zinc finger protein ZIC2; zinc finger protein of the cerebellum 2 (ZIC2)

Function

• transcriptional activator or transcriptional repressor
• roles in the early stage of organogenesis of the CNS
• activates 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
• role in formation of the ipsilateral retinal projection at the optic chiasm midline
• drives expression of EPHB1 on ipsilaterally projecting growth cones
• binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'
• associates with the basal SERT promoter region from ventrotemporal retinal segments of retinal embryos
• phosphorylated
• ubiquitinated by RNF180, leading to its degradation
• interacts with RNF180
• interacts (via the C2H2-type zinc finger domains 3, 4 & 5) with MDFIC
  • interaction reduces its transcriptional activity
• interacts with DHX9 (putative)

Structure

• the C2H2-type Zn+2 finger domains 3, 4 & 5 are necessary for transcription activation (putative)
• belongs to the GLI C2H2-type Zn+2-finger protein family
• contains 5 C2H2-type Zn+2 fingers

Compartment

• nucleus. cytoplasm (putative)
• localizes in the cytoplasm with MDFIC overexpression
• both phosphorylated & unphosphorylated forms are localized in the nucleus (putative)

Pathology

• defects in ZIC2 are a cause of holoprosencephaly type 5

Polymorphism

• the poly-His region between amino acids 231-239 of ZIC2 is polymorphic
  • the number of His can vary from 8-12

More general terms

• zinc finger protein of the cerebellum (ZIC)
• nuclear protein
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=7546
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:7546
• OMIM: https://mirror.omim.org/entry/603073
• OMIM: https://mirror.omim.org/entry/609637
• UniProt: http://www.uniprot.org/uniprot/O95409.html