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FLASH GENE
Symbol ZIC3 contributors: mct/pgu - updated : 27-02-2013
HGNC name Zic family member 3 heterotaxy 1 (odd-paired homolog, Drosophila)
HGNC id 12874
Corresponding disease
HTX1 abnormal left-right axis with visceral heterotaxy (situs ambiguus), 1
VACTERLX X-linked VACTERL syndrome with or without hydrocephalus
Location Xq26.3      Physical location : 136.648.345 - 136.654.257
Synonym name
  • zinc finger protein of the cerebellum 3
  • zinc finger protein 203
    • Synonym symbol(s) HTX, HTX1, ZNF203, VACTERLX
    DNA
    TYPE functioning gene
    STRUCTURE 5.91 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 3939 - 467 - 2006 16631752
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Visualeyeretina    Homo sapiensFetal
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text
  • primitive streak, heart tissues, stem cells
  • in embryonic retina
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • five C2H2 zinc fingers in a domain homolog to Drosophila pair-rule gene Opa (odd paired), and required for GLI-consensus site DNA binding and GLI protein interaction
  • two nuclear localization signals
  • also containing a stretch of alanine, GCC repeat
  • a GLI interacting domain required for transport to the nucleus
    • HOMOLOGY
    interspecies homolog to murine Zic
    homolog to Drosophila segmentation gene odd paired
    Homologene
    FAMILY
  • GLI C2H2-type zinc-finger protein family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    text ZIC1/ZIC2/ZIC3 proteins were translocated to the cytoplasmic compartment in the presence of MDFI
    basic FUNCTION
  • may be functioning as a transcription factor in the earliest stages of the left-right body axis formation
  • play a crucial role in early neural, neural crest and mesoderm development, as well as left-right axis formation
  • playing a role in regulating cardiac gene expression
  • playing a role in the maintenance of pluripotency in embryonic stem cells
  • may prevent endodermal marker expression through NANOG-regulated pathways
  • plays an important role in the maintenance of pluripotency by preventing endodermal lineage specification in embryonic stem cells
  • required for maintenance of ESC pluripotency
  • functions as a transcription factor in early stages of left-right body axis formation
  • ZIC1, ZIC2, ZIC3, are strongly expressed in immature retinal progenitor cells, and their roles in retinal differentiation and proliferation are suggested by gain-of-function analysis
  • similar activities of ZIC1, ZIC2, and ZIC3, suggesting that Zics are redundant in terms of retinal cell differentiation
  • primarily required in epiblast derivatives to affect left-right patterning and its expression in epiblast is necessary for proper transcriptional control of embryonic cardiac development
  • spatial requirement of ZIC3 during left-right patterning in the mammalian embryo
  • temporal and spatial requirement for ZIC3 in node morphogenesis, left-right patterning, and cardiac development, suggesting the possibility that a requirement for ZIC3 in node ultrastructure underlies its role in heterotaxy and laterality disorders
    • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulating small GTPase Rho
  • binding of the ZIC1/ZIC2/ZIC3 proteins to MDFI through their N-terminal regions
  • physically interacts with SRF and synergistically activates cardiac -actin and NPPA promoters with SRF
  • can bind to the GLI-consensus DNA binding site and function as a weak transcriptional coactivator
  • important pathway for regulation of NANOG expression in pluripotent ESCs through direct activation by ZIC3
    • cell & other
    REGULATION
    Other expression in pluripotent ES cells is also directly regulated by POU5F1, SOX2, and NANOG
    ASSOCIATED DISORDERS
    corresponding disease(s) HTX1 , VACTERLX
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Zic3 null mice recapitulate the human heterotaxy phenotype but also have early gastrulation defects, axial patterning defects, and neural tube defects complicating an assessment of the role of Zic3 in cardiac development