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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003413 3 - 3939 NP_003404 - 467 - 2006 16631752

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Visual eye retina       Homo sapiens Fetal

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