Recombinant Human Zinc finger protein ZIC 2 (ZIC2), partial

Function

Acts as a transcriptional activator or repressor. Plays important roles in the early stage of organogenesis of the CNS. Activates the transcription of the serotonin transporter SERT in uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye-specific projections in primary visual targets. Its transcriptional activity is repressed by MDFIC. Involved in the formation of the ipsilateral retinal projection at the optic chiasm midline. Drives the expression of EPHB1 on ipsilaterally projecting growth cones. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Associates to the basal SERT promoter region from ventrotemporal retinal segments of retinal embryos

Subcellular Location

Nucleus; Cytoplasm

Disease Association

Holoprosencephaly 5 (HPE5) : A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. HPE5 inheritance is autosomal dominant. [The disease is caused by variants affecting the gene represented in this entry]

Subunit

Interacts with RNF180. Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity. Interacts with GLI1 and GLI2 (By similarity). Interacts (via C2H2-type domain 3) with DHX9 (PubMed:17251188)

• Brown S.A. et al. Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. — Nat. Genet. (1998)
• Yang Y. et al. ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene. — J. Biol. Chem. (2000)
• Dunham A. et al. The DNA sequence and analysis of human chromosome 13. — Nature (2004)
• Ishiguro A. et al. ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A. — J. Biol. Chem. (2007)
• Rigbolt K.T. et al. System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. — Sci. Signal. (2011)
• Hendriks I.A. et al. Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. — Nat. Struct. Mol. Biol. (2017)
• Brown L.Y. et al. Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination. — Hum. Mol. Genet. (2001)
• Dubourg C. et al. Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations. — Hum. Mutat. (2004)