NP_057457.1
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NCBI GenBank Nucleotide #
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UniProt Primary Accession #
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UniProt Secondary Accession #
UniProt Related Accession #
NCBI Official Full Name
WW domain-containing oxidoreductase isoform 1
NCBI Official Synonym Full Names
WW domain containing oxidoreductase
NCBI Official Synonym Symbols
FOR; WOX1; FRA16D; HHCMA56; PRO0128; SDR41C1; D16S432E [Similar Products]
NCBI Protein Information
WW domain-containing oxidoreductase; WW domain-containing protein WWOX; fragile site FRA16D oxidoreductase; short chain dehydrogenase/reductase family 41C, member 1
UniProt Protein Name
WW domain-containing oxidoreductase
UniProt Synonym Protein Names
Fragile site FRA16D oxidoreductase
UniProt Synonym Gene Names
UniProt Entry Name
WWOX_HUMAN
NCBI Summary for WWOX
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. [provided by RefSeq, Jul 2008]
UniProt Comments for WWOX
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. Ref.3 Ref.12 Ref.16 Ref.17 Ref.19 Ref.21 Ref.22
Subunit structure: 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 FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207. Ref.10 Ref.12 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.22 Ref.24
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. Ref.9 Ref.15 Ref.16 Ref.19 Ref.21 Ref.22
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. Ref.1 Ref.3
Domain: The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1. Ref.12 Ref.15 Ref.16
Post-translational modification: 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. Ref.16 Ref.18 Ref.19 Ref.21Ubiquitinated when phosphorylated by TNK2, leading to its degradation. Ref.16 Ref.18 Ref.19 Ref.21
Involvement in disease: 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. Ref.4 Ref.11 Ref.13 Ref.14 Ref.20Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.Note: The disease may be caused by mutations affecting the gene represented in this entry. Ref.4 Ref.11 Ref.13 Ref.14 Ref.20
Sequence similarities: Belongs to the short-chain dehydrogenases/reductases (SDR) family.Contains 2 WW domains.
Sequence caution: The sequence AAP94227.1 differs from that shown. Reason: Frameshift at position 362.
Research Articles on WWOX
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Pathways associated with WWOX peptide
Diseases associated with WWOX peptide
Organs/Tissues associated with WWOX peptide
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