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FLASH GENE

Symbol

GATA4

contributors: mct - updated : 04-01-2018

HGNC name	GATA binding protein 4
HGNC id	4173

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two adjacent zinc finger motif of a distinctive form CXNCX(17)CNXC, associated basic domains
	a stretch of alanine residues
	two transcriptional activation domains
	C terminal nuclear localization signal (NLS)

HOMOLOGY

interspecies

homolog to murine Gata4

Homologene

FAMILY

GATA zinc finger transcription factor family

CATEGORY

DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm

basic FUNCTION	involved in lineage determination
	regulating genes involved in embryogenesis and in myocardial differentiation and function, essential for functional separation of the four cardiac chambers)
	required during early cardiac development and essential factor for generation of the proepicardium
	important regulator of postnatal heart function and of the hypertrophic response of the heart to pathological stress, and protects the heart from load-induced failure
	potential tumor suppressor
	having a role in the transcriptional regulation of the IL5 gene in a circumstance where multiple members of the GATA-binding proteins are expressed
	positively regulates cardiac BCL2 gene expression
	potentially controling cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes (
	required for cyclin D2, cyclin A2, and Cdk4 expression in the right ventricle and Cyclin D2 and Cdk4 promoters are bound and activated by GATA4 via multiple consensus GATA binding sites in each gene proximal promoter (
	GATA4/5 exhibit tumor suppressive effects in colorectal cancer cells
	transcriptional inducer of CDKN2B, leading to the attenuation of cyclin D1
	negative regulator of astrocyte proliferation and growth
	in collaboration with NKX2-5, nuclear translocation in tissue-specific mesenchymal stem cells drives cardiac differentiation
	repressor role on ERBB2 gene expression plays a role in breast cancer
	essential for ventral body plan and formation of linear heart tube
	role for ZNF260 and GATA4 as mutual coactivators of a genetic program underlying cardiac hypertrophy
	key role of GATA4 in human testicular development
	GATA4 and SMAD4 cooperatively activated the ID2 promoter
	GATA4, GATA45, GATA6 are indispensable for the lineage-specific development and differentiation of cells of endodermal and mesodermal origin
	GATA4 and GATA6 are needed for normal ovarian function
	novel role for GATA4 and TAL1 to affect skeletal myogenic differentiation and EPO response via cross-talk with SIRT1
	negative effect of GATA4 in the reprogramming of somatic cells and potential role of GATA factors in the transcriptional networks that control cell lineage choices in the early embryo
	transcription factors NKX2-5 and GATA4 cooperatively regulate cardiac-specific expression of LRRC10
	essential role of the GATA4 protein in the ovarian morphogenetic program
	acting as a negative regulator in osteoblast differentiation by downregulation of RUNX2

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA	binding to GATA sequence

RNA

small molecule

protein	ZFPM2 (FOG2) (ZFPM2 in the early pulmonary mesenchyme participate in patterning the secondary bronchus of the accessory lobe)
	TBX5
	LHX9 gene represents the first direct target of the GATA4/ZFPM2 repressor complex in cardiac development
	cardiac expression of TNNT1 strictly depends on the physical interaction between GATA4-ZFPM2 in the myocardium of both atria and ventricles
	GATA4 may alter the activity of ZFPM2 by influencing its SUMOylation status
	GSN induces cardiomyocyte hypertrophy and NPPB expression via MAPK14 signaling and GATA4 transcriptional factor activation
	Cyclin D2 and CDK4 as direct transcriptional targets of GATA4
	cooperatively interacts with several proteins, including NR5A1 and FOG2, to regulate the expression of the sex-determining genes SRY (encoding sex-determining region Y), SOX9 (encoding SRY box 9), AMH (encoding anti-Müllerian hormone)
	binding of the N-terminal portion of SMAD4 to the second zinc-finger domain of GATA4 (genetically cooperate in the endocardium during atrioventricular valve formation)
	GATA5 interacts with GATA4 and GATA6 in outflow tract development
	PTK2 inhibition resulted in the loss of the GATA4 transcription factor required for TNF-induced VCAM1 production
	role for CCND2 in the postnatal heart as an effector of GATA4 in myocyte growth and survival
	LRRC10 is a transcriptional target of NKX2-5 and GATA4
	sex determination requires interaction between the transcription factor GATA4 and its cofactor ZFPM2
	interacted with DLX5 and subsequently decreased DLX5 binding activity to RUNX2 promoter region
	NR4A1 functionally interacts with NFATC3 and GATA4 and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy
	ZFPM2 is a multi-zinc finger protein that binds the transcriptional activator GATA4 and modulates GATA4-mediated regulation of target genes during heart development
	while GATA4 and SMARCD3 are key inducers of myocardial differentiation, TBX5 is essential for the ability of cardiac cells to contract
	GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells
	GATA4 and SOX11 are functional downstream targets of CBX7 in controlling axon regeneration

cell & other

REGULATION

induced by

TGFbeta, leading to the inhibition of astrocyte proliferation (Agnihotri 2009)

ASSOCIATED DISORDERS

corresponding disease(s)

DEL8P23 , DUP8P23 , ASD2 , CMD1NN , DIH2 , AVSD4

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in esophageal adenocarcinoma constitutional germinal mutation       in congenital heart defects(ASD, VSD) constitutional     --low   in heart failure, with mild baseline systolic and diastolic dysfunction tumoral     --low   in ovarian and gastric cancer tumoral         no expression in malignant astrocytoma cell lines constitutional     --over   enhanced expression in inflammatory Bowel disease tumoral       loss of function epigenetic inactivation by methylation of CpG islands is an early frequent event during gastric carcinogenesis significantly correlated with H. pylori infection constitutional germinal mutation       heterozygous missence mutation in a family with 46,XY DSD (disorder of sex development) and congenital heart disease ( constitutional   deletion     in congenital heart disease

Susceptibility

Variant & Polymorphism

Candidate gene	for heart defects in del 8p23 ;
	for isolated congenital diaphragmatic hernia, ;
Marker	GATA4 methylation in fecal DNA may be of interest for colorectal cancer detection
Therapy target

ANIMAL & CELL MODELS

	Gata4(+/-)Gata5(+/-) mutant embryos have double outlet right ventricles (DORV), large ventricular septal defects (VSD) as well as hypertrophied mitral and tricuspid valves and aortic stenosis
	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