ID:WWOX_HUMAN DESCRIPTION: RecName: Full=WW domain-containing oxidoreductase; EC=1.1.1.-; AltName: Full=Fragile site FRA16D oxidoreductase; FUNCTION: Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm. SUBUNIT: Interacts with TP53, p73/TP73 and MAPK8. Interacts with MAPT/TAU, RUNX2 and HYAL2 (By similarity). Forms a ternary complex with TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3. May interact with COTE1/C1orf2 and SCOTIN. Interacts with TNK2. Interacts with TMEM207. INTERACTION: Q61527:Erbb4 (xeno); NbExp=3; IntAct=EBI-4320739, EBI-4398741; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Mitochondrion. Golgi apparatus. Note=Partially localizes to the mitochondria. Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity). Translocates to the nucleus in response to TGFB1. Isoform 5 and isoform 6 may localize in the nucleus. TISSUE SPECIFICITY: Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines. DOMAIN: The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1. PTM: Phosphorylated upon genotoxic stress. Phosphorylation of Tyr- 33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation. PTM: Ubiquitinated when phosphorylated by TNK2, leading to its degradation. DISEASE: Note=Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers. Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect. DISEASE: Defects in WWOX may be a cause of esophageal cancer (ESCR) [MIM:133239]. SIMILARITY: Belongs to the short-chain dehydrogenases/reductases (SDR) family. SIMILARITY: Contains 2 WW domains. SEQUENCE CAUTION: Sequence=AAP94227.1; Type=Frameshift; Positions=362; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/WWOXID508ch16q23.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NZC7
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001649 osteoblast differentiation GO:0006366 transcription from RNA polymerase II promoter GO:0006915 apoptotic process GO:0008202 steroid metabolic process GO:0016055 Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048705 skeletal system morphogenesis GO:0055114 oxidation-reduction process GO:0071560 cellular response to transforming growth factor beta stimulus GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator GO:0097191 extrinsic apoptotic signaling pathway GO:2001238 positive regulation of extrinsic apoptotic signaling pathway GO:2001241 positive regulation of extrinsic apoptotic signaling pathway in absence of ligand
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
