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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
DNA
TYPE functioning gene
STRUCTURE 1113.01 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
text structure extending over a region of 1mb
MAPPING cloned Y linked N status confirmed
Map cen - D16S518 - WWOX - D16S3029 - D16S3096 - D16S504 - qter
Text see TSG16A
regionally located in the D16S516 deleted region
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
6 splicing 735 - 189 tumoral tissu 2009 19465938
  • also called FORI-Variant 2
  • a partial deletion of exon 9 with a unique C-terminus
  • 9 splicing 2264 46 414 normal or tumoral tissu 2009 19465938
    also called FORII
    1 splicing 545 - 36 tumoral tissu 2009 19465938
  • also called FORIII-Variant 3
  • lack exons 6,7,8
  • an out-of-frame deletion of exon 5-8 and frame-shift at the C-terminus
  • EXPRESSION
    Type widely
    constitutive of
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticspleen   highly
    Endocrinethyroid   highly
    Lymphoid/Immunethymus    
    Nervousbrain    
     nerve    
    Reproductivefemale systembreastmammary gland highly
     female systemovary  highly
     male systemtestis  highly
     male systemprostate  highly
    Respiratorylung    
    Urinarykidney    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines breast cancer cell lines
    fluid/secretion
    at STAGE
    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