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FLASH GENE
Symbol NR2E1 contributors: mct/npt/shn - updated : 17-05-2023
HGNC name nuclear receptor subfamily 2, group E, member 1
HGNC id 7973
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N terminal modulating domain
  • a central zinc finger DNA binding domain containing the discrete P and D boxes critical for target specificity
  • a C terminal ligand domain, including the T and A boxes, putatively involved in dimerization and sequence recognition, respectively
    • mono polymer monomer
    HOMOLOGY
    interspecies homolog to Drosophila tailless and Dsf
    ortholog to Nr2e1, Mus musculus
    homolog to C.elegans Nhr-67 and C08f8.8
    ortholog to Nr2e1, Rattus norvegicus
    ortholog to NR2E1, Pan troglodytes
    ortholog to nr2e1, Danio rerio
    Homologene
    FAMILY
  • nuclear receptor subfamily 2, group E
  • steroid nuclear receptor superfamily (see TSG6F)
  • nuclear hormone receptor family
    • CATEGORY transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • controles of neural cytoarchitectural organization
  • a highly conserved transcription factor known to be a key stem cell fate determinant in both the developing mouse forebrain and retina
  • crucial for the acquisition and maintenance of mature phenotypes of Müller cells and astrocytes
  • critical for the control of generating appropriate numbers of retinal astrocytes and is required for the expression of R-cadherin, and is a critical component of vasculogenesis, in astrocytes
  • an essential component of the molecular network involved in the hypoxia-inducible proangiogenic switch in retinal astrocytes
  • plays an important role in neural development by regulating cell cycle progression
  • upstream regulator of the PAX2 signaling cascade
  • playing a role in maintaining the undifferentiated, proliferative state of adult neural stem cells
  • regulates the expression of target genes by functioning as a constitutive transrepressor
  • transcription factor that is essential for neural stem cell proliferation and self-renewal (recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation)
  • inducer of SIRT1 and may contribute to neurogenesis both as a transactivator and as a repressor (Iwahara 2009)
  • represses gene expression by binding a consensus site, AAGTCA (the TLX-binding site), in the promoter region, and potentiates the retinoic acid-dependent transactivation of RARB2 (Iwahara 2009)
  • recruiting KDM1A to the promoters of NR2E1 target genes to repress their expression (sun 2010)
  • critical role for NR2E1 in Neural stem cells (NSCs)-dependent gliomagenesis
  • nuclear receptor crucial for neural stem cell proliferation and maintenance
  • in addition to having a role in preventing premature cell cycle exit, participates in several other developmental processes during retinogenesis including neurite organization in the inner retina and development of glycinergic amacrine cells, S-cones, and Müller glia
  • regulates processes involved in neurite development and terminal retinal cell differentiation
  • is vital for the expression of genes implicated in neurogenesis, such as DNA replication, cell cycle, adhesion and migration
  • has likely functions beyond regulation of adult hippocampal neurogenesis
  • plays an oncogenic role in prostate carcinogenesis by suppressing oncogene-induced senescence
  • acts likely through E2F6 to regulate beta cell proliferation
  • may act as a potential target to improve insulin sensitivity and inflammation in obesity and related complications
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text neurogenesis
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding to hormone response elements (HRE) containing an extended core motif half-site sequence 5'-AAGGTCA-3'
    RNA
    small molecule metal binding, other,
  • Zn2+
  • E2F6 is strongly downregulated by NR2E1, and its expression inhibits beta cell proliferation
  • oleic acid is critical for neural stem cell survival, and it binds to NR2E1 to convert it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes
    • protein
  • Atrophin
  • HDAC3 and HDAC5
  • histone demethylase LSD1
  • BCL11A is a novel NR2E1 coregulator that might be involved in NR2E1-dependent gene regulation in the brain
  • NR2E1 binds at the CBX7 promoter, inducing its expression
  • NR2E1 regulates CBX7 and restrains senescence in neural stem cells (NSCs)
  • NR2E1 could bind directly to AR promoter and repress AR transcription by recruitment of histone modifiers
  • E2F6 is strongly downregulated by NR2E1, and its expression inhibits beta cell proliferation
    • cell & other
    REGULATION
    Other Oleic acid thus serves as a metabolic regulator of NR2E1 activity
    NR2E1 could be regulated by RA, which would aid a better understanding of the mechanism underlying retinoic acid (RA)-induced brain abnormality
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       gain of function
    in prostate cancer
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerbrain 
    therapeutic target to inhibit the development of NSC-derived brain tumors
    cancerreproductiveprostate
    targeting the druggable NR2E1 may have a potential therapeutic significance in castration-resistant prostate cancer (CRPC) management
    ANIMAL & CELL MODELS
  • Mice lacking the Nr2e1 gene (Tlx&
    • 8722;/&
    8722;) are viable at birth but adults show a reduction in the size of rhinencephalic and limbic structures, including the olfactory, infrarhinal and entorhinal cortex, amygdala and dentate gyrus
  • Nr2e1-null mice have retinal and optic nerve dystrophy, leading to blindness
  • the extracellular assembly of fibronectin matrices by retinal astrocytes is severely impaired in mice null for Tlx, leading to defective scaffold formation and a complete failure of normal retinal vascular development
  • Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone
  • cerebrum and olfactory bulb hypoplasia, hallmarks of the Nr2e1-null phenotype, were not fully corrected in animals harboring one functional copy of human NR2E1 but retinal histology and electroretinograms are completely corrected
  • mice lacking Tlx (Nr2e1(-/-)) display deficits in adult hippocampal neurogenesis and behavioural abnormalities