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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

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 Nervous brain       specific Drosophila melanogaster Fetal   brain forebrain       Mus musculus Adult   brain limbic system hippocampus dentate gyrus   Mus musculus Visual eye retina     highly Mus musculus Adult

cells

System Cell Pubmed Species Stage Rna symbol Visual Muller cell Mus musculus Adult NM_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)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function in prostate cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer brain   therapeutic target to inhibit the development of NSC-derived brain tumors cancer reproductive prostate 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