ZIC2

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ZIC2
Identifiers
AliasesZIC2, HPE5, Zic family member 2
External IDsOMIM: 603073 MGI: 106679 HomoloGene: 5171 GeneCards: ZIC2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_007129

NM_009574

RefSeq (protein)

NP_009060

NP_033600

Location (UCSC)Chr 13: 99.98 – 99.99 MbChr 14: 122.71 – 122.72 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Zinc finger protein ZIC2 is a protein that in humans is encoded by the ZIC2 gene.[5][6] ZIC2 is a member of the Zinc finger of the cerebellum (ZIC) protein family.[7]

Function

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.[6]

Clinical significance

Correct function of these proteins is 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.[8] Holoprosencephaly is the most common structural anomaly of the human forebrain.

Recently ZIC2 has also been shown to be critical for establishment of the left-right axis, thus loss of ZIC2 function can result in defects in heart formation.[9] Another member of the ZIC family, ZIC3, has previously been linked to establishment of the left-right axis.

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.[6]

Interactions

ZIC2 has recently been found to interact with TCF7L2, enabling it to act as a Wnt/β-catenin signalling inhibitor.[10] Such a role is of critical importance, as not only is correct Wnt signalling critical for early development,[11] Wnt signalling has also been found to be upregulated to several cancers. ZIC2 has also been shown to interact with GLI3.[12]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000043355 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000061524 - 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.
  5. ^ Brown SA, Warburton D, Brown LY, Yu CY, Roeder ER, Stengel-Rutkowski S, Hennekam RC, Muenke M (1998). "Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired". Nat Genet. 20 (2): 180–3. doi:10.1038/2484. PMID 9771712. S2CID 24757246.
  6. ^ a b c "Entrez Gene: ZIC2 Zic family member 2 (odd-paired homolog, Drosophila)".
  7. ^ Ali RG, Bellchambers HM, Arkell RM (November 2012). "Zinc finger of the cerebellum (Zic): Transcription factors and co-factors". Int J Biochem Cell Biol. 44 (11): 2065–8. doi:10.1016/j.biocel.2012.08.012. PMID 22964024.
  8. ^ 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.
  9. ^ Barratt KS, Glanville-Jones HC, Arkell RM (Jun 2013). "The Zic2 gene directs the formation and function of node cilia to control cardiac situs". Genesis. 52 (6): 626–35. doi:10.1002/dvg.22767. hdl:1885/66428. PMID 24585447.
  10. ^ 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.
  11. ^ 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. hdl:1885/66666. PMID 21228006.
  12. ^ Koyabu Y, Nakata K, Mizugishi K, Aruga J, Mikoshiba K (March 2001). "Physical and functional interactions between Zic and Gli proteins". J. Biol. Chem. 276 (10): 6889–92. doi:10.1074/jbc.C000773200. PMID 11238441.

Further reading