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Protein WWOX PDB 1wmv.png
Available structures
PDBOrtholog search: PDBe RCSB
AliasesWWOX, D16S432E, FOR, FRA16D, HHCMA56, PRO0128, SCAR12, SDR41C1, WOX1, EIEE28, WW domain containing oxidoreductase
External IDsMGI: 1931237 HomoloGene: 56334 GeneCards: WWOX
Gene location (Human)
Chromosome 16 (human)
Chr.Chromosome 16 (human)[1]
Chromosome 16 (human)
Genomic location for WWOX
Genomic location for WWOX
Band16q23.1-q23.2Start78,099,413 bp[1]
End79,212,667 bp[1]
RNA expression pattern
PBB GE WWOX 221147 x at fs.png
More reference expression data
RefSeq (mRNA)


RefSeq (protein)



Location (UCSC)Chr 16: 78.1 – 79.21 MbChr 8: 114.44 – 115.35 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.[5][6][7][8]


WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 2 WW domains and a short-chain dehydrogenase/reductase domain (SRD). The highest normal expression of this gene is detected in hormonally regulated tissues such as testis, ovary, and prostate. This expression pattern and the presence of an SRD domain suggest a role for this gene in steroid metabolism. The encoded protein is more than 90% identical to the mouse protein, which is an essential mediator of tumor necrosis factor-alpha-induced apoptosis, suggesting a similar, important role in apoptosis for the human protein. In addition, there is evidence that this gene behaves as a suppressor of tumor growth. Alternative splicing of this gene generates transcript variants that encode different isoforms.[8]

WWOX is also known as human accelerated region 6. It may, therefore, have played a key role in differentiating humans from apes.[9]


WWOX has been shown to interact with P53 and ACK1.[10][11]


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000186153 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004637 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:".
  4. ^ "Mouse PubMed Reference:".
  5. ^ Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM (May 2000). "WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer". Cancer Res. 60 (8): 2140–5. PMID 10786676.
  6. ^ Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, Woollatt E, Kremmidiotis G, Gardner A, Venter D, Baker E, Richards RI (Sep 2000). "Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells". Hum Mol Genet. 9 (11): 1651–63. doi:10.1093/hmg/9.11.1651. PMID 10861292.
  7. ^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, Duarte RG, Jörnvall H, Kavanagh KL, Kedishvili N, Kisiela M, Maser E, Mindnich R, Orchard S, Penning TM, Thornton JM, Adamski J, Oppermann U (Feb 2009). "The SDR (Short-Chain Dehydrogenase/Reductase and Related Enzymes) Nomenclature Initiative". Chem Biol Interact. 178 (1–3): 94–8. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
  8. ^ a b "Entrez Gene: WWOX WW domain containing oxidoreductase".
  9. ^ Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M, Vanderhaeghen P, Haussler D (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature. 443 (7108): 167–72. doi:10.1038/nature05113. PMID 16915236. supplement
  10. ^ Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N (February 2001). "Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity". J. Biol. Chem. 276 (5): 3361–70. doi:10.1074/jbc.M007140200. PMID 11058590.
  11. ^ Mahajan NP, Whang YE, Mohler JL, Earp HS (November 2005). "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox". Cancer Res. 65 (22): 10514–23. CiteSeerX doi:10.1158/0008-5472.can-05-1127. PMID 16288044.

Further reading[edit]