colon, stomach, lung, ovary, prostate carcinoma
    tumoral   translocation    
    in multiple myeloma, translocation t(14;16) (q32;q23)
    tumoral     --low  
    in primary oral squamous cell carcinomas, and in prostate carcinoma
    tumoral   LOH    
    in multiple myeloma with poor prognosis
    tumoral     --low  
    is an important step that might increase the vulnerability to the carcinogenesis process in papillary thyroid carcinomas
    constitutional germinal mutation      
    associated with a 46,XY DSD
    Susceptibility
  • to low plasma HDL cholesterol an to coronary artery disease
  • to autism spectrum disorder (ASD)
    • Variant & Polymorphism other
  • variant associated to low plasma HDL cholesterol
  • copy-number variants (CNVs) in WWOX contribute significantly to autism spectrum disorder (ASD) risk
    • Candidate gene
  • target for DNA instability at 16q23.2
  • role in human gonad development
    • Marker
    Therapy target potential target for lung cancer prevention and therapy
    ANIMAL & CELL MODELS
    Wwox KO mouse models showing gonadal abnormalities