Zinc finger E-box-binding homeobox 2 is aprotein that in humans is encoded by theZEB2gene.[5] The ZEB2 protein is atranscription factor that plays a role in thetransforming growth factor β (TGFβ) signaling pathways that are essential during early fetal development.[6]
ZEB2 (previously also known as SMADIP1, SIP1) and its mammalian paralogZEB1 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB2 protein has 8 zinc fingers and 1 homeodomain.[7] The structure of the homeodomain shown on the right.
ZEB2 interacts with receptor-mediated, activated full-lengthSMADs.[5] The activation of TGFβ receptors brings about the phosphorylation of intracellular effector molecules, R-SMADs. ZEB2 is an R-SMAD-binding protein and acts as a transcriptional corepressor. It is involved in the timing of the conversion ofneuroepithelial cells intoradial glial cells in early development, a mechanism thought to allow for the large differences inbrain size between humans and other mammals.[8]
Mutations in theZEB2 gene are associated with theMowat–Wilson syndrome. This disease exhibitsmutations and even complete deletions of theZEB2 gene. Mutations of the gene can cause the gene to produce nonfunctional ZEB2 proteins or inactivate the function of the gene as a whole. These deficits of ZEB2 protein interfere with the development of many organs. Many of the symptoms can be explained by the irregular development of the structures from the neural crest.[9]
Hirschsprung's disease also has many symptoms that can be explained by lack of ZEB2 during development of the digestive tract nerves. This disease causes severe constipation and enlargement of the colon.[10]
The risk of hepatocellular carcinoma and cirrhosis in chronichepatitis B has been reported to be associated with asingle-nucleotide polymorphism in the promoter region ofZEB2, designated rs3806475, under a recessive model of inheritance.[11]
^Bassez G, Camand OJ, Cacheux V, Kobetz A, Dastot-Le Moal F, Marchant D, et al. (March 2004). "Pleiotropic and diverse expression of ZFHX1B gene transcripts during mouse and human development supports the various clinical manifestations of the "Mowat-Wilson" syndrome".Neurobiology of Disease.15 (2):240–50.doi:10.1016/j.nbd.2003.10.004.PMID15006694.S2CID25770329.
^Dastot-Le Moal F, Wilson M, Mowat D, Collot N, Niel F, Goossens M (April 2007). "ZFHX1B mutations in patients with Mowat-Wilson syndrome".Human Mutation.28 (4):313–21.doi:10.1002/humu.20452.PMID17203459.S2CID37981110.
^Saunders CJ, Zhao W, Ardinger HH (November 2009). "Comprehensive ZEB2 gene analysis for Mowat-Wilson syndrome in a North American cohort: a suggested approach to molecular diagnostics".American Journal of Medical Genetics Part A.149A (11):2527–31.doi:10.1002/ajmg.a.33067.PMID19842203.S2CID22472646.
Ueki N, Oda T, Kondo M, Yano K, Noguchi T, Muramatsu M (December 1998). "Selection system for genes encoding nuclear-targeted proteins".Nature Biotechnology.16 (13):1338–42.doi:10.1038/4315.PMID9853615.S2CID20001769.
Wakamatsu N, Yamada Y, Yamada K, Ono T, Nomura N, Taniguchi H, et al. (April 2001). "Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease".Nature Genetics.27 (4):369–70.doi:10.1038/86860.PMID11279515.S2CID39070888.
Nagaya M, Kato J, Niimi N, Tanaka S, Wakamatsu N (August 2002). "Clinical features of a form of Hirschsprung's disease caused by a novel genetic abnormality".Journal of Pediatric Surgery.37 (8):1117–22.doi:10.1053/jpsu.2002.34455.PMID12149685.
Yoneda M, Fujita T, Yamada Y, Yamada K, Fujii A, Inagaki T, et al. (November 2002). "Late infantile Hirschsprung disease-mental retardation syndrome with a 3-bp deletion in ZFHX1B".Neurology.59 (10):1637–40.doi:10.1212/01.wnl.0000034842.78350.4e.PMID12451214.S2CID34389990.
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