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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
Corresponding disease
DEL15QD chromosome 15q distal deletion
DIH1 congenital diaphragmatic hernia and 15q26.1-26.2 deletion
SRXX5 46XX sex reversal 5
Location 15q26.2      Physical location : 96.869.156 - 96.883.490
Synonym name
  • apolipoprotein regulatory protein 1
  • transcription factor COUP 2 (chicken ovalbumin upstream promoter 2,
    • apolipoprotein regulatory protein)
  • ADP-ribosylation factor related protein 1
  • apolipoprotein AI regulatory protein 1
  • chicken ovalbumin upstream promoter transcription factor II
    • Synonym symbol(s) ARP1, TFCOUP2, COUPTF2, SVP40, COUP-TFII, COUPTFB, ARP-1, NF-E3, SRXX5, SVP40,
    DNA
    TYPE functioning gene
    STRUCTURE 14.34 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 - 5110 - 414 - 2013 23458092
    3 - 3962 - 261 - 2013 23458092
    3 - 3501 - 261 - 2013 23458092
    3 - 3869 - 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)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
     vessels   moderately
    Digestiveliver    
    Endocrineadrenal gland    
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemovary    Homo sapiens
     male systemtestis   
    Urinarybladder   highly
     kidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    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)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein 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
    SystemTypeDisorderPubmed
    cancer  
    inhibition of NR2F2 may offer a therapeutic approach for anticancer intervention
    cancermetastases 
    . inhibition of NR2F2 suppresses metastases of mammary tumors to the lung
    cancerreproductiveprostate
    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