ZIC3

ZIC3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2EJ4, 2RPC
Identifiers
Aliases	ZIC3, HTX, HTX1, VACTERLX, ZNF203, Zic family member 3
External IDs	MGI: 106676 HomoloGene: 55742 GeneCards: ZIC3
Gene ontology Molecular function • protein binding • DNA binding • nucleic acid binding • sequence-specific DNA binding • metal ion binding • transcription factor activity, sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding Cellular component • nucleoplasm • cytoplasm • nucleus Biological process • determination of left/right symmetry • somatic stem cell population maintenance • determination of pancreatic left/right asymmetry • nervous system development • determination of digestive tract left/right asymmetry • multicellular organism development • heart looping • cell differentiation • regulation of transcription, DNA-templated • anterior/posterior pattern specification • determination of liver left/right asymmetry • pattern specification process • transcription, DNA-templated • lung development • determination of left/right asymmetry in nervous system • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7547	22773
Ensembl	ENSG00000156925	ENSMUSG00000067860
UniProt	O60481	Q62521
RefSeq (mRNA)	NM_003413	NM_009575
RefSeq (protein)	NP_003404.1	NP_033601.2
Location (UCSC)	Chr X: 137.57 – 137.58 Mb	Chr X: 58.02 – 58.04 Mb
PubMed search	[1]	[2]
Wikidata

ZIC3 is a member of the Zinc finger of the cerebellum (ZIC) protein family.^[3][4]

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,^[5] 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.^[6] 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.^[7]

ZIC3 is also of particular interest as it has been shown to be required for maintenance of embryonic stem cell pluripotency.^[8]

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.^[9] 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.^[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.

References

Further reading