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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
DNA
TYPE functioning gene
SPECIAL FEATURE head to head
STRUCTURE 22.80 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter
Binding site
text structure a consensus site, AAGTCA (the TLX-binding site), in the promoter region (Iwahara 2009)
MAPPING cloned Y linked N status provisional
Map cen - D6S268 - D6S1635 - NR2E1 - D6S1594 - D6S2431 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 3271 42 385 - 2021 34463725
9 - 2631 - 422 - 2021 34463725
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   specific Drosophila melanogasterFetal
 brainforebrain    Mus musculusAdult
 brainlimbic systemhippocampusdentate gyrus  Mus musculus
Visualeyeretina  highly Mus musculusAdult
cells
SystemCellPubmedSpeciesStageRna symbol
VisualMuller cell Mus musculusAdultNM_152229
cell lineage
  • expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation
  • specific expression in periventricular neural stem cells in embryonic brains
  • cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text developing fore/midbrain neuroepithelium
    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