ZIC5

ZIC5
Identifiers
Aliases	ZIC5, Zic family member 5
External IDs	OMIM: 617896 MGI: 1929518 HomoloGene: 11301 GeneCards: ZIC5
Gene location (Human)
Chr.	Chromosome 13 (human)[1]
End	99,971,767 bp[1]
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)[2]
End	122,703,089 bp[2]
RNA expression pattern
	Top expressed in
	ganglionic eminence; ; sural nerve; ; cerebellar vermis; ; Brodmann area 9; ; cingulate gyrus; ; amygdala; ; prefrontal cortex; ; hippocampus proper; ; putamen; ; hypothalamus;
	Top expressed in
	pineal gland; ; habenula; ; stria vascularis; ; otolith organ; ; utricle; ; cerebellar vermis; ; ciliary body; ; cochlea; ; calvaria; ; hand;
	More reference expression data
	n/a
Gene ontology
Molecular function	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;
Cellular component	nucleus;
Biological process	multicellular organism development; cell differentiation; nervous system development; regulation of transcription by RNA polymerase II; central nervous system development;
	Sources:Amigo / QuickGO
Orthologs
	85416
	65100
	ENSG00000139800
	ENSMUSG00000041703
	Q96T25
	Q7TQ40
	NM_033132
	NM_022987
	NP_149123
	NP_075363
	Wikidata
View/Edit Human	View/Edit Mouse

ZIC5 is a member of the Zinc finger of the cerebellum (ZIC) protein family.[5] ZIC5 is located on chromosome 13 in a divergently transcribed gene pair with the closely related gene ZIC2.[6] It has been suggested that this tandem arrangement allows ZIC2 and ZIC5 to share regulatory elements and causes the two genes to have very similar expression patterns.[6]

ZIC5 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and regulate transcription. Similar to other ZIC family members, ZIC5 is also able to interact with TCF proteins in order to inhibit canonical Wnt signalling. Mutation or loss of ZIC5 has not been associated with any congenital defects in humans. however, loss of Zic5 in mice causes a range of phenotypes including neural crest defects, neural tube defects, hydrocephaly and skeletal defects, indicating multiple functions during early development.[7][8] Experiments in Xenopus also support the idea that Zic5 can regulate formation of neural crest, suggesting this function is conserved across species.[9]

ZIC5 has recently been found to be regulated by the post-translational modification SUMOylation in order to alter the DNA and protein binding properties of ZIC5 to promote neural crest specification.[10] Several other genes involved in the specification of neural crest, including Pax6, Sox9 and Sox10, also been found to be regulated by the same postranslational modification, suggesting that SUMOylation may have a widespread role in formation of the neural crest.

References

GRCh38: Ensembl release 89: ENSG00000139800 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000041703 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
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.
Furushima, K; Murata, T; Matsuo, I; Aizawa, S (Nov 2000). "A new murine zinc finger gene, Opr". Mechanisms of Development. 98 (1–2): 161–164. doi:10.1016/S0925-4773(00)00456-1. PMID 11044622.
Inoue, Takashi; Hatayama, Minoru; Tohmonda, Takahide; Itohara, Shigeyoshi; Aruga, Jun; Mikoshiba, Katsuhiko (June 2004). "Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives". Developmental Biology. 270 (1): 146–162. doi:10.1016/j.ydbio.2004.02.017. PMID 15136147.
Nakata, K; Koyabu, Y; Aruga, Y; Mikoshiba, K (Dec 2000). "A novel member of the Xenopus Zic family, Zic5, mediates neural crest development". Mechanisms of Development. 99 (1–2): 83–91. doi:10.1016/s0925-4773(00)00480-9. PMID 11091076.
Ali, Radiya; Bellchambers, Helen; Warr, Nicholas; Ahmed, Jehangir; Barratt, Kristen; Neill, Kieran; Diamand, Koula; Arkell, Ruth (March 2021). "WNT responsive SUMOylation of ZIC5 promotes murine neural crest cell development via multiple effects on transcription". Journal of Cell Science. 134 (9). doi:10.1242/jcs.256792. ISSN 0021-9533. PMID 33771929. S2CID 232376525.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000139800 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000041703 - 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.

[pmid22964024-5] 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.

[pmid23443491-6] 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.

[7] Furushima, K; Murata, T; Matsuo, I; Aizawa, S (Nov 2000). "A new murine zinc finger gene, Opr". Mechanisms of Development. 98 (1–2): 161–164. doi:10.1016/S0925-4773(00)00456-1. PMID 11044622.

[8] Inoue, Takashi; Hatayama, Minoru; Tohmonda, Takahide; Itohara, Shigeyoshi; Aruga, Jun; Mikoshiba, Katsuhiko (June 2004). "Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives". Developmental Biology. 270 (1): 146–162. doi:10.1016/j.ydbio.2004.02.017. PMID 15136147.

[9] Nakata, K; Koyabu, Y; Aruga, Y; Mikoshiba, K (Dec 2000). "A novel member of the Xenopus Zic family, Zic5, mediates neural crest development". Mechanisms of Development. 99 (1–2): 83–91. doi:10.1016/s0925-4773(00)00480-9. PMID 11091076.

[pmid33771929-10] Ali, Radiya; Bellchambers, Helen; Warr, Nicholas; Ahmed, Jehangir; Barratt, Kristen; Neill, Kieran; Diamand, Koula; Arkell, Ruth (March 2021). "WNT responsive SUMOylation of ZIC5 promotes murine neural crest cell development via multiple effects on transcription". Journal of Cell Science. 134 (9). doi:10.1242/jcs.256792. ISSN 0021-9533. PMID 33771929. S2CID 232376525.