ZIC3

ZIC3 is a member of the Zinc finger of the cerebellum (ZIC) protein family.[5][6]

ZIC3
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesZIC3, HTX, HTX1, VACTERLX, ZNF203, Zic family member 3
External IDsOMIM: 300265 MGI: 106676 HomoloGene: 55742 GeneCards: ZIC3
Gene location (Human)
Chr.X chromosome (human)[1]
BandXq26.3Start137,566,127 bp[1]
End137,577,691 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

7547

22773

Ensembl

ENSG00000156925

ENSMUSG00000067860

UniProt

O60481

Q62521

RefSeq (mRNA)

NM_003413
NM_001330661

NM_009575

RefSeq (protein)

NP_001317590
NP_003404

NP_033601

Location (UCSC)Chr X: 137.57 – 137.58 MbChr X: 58.02 – 58.04 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

ZIC3 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 this protein family 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 ZIC3 is associated with heterotaxy,[7] that is thought to occur due to the role of ZIC3 in initial left-right symmetry formation, which involves the maintaining redistributed Nodal after the asymmetry of the embryo is initially broken.[8] Mutation of ZIC3 is also associated with various heart defects, such as heart looping, however these are thought to represent a mild form of heterotaxy. Mouse based studies have linked defective ZIC3 with neural tube defects (spina bifida) and skeletal defects.[9]

ZIC3 is also of particular interest as it has been shown to be required for maintenance of embryonic stem cell pluripotency.[10]

Involvement in Wnt signalling

ZIC2, another member of the ZIC family, has recently been found to interact with TCF7L2, enabling it to act as a Wnt/β-catenin signalling inhibitor.[11] Further experiments have indicated that human ZIC3 is also able to inhibit Wnt signalling and that the Zinc finger domains are absolutely critical for this role.[12] Such a role is of critical importance, as not only is correct Wnt signalling critical for early development,[13] Wnt signalling has also been found to be upregulated to several cancers.

References

  1. GRCh38: Ensembl release 89: ENSG00000156925 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000067860 - 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. 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.
  6. "Entrez Gene: ZIC3 Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila)".
  7. Ware SM, Peng J, Zhu L, Fernbach S, Colicos S, Casey B, Towbin J, Belmont JW (January 2004). "Identification and functional analysis of ZIC3 mutations in heterotaxy and related congenital heart defects". Am J Hum Genet. 74 (1): 93–105. doi:10.1086/380998. PMC 1181916. PMID 14681828.
  8. Ware SM, Harutyunyan KG, Belmont JW (January 2006). "Heart defects in X-linked heterotaxy: evidence for a genetic interaction of Zic3 with the nodal signaling pathway". Dev. Dyn. 235 (6): 1631–7. doi:10.1002/dvdy.20719. PMID 16496285.
  9. Purandare SM, Ware SM, Kwan KM, Gebbia M, Bassi MT, Deng JM, Vogel H, Behringer RR, Belmont JW, Casey B (May 2002). "A complex syndrome of left-right axis, central nervous system and axial skeleton defects in Zic3 mutant mice". Development. 129 (9): 2293–302. PMID 11959836.
  10. Lim LS, Hong FH, Kunarso G, Stanton LW (November 2010). "The pluripotency regulator Zic3 is a direct activator of the Nanog promoter in ESCs". Stem Cells. 28 (11): 1961–9. doi:10.1002/stem.527. PMID 20872845.
  11. 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.
  12. Ahmed JN, Ali RG, Warr N, Wilson HM, Bellchambers HM, Barratt KS, Thompson AJ, Arkell RM (May 2013). "A murine Zic3 transcript with a premature termination codon evades nonsense-mediated decay during axis formation". Dis. Models Mech. 6 (3): 755–67. doi:10.1242/dmm.011668. PMC 3634658. PMID 23471918.
  13. 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.

Further reading


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