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FLASH GENE

Symbol

NR2F2

contributors: mct/npt - updated : 28-11-2023

HGNC name	nuclear receptor subfamily 2, group F, member 2
HGNC id	7976

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_021005 3 - 5110 NP_066285 - 414 - 2013 23458092 NM_001145157 3 - 3962 NP_001138629 - 261 - 2013 23458092 NM_001145156 3 - 3501 NP_001138628 - 261 - 2013 23458092 NM_001145155 3 - 3869 NP_001138627 - 281 - 2013 23458092 variant 2 lacking a DNA-binding domain negatively regulates the function of NR2F2 by inhibiting its binding to DNA to decrease CYP7A1 expression

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       moderately   vessels       moderately Digestive liver         Endocrine adrenal gland         Lymphoid/Immune spleen       highly Reproductive female system ovary       Homo sapiens   male system testis       Urinary bladder       highly   kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Lymphoid

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a N terminal modulating domain
	a central bipartite zinc finger, DNA binding domain
	a C terminal ligand domain, strongly repressing NTS transcription, whereas the N-terminal domain antagonizes this repressive effect (MID: 21030593)

mono polymer

homomer , dimer

HOMOLOGY

interspecies	ortholog to rattus Nr2f2
	ortholog to murine Nr2f2
	homolog to C. elegans unc-55

Homologene

FAMILY	small family of the steroid/thyroid hormone receptor nuclear superfamily of transcription factors
	NR2 subfamily

CATEGORY

regulatory , receptor nuclear membrane serine/threonine

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	may be required for angiogenesis and heart developpment
	negative post transcriptional regulator of MYOD1 function
	involved in the regulation of the apolipoprotein A-I gene transcription
	playing a critical role in repressing Notch signaling to maintain vein identity
	having an important maternal function in placental formation and involved in trophoblast giant cells differentiation
	plays important roles in the regulation of the function of PROX1, and regulates the functions of PROX1 in lymphatic endothelial cells through direct interaction (Yamazaki 2009)
	functions as a coregulator of PROX1 to control several lineage-specific genes including FLT4, FGFR3, and NRP1 and is required along with PROX1 to maintain lymphatic endothelial cells phenotype (Lee 2009)
	directly regulates the transcription of angiopoietin-1 in pericytes to enhance neoangiogenesis (Qin 2010)
	controls angiopoietin-1/Tie2 signaling to regulate tumor angiogenesis (Qin 2010)
	important for both initiation and continued expansion and maintenance of angiogenic process (Qin 2010)
	with NR2F1 play roles in amacrine cell differentiation (Inoue 2010)
	involved in the organogenesis of the stomach, limbs, skeletal muscles, and heart
	is required for the specification of the metanephric mesenchyme
	plays a central role in the specification of metanephric fate and in the maintenance of metanephric mesenchyme proliferation and survival by acting as a crucial regulator of EYA1 and WT1 expression
	pleiotropic developmental transcription factor
	play a key role in integrating genetic and environmental risk factors for abnormal cardiac development
	is a human "pro-ovary" and "anti-testis" sex-determining factor in female gonads
	may be required to establish ovary identity during early human gonad development by the repression of genes involved in testis determination
	acts both positively and negatively to modulate the expression of genes involved in sex determination in other cellular and organ contexts
	plays an important role in angiogenesis and heart development
	transcription factor essential for proper cardiovascular development
	NR2F2 plays likely a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT
	BCL11A is essential for Schwann cell activation and peripheral nerve regeneration

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

lipid/lipoprotein

signaling

signal transduction

a component

INTERACTION

DNA	binding to DNA site A

RNA

small molecule	metal binding,
	Zn2+

protein	functions as a transcriptional repressor of pro-testis genes
	directly regulates the expression of both EYA1 and WT1 in the metanephric mesenchyme
	interacts with SMAD4 to modulate TGFB1 signalling
	FGF2 is an extracellular inducer of NR2F2 expression and may suppress the osteogenic potential of mesenchymal cells by inducing NR2F2 expression prior to the onset of osteogenic differentiation
	TEK is essential for venous specification and maintenance via AKT1 mediated stabilization of NR2F2
	cooperation between the orphan nuclear receptors NR2F2 and NR5A1 in the regulation of INSL3 gene expression in Leydig cells
	BCL11A may mediate Schwann cell activity through binding to the promoter of nuclear receptor subfamily 2 group F member 2 (NR2F2) and regulating NR2F2 expression

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

DEL15QD , DIH1 , SRXX5

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --low   significantly impaired adult neoangiogenesis (Qin 2010) tumoral       gain of function upregulated in metastatic prostate cancer, and its higher expression correlated with a worse clinical outcome constitutional       loss of function mutation is responsible for congenital bicuspid aortic valve

Susceptibility

to nonsyndromic atrioventricular septal defects (AVSDs)

Variant & Polymorphism other	variants in NR2F2 probably contribute to AVSDs and other CHDs during human development

Candidate gene	for heart defects in del 15q patients
	for isolated congenital diaphragmatic hernia
Marker
Therapy target
	System Type Disorder Pubmed cancer     inhibition of NR2F2 may offer a therapeutic approach for anticancer intervention cancer metastases   . inhibition of NR2F2 suppresses metastases of mammary tumors to the lung cancer reproductive prostate is a potential drug target for the intervention of metastatic human prostate cancer

ANIMAL & CELL MODELS

	decreased dosage of Nr2f2 in mice has been shown to result in abnormal development of atrioventricular septa
	mice lacking Coup-tf2 die around E10 due to defects of angiogenesis and heart development