Search
WW domain-containing oxidoreductase; fragile site FRA16D oxidoreductase (WWOX, FOR, WOX1)
Function:
- putative oxidoreductase
- tumor suppressor
- role in apoptosis
- required for normal bone development (putative)
- may function synergistically with TP53/p53 to control genotoxic stress-induced cell death
- role in TGFB1 signaling & TGFB1-mediated cell death
- role in TNF-mediated cell death (putative)
- inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm
- phosphorylated upon genotoxic stress
- phosphorylation of Tyr-33 regulates interaction with TP53,TP73 & MAPK8
- phosphorylation may also regulate proapoptotic activity
- phosphorylation by TNK2 is associated with polyubiquitination & degradation
- interacts with TP53, TP73/p73 & MAPK8.
- interacts with MAPT/TAU, RUNX2 & HYAL2 (putative)
- forms a ternary complex with TP53 & MDM2
- interacts with ERBB4, LITAF & WBP1
- interacts with DVL1, DVL2 & DVL3
- interacts with TNK2
- interacts with TMEM207
- may interact with COTE1/C1orf2 (FAM189B) & SCOTIN
Structure:
- belongs to the short-chain dehydrogenases/reductases (SDR) family
- contains 2 WW domains WW 1 domain mediates interaction with TP53, & probably TP73, TFAP2C, LITAF & WBP1
Compartment:
- cytoplasm, nucleus, mitochondrion, Golgi
- partially localizes to the mitochondria
- translocates to nucleus upon genotoxic stress or TNF stimulation
- isoforms 5 & 6 may localize in the nucleus
Alternative splicing: named isoforms=7
Expression:
- widely expressed
- strongly expressed in testis, prostate, ovary
Pathology:
- overexpressed in cancer cell lines
- isoforms 5 & 6 may only be expressed in tumor cell lines
- defects in WWOX may be involved in several cancer types
- alteration of WWOX expression & expression of some WWOX isoforms is associated with cancers; however, it is unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect
- defects in WWOX may be involved in esophageal cancer (esophageal squamous cell carcinoma)
- defects in WWOX may be the cause of
- spinocerebellar ataxia, autosomal recessive 12 (SACR12)
- early infantile epileptic encephalopathy 28 (EIEE28)
Genetics:
- WWOX gene spans the 2nd most common chromosomal fragile site (FRA16D) which is frequently altered in cancers
Related
WW domain-containing oxidoreductase (WWOX) gene
General
human longevity protein
oxidoreductase
phosphoprotein
Properties
SIZE: MW = 47 kD
entity length = 414 aa
COMPARTMENT: mitochondria
cytoplasm
cell nucleus
golgi
MOTIF: Ser phosphorylation site {S14}
WW domain (W/rsp5/WWP domain) {16-49}
MOTIF: Tyr phosphorylation site {Y33}
nuclear translocation signal {50-55}
WW domain (W/rsp5/WWP domain) {57-90}
MAPT interaction {125-414}
MOTIF: cofactor-binding site [131-137]
COFACTOR-BOUND: NAD
mitochondrial targetting {209-273}
binding site
SITE: 260-260
FOR-BINDING-OF: Substrate
tyrosine residue {Y293}
Database Correlations
OMIM correlations
MORBIDMAP 605131
UniProt Q9NZC7
PFAM correlations
Entrez Gene 51741
Kegg hsa:51741
References
- UniProt :accession Q9NZC7
- UniProt PubMed refs
- PMID: 15070730
- PMID: 070730
- PMID: 16061658
- PMID: 061658
- PMID: 19366691
- PMID: 366691
- PMID: 514174
- PMID: 16288044
- PMID: 288044
- PMID: 19465938
- PMID: 465938
- PMID: 15548692
- PMID: 16219768
- PMID: 219768
- PMID: 14695174
- PMID: 695174
- PMID: 10861292
- PMID: 15073125
- PMID: 11572989
- PMID: 572989
- PMID: 15131042
- PMID: 131042
- PMID: 24456803
- Atlas of Genetics & Cytogenetics in Oncology & Haematology
http://atlasgeneticsoncology.org/genes/WWOXID508ch16q23.html