InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: WWOX

Summary

InnateDB Protein

IDBP-43135.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

WWOX

Protein Name

WW domain containing oxidoreductase

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000348119

InnateDB Gene

IDBG-43129 (WWOX)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:11719429, ECO:0000269PubMed:15070730, ECO:0000269PubMed:15548692, ECO:0000269PubMed:16061658, ECO:0000269PubMed:16219768, ECO:0000269PubMed:19366691, ECO:0000269PubMed:19465938}.

Subcellular Localization

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. {ECO:0000250}.

Disease Associations

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.Esophageal 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.Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12) [MIM:614322]: Spinocerebellar ataxia is 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 mental retardation. Some patients may also show spasticity. {ECO:0000269PubMed:24369382, ECO:0000269PubMed:24456803}. Note=The disease is caused by mutations affecting the gene represented in this entry.

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. {ECO:0000269PubMed:10786676, ECO:0000269PubMed:11719429}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 260 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	260 [view]
Protein-Protein	260 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0016491	oxidoreductase activity
GO:0019899	enzyme binding
GO:0046983	protein dimerization activity
GO:0048037	cofactor binding
GO:0050662	coenzyme binding

Biological Process

GO:0008152	metabolic 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:2001238	positive regulation of extrinsic apoptotic signaling pathway