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WWOX
Identifiers
Aliases	WWOX, D16S432E, FOR, FRA16D, HHCMA56, PRO0128, SCAR12, SDR41C1, WOX1, EIEE28, WW domain containing oxidoreductase, DEE28
External IDs	OMIM: 605131; MGI: 1931237; GeneCards: WWOX
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1WMV
Gene location (Human)
Chr.	Chromosome 16 (human)
End	79,212,667 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	116,079,447 bp
RNA expression pattern
	Top expressed in
	parotid gland; ; optic nerve; ; glomerulus; ; sural nerve; ; metanephric glomerulus; ; Epithelium of choroid plexus; ; pars reticulata; ; endothelial cell; ; kidney tubule; ; pars compacta;
	Top expressed in
	interventricular septum; ; neural layer of retina; ; zygote; ; amygdala; ; visual cortex; ; cerebellar cortex; ; secondary oocyte; ; primary visual cortex; ; spermatocyte; ; lens;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	transcription coactivator activity; protein dimerization activity; protein binding; enzyme binding; oxidoreductase activity;
Cellular component	cytoplasm; cytosol; Golgi apparatus; plasma membrane; microvillus; RNA polymerase II transcription regulator complex; mitochondrion; nucleus;
Biological process	cellular response to transforming growth factor beta stimulus; steroid metabolic process; extrinsic apoptotic signaling pathway; negative regulation of Wnt signaling pathway; skeletal system morphogenesis; Wnt signaling pathway; positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; osteoblast differentiation; intrinsic apoptotic signaling pathway by p53 class mediator; positive regulation of extrinsic apoptotic signaling pathway; positive regulation of transcription by RNA polymerase II; apoptotic process; negative regulation of transcription by RNA polymerase II; transcription by RNA polymerase II;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	51741
	80707
	ENSG00000186153
	ENSMUSG00000004637
	Q9NZC7
	Q91WL8
NM_001291997; NM_016373; NM_018560; NM_130788; NM_130790;
	NM_130791; NM_130792; NM_130844
	NM_019573
	NP_001278926; NP_057457; NP_570607
	NP_062519
	Wikidata
View/Edit Human	View/Edit Mouse

WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.^[5]^[6]^[7]^[8]

Gene

Alternative splicing of this gene generates transcript variants that encode different isoforms.^[8]

Structure

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).

Function

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.

WWOX is also known as human accelerated region 6. It may, therefore, have played a key role in differentiating humans from apes.^[9]

Interactions

WWOX has been shown to interact with P53 and ACK1.^[10]^[11]

Disorders

Defects in the WWOX gene are associated with a number of developmental disorders, including WOREE syndrome.^[12]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000186153 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000004637 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM (May 2000). "WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer". Cancer Research. 60 (8): 2140–2145. PMID 10786676.
^ Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, et al. (September 2000). "Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells". Human Molecular Genetics. 9 (11): 1651–1663. doi:10.1093/hmg/9.11.1651. PMID 10861292.
^ Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (February 2009). "The SDR (Short-Chain Dehydrogenase/Reductase and Related Enzymes) Nomenclature Initiative". Chemico-Biological Interactions. 178 (1–3): 94–98. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.
^ ^a ^b "Entrez Gene: WWOX WW domain containing oxidoreductase".
^ Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, et al. (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature. 443 (7108): 167–172. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. hdl:2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/51805. PMID 16915236. S2CID 18107797. supplement
^ Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, et al. (February 2001). "Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity". The Journal of Biological Chemistry. 276 (5): 3361–3370. doi:10.1074/jbc.M007140200. PMID 11058590.
^ Mahajan NP, Whang YE, Mohler JL, Earp HS (November 2005). "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox". Cancer Research. 65 (22): 10514–10523. doi:10.1158/0008-5472.can-05-1127. PMID 16288044.
^ Piard J, Hawkes L, Milh M, Villard L, Borgatti R, Romaniello R, et al. (June 2019). "The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature". Genetics in Medicine. 21 (6): 1308–1318. doi:10.1038/s41436-018-0339-3. PMC 6752669. PMID 30356099.

Ramos D, Aldaz CM (2006). "WWOX, a Chromosomal Fragile Site Gene and its Role in Cancer". New trends in cancer for the 21st century. Advances in Experimental Medicine and Biology. Vol. 587. pp. 149–159. doi:10.1007/978-1-4020-5133-3_14. ISBN 978-1-4020-4966-8. PMID 17163164.
Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, et al. (2001). "WWOX: A candidate tumor suppressor gene involved in multiple tumor types". Proceedings of the National Academy of Sciences of the United States of America. 98 (20): 11417–11422. Bibcode:2001PNAS...9811417P. doi:10.1073/pnas.191175898. PMC 58744. PMID 11572989.
Bednarek AK, Keck-Waggoner CL, Daniel RL, Laflin KJ, Bergsagel PL, Kiguchi K, et al. (2001). "WWOX, the FRA16D gene, behaves as a suppressor of tumor growth". Cancer Research. 61 (22): 8068–8073. PMID 11719429.
Kuroki T, Trapasso F, Shiraishi T, Alder H, Mimori K, Mori M, et al. (2002). "Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma". Cancer Research. 62 (8): 2258–2260. PMID 11956080.
Chang NS, Doherty J, Ensign A (2003). "JNK1 physically interacts with WW domain-containing oxidoreductase (WOX1) and inhibits WOX1-mediated apoptosis". The Journal of Biological Chemistry. 278 (11): 9195–9202. doi:10.1074/jbc.M208373200. PMID 12514174.
Ludes-Meyers JH, Bednarek AK, Popescu NC, Bedford M, Aldaz CM (2004). "WWOX, the common chromosomal fragile site, FRA16D, cancer gene". Cytogenetic and Genome Research. 100 (1–4): 101–110. doi:10.1159/000072844. PMC 4150470. PMID 14526170.
Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hirakawa K, et al. (2004). "An opposing view on WWOX protein function as a tumor suppressor". Cancer Research. 63 (24): 8629–8633. PMID 14695174.
Chen ST, Chuang JI, Wang JP, Tsai MS, Li H, Chang NS (2004). "Expression of WW domain-containing oxidoreductase WOX1 in the developing murine nervous system". Neuroscience. 124 (4): 831–839. doi:10.1016/j.neuroscience.2003.12.036. PMID 15026124. S2CID 14784743.
Ishii H, Mimori K, Vecchione A, Sutheesophon K, Fujiwara T, Mori M, et al. (2004). "Effect of exogenous E2F-1 on the expression of common chromosome fragile site genes, FHIT and WWOX". Biochemical and Biophysical Research Communications. 316 (4): 1088–1093. doi:10.1016/j.bbrc.2004.02.159. PMID 15044096.
Ludes-Meyers JH, Kil H, Bednarek AK, Drake J, Bedford MT, Aldaz CM (2004). "WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins". Oncogene. 23 (29): 5049–5055. doi:10.1038/sj.onc.1207680. PMC 4143251. PMID 15064722.
Aqeilan RI, Pekarsky Y, Herrero JJ, Palamarchuk A, Letofsky J, Druck T, et al. (2004). "Functional association between Wwox tumor suppressor protein and p73, a p53 homolog". Proceedings of the National Academy of Sciences of the United States of America. 101 (13): 4401–4406. Bibcode:2004PNAS..101.4401A. doi:10.1073/pnas.0400805101. PMC 384759. PMID 15070730.
Kuroki T, Yendamuri S, Trapasso F, Matsuyama A, Aqeilan RI, Alder H, et al. (2004). "The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis". Clinical Cancer Research. 10 (7): 2459–2465. doi:10.1158/1078-0432.CCR-03-0096. PMID 15073125. S2CID 5830887.
Guler G, Uner A, Guler N, Han SY, Iliopoulos D, Hauck WW, et al. (2004). "The fragile genes FHIT and WWOX are inactivated coordinately in invasive breast carcinoma". Cancer. 100 (8): 1605–1614. doi:10.1002/cncr.20137. PMID 15073846. S2CID 23157412.
Sze CI, Su M, Pugazhenthi S, Jambal P, Hsu LJ, Heath J, et al. (2004). "Down-regulation of WW domain-containing oxidoreductase induces Tau phosphorylation in vitro. A potential role in Alzheimer's disease". The Journal of Biological Chemistry. 279 (29): 30498–30506. doi:10.1074/jbc.M401399200. PMID 15126504.
Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, et al. (2004). "Loss of WWOX expression in gastric carcinoma". Clinical Cancer Research. 10 (9): 3053–3058. doi:10.1158/1078-0432.CCR-03-0594. PMID 15131042.
Park SW, Ludes-Meyers J, Zimonjic DB, Durkin ME, Popescu NC, Aldaz CM (2004). "Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma". British Journal of Cancer. 91 (4): 753–759. doi:10.1038/sj.bjc.6602023. PMC 2364795. PMID 15266310.

This article on a gene on human chromosome 16 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000186153 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000004637 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Bednarek_2000-5] Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM (May 2000). "WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24.1, a region frequently affected in breast cancer". Cancer Research. 60 (8): 2140–2145. PMID 10786676.

[Ried_2000-6] Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, et al. (September 2000). "Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells". Human Molecular Genetics. 9 (11): 1651–1663. doi:10.1093/hmg/9.11.1651. PMID 10861292.

[Persson_2009-7] Persson B, Kallberg Y, Bray JE, Bruford E, Dellaporta SL, Favia AD, et al. (February 2009). "The SDR (Short-Chain Dehydrogenase/Reductase and Related Enzymes) Nomenclature Initiative". Chemico-Biological Interactions. 178 (1–3): 94–98. doi:10.1016/j.cbi.2008.10.040. PMC 2896744. PMID 19027726.

[entrez-8] "Entrez Gene: WWOX WW domain containing oxidoreductase".

[Pollard2006-9] Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, et al. (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans". Nature. 443 (7108): 167–172. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. hdl:2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/51805. PMID 16915236. S2CID 18107797. supplement

[Chang_2001-10] Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, et al. (February 2001). "Hyaluronidase induction of a WW domain-containing oxidoreductase that enhances tumor necrosis factor cytotoxicity". The Journal of Biological Chemistry. 276 (5): 3361–3370. doi:10.1074/jbc.M007140200. PMID 11058590.

[Mahajan_2005-11] Mahajan NP, Whang YE, Mohler JL, Earp HS (November 2005). "Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox". Cancer Research. 65 (22): 10514–10523. doi:10.1158/0008-5472.can-05-1127. PMID 16288044.

[12] Piard J, Hawkes L, Milh M, Villard L, Borgatti R, Romaniello R, et al. (June 2019). "The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature". Genetics in Medicine. 21 (6): 1308–1318. doi:10.1038/s41436-018-0339-3. PMC 6752669. PMID 30356099.

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