From Wikipedia, the free encyclopedia
Jump to: navigation, search
WW domain containing oxidoreductase
Protein WWOX PDB 1wmv.png
PDB rendering based on 1wmv.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols WWOX ; D16S432E; FOR; FRA16D; HHCMA56; PRO0128; SCAR12; SDR41C1; WOX1
External IDs OMIM605131 MGI1931237 HomoloGene56334 GeneCards: WWOX Gene
EC number 1.1.1.-
RNA expression pattern
PBB GE WWOX 221147 x at tn.png
More reference expression data
Species Human Mouse
Entrez 51741 80707
Ensembl ENSG00000186153 ENSMUSG00000004637
UniProt Q9NZC7 Q91WL8
RefSeq (mRNA) NM_001291997 NM_019573
RefSeq (protein) NP_001278926 NP_062519
Location (UCSC) Chr 16:
78.13 – 79.25 Mb
Chr 8:
114.44 – 115.35 Mb
PubMed search [1] [2]

WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.[1][2][3][4]


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.[4]

WWOX is also known as human accelerated region 6. It may, therefore, have played a key role in differentiating humans from apes.[5]


WWOX has been shown to interact with P53 and ACK1.[6][7]


  1. ^ 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. 
  2. ^ Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK et al. (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. 
  3. ^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD et al. (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. 
  4. ^ a b "Entrez Gene: WWOX WW domain containing oxidoreductase". 
  5. ^ Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS et al. (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
  6. ^ Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB et al. (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. 
  7. ^ 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. doi:10.1158/0008-5472.can-05-1127. PMID 16288044. 

Further reading[edit]