|Zic family member 2|
|Symbols||ZIC2 (; HPE5)|
|RNA expression pattern|
ZIC2 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and proteins. Correct function of these proteins in critical for early development, and as such mutations of the genes encoding these proteins is known to result in various congenital defects. For example, mutation of ZIC2 is known to result in holoprosencephaly due to defect in the function of the organizer region (node), which leads to a defective anterior notochord (ANC). The ANC provides a maintenance signal to the Prechordal plate (PCP), thus a defective ANC results in degradation of the PCP, which is normally responsible for sending a shh signal to the developing forebrain resulting in the formation of the two hemispheres. Holoprosencephaly is the most common structural anomaly of the human forebrain.
A polyhistidine tract polymorphism in this gene may be associated with increased risk of neural tube defects (spina bifida). This gene is closely linked to a gene encoding ZIC5, a related family member on chromosome 13.
ZIC2 has recently been found to interact with TCF7L2, enabling it to act as a Wnt/β-catenin signalling inhibitor. Such a role is of critical importance, as not only is correct Wnt signalling critical for early development, Wnt signalling has also been found to be upregulated to several cancers. ZIC2 has also been shown to interact with GLI3.
- Ali RG, Bellchambers HM, Arkell RM (November 2012). "Zinc finger of the cerebellum (Zic): Transcription factors and co-factors". Int J Biochem Cell Bio 22 (11): 2065–8. doi:10.1016/j.biocel.2012.08.012. PMID 22964024.
- "Entrez Gene: ZIC2 Zic family member 2 (odd-paired homolog, Drosophila)".
- Warr N, Powles-Glover N, Chappell A, Robson J, Norris D, Arkell RM (October 2008). "Zic2-associated holoprosencephaly is caused by a transient defect in the organizer region during gastrulation". Hum Mol Genet 17 (19): 2986–96. doi:10.1093/hmg/ddn197. PMID 18617531.
- Pourebrahim R, Houtmeyers R, Ghogomu S, Janssens S, Thelie A, Tran HT, Langenberg T, Vleminckx K, Bellefroid E, Cassiman JJ, Tejpar S. (October 2011). "Transcription factor Zic2 inhibits Wnt/β-catenin protein signaling.". J Biol Chem 286 (43): 37732–40. doi:10.1074/jbc.M111.242826. PMC 3199516. PMID 21908606.
- Fossat N, Jones V, Khoo PL, Bogani D, Hardy A, Steiner K, Mukhopadhyay M, Westphal H, Nolan PM, Arkell R, Tam PP. (February 2011). "Stringent requirement of a proper level of canonical WNT signalling activity for head formation in mouse embryo.". Development 138 (4): 667–76. doi:10.1242/dev.052803. PMID 21228006.
- Koyabu, Y; Nakata K, Mizugishi K, Aruga J, Mikoshiba K (March 2001). "Physical and functional interactions between Zic and Gli proteins". J. Biol. Chem. (United States) 276 (10): 6889–92. doi:10.1074/jbc.C000773200. ISSN 0021-9258. PMID 11238441.
- Houtmeyers R, Souopgui J, Tejpar S, Arkell R. (2013). "The ZIC gene family encodes multi-functional proteins essential for patterning and morphogenesis.". Cell Mol Life Sci. 70 (20): 3791–811. doi:10.1007/s00018-013-1285-5. PMID 23443491.
- Brown S, Gersen S, Anyane-Yeboa K, Warburton D (1993). "Preliminary definition of a "critical region" of chromosome 13 in q32: report of 14 cases with 13q deletions and review of the literature.". Am. J. Med. Genet. 45 (1): 52–9. doi:10.1002/ajmg.1320450115. PMID 8418661.
- Brown LY, Odent S, David V et al. (2001). "Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination". Hum. Mol. Genet. 10 (8): 791–6. doi:10.1093/hmg/10.8.791. PMID 11285244.
- Dubourg C, Lazaro L, Pasquier L et al. (2004). "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: Mutation review and genotype-phenotype correlations". Hum. Mutat. 24 (1): 43–51. doi:10.1002/humu.20056. PMID 15221788.
- Brown L, Paraso M, Arkell R, Brown S (2005). "In vitro analysis of partial loss-of-function ZIC2 mutations in holoprosencephaly: alanine tract expansion modulates DNA binding and transactivation". Hum. Mol. Genet. 14 (3): 411–20. doi:10.1093/hmg/ddi037. PMID 15590697.
- Ishiguro A, Ideta M, Mikoshiba K et al. (2007). "ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A". J. Biol. Chem. 282 (13): 9983–95. doi:10.1074/jbc.M610821200. PMID 17251188.
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