WWOX

This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WW domain containing oxidoreductase

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.

Biological Process cellular response to transforming growth factor beta stimulus Source:BHF-UCL1 Publication
Biological Process extrinsic apoptotic signaling pathway Source:Ensembl
Biological Process intrinsic apoptotic signaling pathway by p53 class mediator Source:Ensembl
Biological Process negative regulation of Wnt signaling pathway Source:UniProtKB1 Publication
Biological Process osteoblast differentiation Source:Ensembl
Biological Process positive regulation of extrinsic apoptotic signaling pathway Source:BHF-UCL
Biological Process positive regulation of extrinsic apoptotic signaling pathway in absence of ligand Source:Ensembl
Biological Process positive regulation of transcription by RNA polymerase II Source:BHF-UCL
Biological Process skeletal system morphogenesis Source:BHF-UCL
Biological Process Wnt signaling pathway Source:UniProtKB-KW

Cytoplasm
Nucleus
Mitochondrion
Golgi apparatus
Partially localizes to the mitochondria (PubMed:14695174).
Translocates to the nucleus upon genotoxic stress or TNF stimulation (By similarity).
Translocates to the nucleus in response to TGFB1 (PubMed:19366691).
Isoform 5 and isoform 6 may localize in the nucleus.

Esophageal cancer (ESCR):
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.
Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12):
A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with intellectual disability. Some patients may also show spasticity.
Developmental and epileptic encephalopathy 28 (DEE28):
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.

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.
Ubiquitinated when phosphorylated by TNK2, leading to its degradation.