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FLASH GENE

Symbol

GATA6

contributors: mct - updated : 26-11-2014

HGNC name	GATA binding protein 6
HGNC id	4174

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ASD9 atrial septal defect 9 AVSD5 atrioventricular septal defect 5 OFTD cardiac outflow tract defects PACHD pancreatic agenesis and congenital heart defects
Location	18q11.2      Physical location : 19.749.415 - 19.782.227
Synonym name	transcription factor GATA-6
Synonym symbol(s)	GAT6

DNA

TYPE	functioning gene
STRUCTURE	33.01 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005257 7 - 3494 NP_005248 - 595 - 2008 18768929

EXPRESSION

Type

widely

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 Cardiovascular heart       highly Digestive intestine large intestine rectum   highly Homo sapiens   stomach         Endocrine adrenal gland cortex     highly Reproductive female system uterus cervix   highly   male system testis       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Epithelial absorptive excretory digestive epithelium (mucosa)     Homo sapiens Epithelial barrier lining neuroepithelium

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell Nervous astrocyte Nervous neuron Reproductive granulosa cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal, pregnancy

Text	developing heart

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two adjacent zinc finger of a distinctive form CXNCX(17) CNXC and associated basic domains, two tandem GATA zinc fingers
	a stretch of residues, 10 histidine, encoded by a CAX trinucleotide repeat
	two highly conserved zinc-finger DNA binding domains that interact with a canonical DNA motif (G/A)GATA(A/T)

HOMOLOGY

interspecies

homolog to murine Gata6

Homologene

FAMILY

GATA zinc finger transcription factor family

CATEGORY

motor/contractile , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	involved in regulating terminal differentiation and/or proliferation
	play critical roles in restricting cell lineage differentiation during development (primary function during cardiovascular development is to regulate morphogenetic patterning of the cardiac outflow tract and aortic arch)
	in human fetal testis, GATA6 is linked to the expression level of Bax and BCL2
	endodermal transcription factor having a protective function in lung epithelial cells exposed to P. aeruginosa
	play an important role in adrenal steroid biosynthesis
	may play a dominant role in cardiac outflow tract development, although it has been reported to have a redundant role with GATA4 during cardiogenesis
	essential for differentiation of visceral mesoderm and morphogenetic patterning of cardiac outflow tract and large arteries
	also plays a role in chondrogenesis and LGR5 is a potential direct target of GATA regulation in this process
	may regulate expression of the calreticulin gene during cardiac development
	promotes angiogenic function and survival in endothelial cells by suppression of TGFBR1)
	key role for the transcription factor GATA6 in human pancreatic development
	GATA4 and GATA6 are needed for normal ovarian function
	implicated in the development of multiple organ systems, including the biliary tract, gut, pituitary and thyroid, as well as the pancreas
	GATA4, GATA45, GATA6 are indispensable for the lineage-specific development and differentiation of cells of endodermal and mesodermal origin
	promotes cell survival by regulating endoderm expression of BMP2 and basement membrane (BM)during embryonic epithelial morphogenesis
	in the colorectal epithelium, directs cell proliferation, differentiation and apoptosis

CELLULAR PROCESS	cell life, differentiation
	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding to GATA sequence

RNA

small molecule

protein	inducing DAB2 in the visceral endoderm
	regulating neurovascular guiding molecule semaphorin 3C (SEMA3C) and its receptor plexin A2 (SEMA3C and PLXNA2 are directly regulated by GATA6 through consensus binding sites on their enhancer elements and GATA6 mutations disturbs semaphorin-plexin signaling to varying degrees, resulting in abnormal development of the cardiac outflow tract)
	interacting with AQP5 (transcriptional activation of AQP5 by GATA6, mediated at least in part through cooperative interactions with Sp1 occurring at the proximal promoter)
	WNT2 is a direct downstream target of GATA6 during early cardiogenesis
	target of LGR5 regulation in differentiating embryonal carcinoma cell
	with MECOM, are new regulators of the calreticulin gene (antagonistic role between both GATA6 and MECOM)
	transcriptional repressor of TNC gene expression in fibroblasts
	GATA5 interacts with GATA4 and GATA6 in outflow tract development
	likely that the JNK activated by anisomycin may stimulate not only the nuclear export of GATA6 through XPO1 but also the degradation of GATA6 by cytoplasmic proteasomes
	BMI1 interacts with GATA6 in a Ring finger-dependent manner to confer protection against GATA6 ubiquitination and proteasomal degradation
	AGT promotes apoptosis in intestinal epithelial cells through GATA6 and the Bax pathway in an AT2 receptor-dependent manner
	HMGA2 directly regulates GATA6 and thereby modulates FZD2 expression

cell & other

REGULATION

repressed by

LMCD1

ASSOCIATED DISORDERS

corresponding disease(s)

OFTD , AVSD5 , ASD9 , PACHD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOH     in malignant astrocytoma, high grade tumoral   amplification --over   amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer constitutional germinal mutation       genetic cause of CHD through disruption of its direct regulation of semaphorin-plexin signaling involving the cardiac neural crest in the pathogenesis of cardiac outflow tract defects constitutional germinal mutation     loss of function in 56p100 individuals with pancreatic agenesis tumoral     --other   aberrant expression of GATA6 correlates with poor prognosis and liver metastasis in colorectal cancer tumoral     --over   in esophageal adenocarcinomas (EAC) constitutional     --over   hypomethylation is associated with overexpression of PLS3, GATA6, and TWIST1 in the Sezary Syndrome

Susceptibility

Variant & Polymorphism

Candidate gene	candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies
Marker
Therapy target
	System Type Disorder Pubmed cancer digestive pancreas RNA interference approach against GATA6 may be an effective therapeutic approach for treatment of pancreatic cancer (PMID: 23832791) cancer digestive oesophagus therapeutic deprivation of GATA6 in GATA6-amplified esophageal adenocarcinomas (EAC) patients may improve patient survival

ANIMAL & CELL MODELS

	regulating HNF, required for differentiation of visceral endoderm in mouse embryo
	Gata6(+/-)Gata5(+/-) mutant embryos have double outlet right ventricles (DORV) associated with subaortic VSDs
	simultaneous deletion of both murine Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis