Zinc finger protein ZIC2 is a protein that in humans is encoded by the ZIC2gene.[5][6] ZIC2 is a member of the Zinc finger of the cerebellum (ZIC) protein family.[7]
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 significanceedit
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]
Interactionsedit
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]
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000043355 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000061524 - 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.
^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.
^ abc"Entrez Gene: ZIC2 Zic family member 2 (odd-paired homolog, Drosophila)".
^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.
^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.
^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. PMID 24585447.
^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.
^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 readingedit
Barratt KS, Arkell R (2018). "ZIC2 in Holoprosencephaly". Adv Exp Med Biol. Advances in Experimental Medicine and Biology. 1046: 269–299. doi:10.1007/978-981-10-7311-3_14. ISBN978-981-10-7310-6. 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.
This article on a gene on human chromosome 13 is a stub. You can help Wikipedia by expanding it.
zic2, zinc, finger, protein, protein, that, humans, encoded, gene, member, zinc, finger, cerebellum, protein, family, identifiersaliases, hpe5, family, member, 2external, idsomim, 603073, 106679, homologene, 5171, genecards, gene, location, human, chromosome, . 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 ZIC2IdentifiersAliasesZIC2 HPE5 Zic family member 2External IDsOMIM 603073 MGI 106679 HomoloGene 5171 GeneCards ZIC2Gene location Human Chr Chromosome 13 human 1 Band13q32 3Start99 981 784 bp 1 End99 986 765 bp 1 Gene location Mouse Chr Chromosome 14 mouse 2 Band14 E5 14 65 97 cMStart122 712 847 bp 2 End122 717 264 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incerebellar cortexcerebellar hemisphereponscerebellar vermistrigeminal ganglionendothelial cellganglionic eminencehippocampus properpostcentral gyrusBrodmann area 23Top expressed incerebellar cortexstria vascularisurethramale urethralenssuperior frontal gyruspineal glandsclerotomeentorhinal cortexolfactory bulbMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionDNA 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 specificCellular componentcytoplasm nucleus nuclear bodyBiological processpositive 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 developmentSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez754622772EnsemblENSG00000043355ENSMUSG00000061524UniProtO95409Q62520RefSeq mRNA NM 007129NM 009574RefSeq protein NP 009060NP 033600Location UCSC Chr 13 99 98 99 99 MbChr 14 122 71 122 72 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 Interactions 4 References 5 Further readingFunction editZIC2 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 editCorrect 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 editZIC2 has recently been found to interact with TCF7L2 enabling it to act as a Wnt b 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 edit a b c GRCh38 Ensembl release 89 ENSG00000043355 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000061524 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 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 a b c Entrez Gene ZIC2 Zic family member 2 odd paired homolog Drosophila 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 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 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 PMID 24585447 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 b catenin protein signaling J Biol Chem 286 43 37732 40 doi 10 1074 jbc M111 242826 PMC 3199516 PMID 21908606 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 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 editBarratt KS Arkell R 2018 ZIC2 in Holoprosencephaly Adv Exp Med Biol Advances in Experimental Medicine and Biology 1046 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 nbsp This article on a gene on human chromosome 13 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title ZIC2 amp oldid 1172773795, wikipedia, wiki, book, books, library,
