ZIC2

Protein-coding gene in the species Homo sapiens
ZIC2
Identifiers
AliasesZIC2, HPE5, Zic family member 2
External IDsOMIM: 603073; MGI: 106679; HomoloGene: 5171; GeneCards: ZIC2; OMA:ZIC2 - orthologs
Gene location (Human)
Chromosome 13 (human)
Chr.Chromosome 13 (human)[1]
Chromosome 13 (human)
Genomic location for ZIC2
Genomic location for ZIC2
Band13q32.3Start99,981,784 bp[1]
End99,986,765 bp[1]
Gene location (Mouse)
Chromosome 14 (mouse)
Chr.Chromosome 14 (mouse)[2]
Chromosome 14 (mouse)
Genomic location for ZIC2
Genomic location for ZIC2
Band14 E5|14 65.97 cMStart122,712,847 bp[2]
End122,717,264 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • cerebellar cortex

  • cerebellar hemisphere

  • right hemisphere of cerebellum

  • pons

  • cerebellar vermis

  • ventricular zone

  • trigeminal ganglion

  • endothelial cell

  • lateral nuclear group of thalamus

  • ganglionic eminence
Top expressed in
  • cerebellar cortex

  • Neural groove

  • neural fold

  • stria vascularis

  • epiblast

  • lumbar subsegment of spinal cord

  • ventricular zone

  • tail of embryo

  • urethra

  • male urethra
More reference expression data
BioGPS
More reference expression data
Gene ontology
Molecular function
  • DNA-binding transcription factor activity
  • DNA binding
  • chromatin DNA binding
  • metal ion binding
  • nucleic acid binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding
  • DNA-binding transcription activator activity, RNA polymerase II-specific
Cellular component
  • cytoplasm
  • nucleus
  • nuclear body
Biological process
  • positive regulation of transcription, DNA-templated
  • multicellular organism development
  • cell differentiation
  • brain development
  • positive regulation of DNA-binding transcription factor activity
  • negative regulation of transcription, DNA-templated
  • regulation of transcription, DNA-templated
  • transcription, DNA-templated
  • visual perception
  • nervous system development
  • regulation of transcription by RNA polymerase II
  • positive regulation of transcription by RNA polymerase II
  • central nervous system development
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

7546

22772

Ensembl

ENSG00000043355

ENSMUSG00000061524

UniProt

O95409

Q62520

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

  • Barratt KS, Arkell R (2018). "ZIC2 in Holoprosencephaly". Zic family. Advances in Experimental Medicine and Biology. Vol. 1046. pp. 269–299. doi:10.1007/978-981-10-7311-3_14. ISBN 978-981-10-7310-6. PMID 29442327.
  • 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. hdl:1885/65873. PMID 23443491. S2CID 8660667.
  • Brown LY, Odent S, David V, Blayau M, Dubourg C, Apacik C, Delgado MA, Hall BD, Reynolds JF, Sommer A, Wieczorek D, Brown SA, Muenke M (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, Bendavid C, Blayau M, Le Duff F, Durou MR, Odent S, David V (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. S2CID 34076824.


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