{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q9NZC7","secondaryAccessions":["A8K323","Q5MYT5","Q96KM3","Q96RF2","Q9BTT8","Q9NPC9","Q9NRF4","Q9NRF5","Q9NRF6","Q9NRK1","Q9NZC5"],"uniProtkbId":"WWOX_HUMAN","entryAudit":{"firstPublicDate":"2005-11-22","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2000-10-01","entryVersion":213,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"WW domain-containing oxidoreductase"},"ecNumbers":[{"value":"1.1.1.-"}]},"alternativeNames":[{"fullName":{"value":"Fragile site FRA16D oxidoreductase"}},{"fullName":{"value":"Short chain dehydrogenase/reductase family 41C member 1"}}]},"genes":[{"geneName":{"value":"WWOX"},"synonyms":[{"value":"FOR"},{"value":"SDR41C1"},{"value":"WOX1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11719429"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15070730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15548692"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16061658"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16219768"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19366691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19465938"}],"value":"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"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12514174"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15064722"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15070730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15548692"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16061658"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16219768"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16288044"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19366691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19465938"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22226915"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30285739"}],"value":"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. Interacts (via WW domain) with VOPP1 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Localized to the lysosome probably upon binding to VOPP1 (PubMed:30285739)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14695174"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15070730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16219768"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19366691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19465938"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14695174"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15064722"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16219768"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19366691"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14695174"}],"value":"Mitochondrion","id":"SL-0173"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30285739"}],"value":"Golgi apparatus","id":"SL-0132"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30285739"}],"value":"Lysosome","id":"SL-0158"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"synonyms":[{"value":"FOR II"},{"value":"FOR2"},{"value":"WWOXv1"},{"value":"WWOX v8"}],"isoformIds":["Q9NZC7-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"synonyms":[{"value":"FOR I"},{"value":"FOR1"},{"value":"WOX2"},{"value":"WWOXv2"}],"isoformIds":["Q9NZC7-2"],"sequenceIds":["VSP_016367","VSP_016369"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"synonyms":[{"value":"FOR III"},{"value":"FOR3"},{"value":"WOX3"}],"isoformIds":["Q9NZC7-3"],"sequenceIds":["VSP_016364","VSP_016365"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"synonyms":[{"value":"FOR IV"}],"isoformIds":["Q9NZC7-4"],"sequenceIds":["VSP_016358","VSP_016359"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"synonyms":[{"value":"WWOXdelta6-8"},{"value":"WWOXv4"}],"isoformIds":["Q9NZC7-5"],"sequenceIds":["VSP_016363"],"isoformSequenceStatus":"Described"},{"name":{"value":"6"},"synonyms":[{"value":"WWOXdelta5-8"},{"value":"WWOXv3"}],"isoformIds":["Q9NZC7-6"],"sequenceIds":["VSP_016360"],"isoformSequenceStatus":"Described"},{"name":{"value":"7"},"isoformIds":["Q9NZC7-7"],"sequenceIds":["VSP_016362","VSP_016366"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10786676"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11719429"}],"value":"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"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15064722"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15070730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15548692"}],"value":"The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15070730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16288044"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19366691"}],"value":"Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate pro-apoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16288044"}],"value":"Ubiquitinated when phosphorylated by TNK2, leading to its degradation"}],"commentType":"PTM"},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10861292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11572989"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15073125"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15131042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15266310"}],"value":"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 (PubMed:10861292). 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 (PubMed:10861292, PubMed:11572989, PubMed:15073125, PubMed:15131042, PubMed:15266310)"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Esophageal cancer","diseaseAccession":"DI-01537","acronym":"ESCR","description":"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.","diseaseCrossReference":{"database":"MIM","id":"133239"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11956080"}]},"note":{"texts":[{"value":"The disease may be caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Spinocerebellar ataxia, autosomal recessive, 12","diseaseAccession":"DI-04025","acronym":"SCAR12","description":"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. 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