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FLASH GENE
Symbol NR1D1 contributors: mct - updated : 17-02-2017
HGNC name nuclear receptor subfamily 1, group D, member 1
HGNC id 7962
DNA
TYPE functioning gene
SPECIAL FEATURE overlapping, gene in gene, opposite orientation, antisens
text partially overlapping THRA (exon for THRA2) on the opposite strand
STRUCTURE 7.94 kb     8 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
8 - 2788 66.8 614 - 2008 17996965
EXPRESSION
Rna function photoreceptor
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousnerve   highly
Respiratoryrespiratory tractlarynx  highly
Visualeye   highly
cell lineage
cell lines high level in some squamous carcinoma cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
mono polymer homomer , dimer
HOMOLOGY
interspecies homolog to C.elegans c01m6.5
Homologene
FAMILY
  • nuclear hormone receptor family
  • NR1 subfamily
  • steroid hormone receptor superfamily of ligand-activated transcription factors
  • CATEGORY regulatory , transcription factor , receptor nuclear
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • steroid hormone receptor
  • transcriptional repressor
  • orphan nuclear receptors that function as dominant transcriptional silencer
  • potent transcriptional repressor that regulates circadian rhythm and metabolism
  • being necessary for the early mitotic events that are required for adipogenesis
  • participates in the circadian modulation of sterol regulatory element-binding protein (SREBF) activity, and thereby in the daily expression of SREBF target genes involved in cholesterol and lipid metabolism
  • repression of gene transcription by NR1D1 plays an integral role in the core molecular circadian clock
  • RORA and NR1D1 coordinately regulate the expression of the positive arm of the circadian rhythm feedback loop
  • transcriptional repressor that is expressed in a circadian manner and the abundance of NR1D1 protein oscillated in phase with HDAC3 recruitment
  • colocalizes with HDAC3 near genes regulating lipid metabolism
  • genomic recruitment of HDAC3 by NR1D1 directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis
  • a potential role for NR1D1, in conjunction with its cofactor NR2E3, in regulating transcriptional networks critical for photoreceptor development and function (
  • plays a dual role in regulation of the activity of the ARNTL/CLOCK heterodimer by regulation of expression of both the ARNTLand CLOCK genes
  • mediates circadian regulation of innate immunity through selective regulation of inflammatory cytokines
  • NR1D1, NR1D2 are major regulators of both clock function and metabolism, displaying a level of subtype collaboration that is unusual among nuclear receptors but common among core clock proteins
  • controls circadian oscillations of several clock genes and its degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation
  • is a pharmacological target that improves muscle oxidative function by modulating gene networks controlling mitochondrial number and function
  • may be a key link between aging- or obesity-associated impairment of clockwork and inflammation
  • NR1D1 and NR4A1 serve similar or complementary functions in the APOA4-mediated regulation of gluconeogenesis
  • NR1D1 and NR1D2 are transcription factors that play pivotal roles in the regulation of the circadian rhythm and various metabolic processes
  • plays a major role in retinal information processing
  • nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • NR1D1 is a new intracellular regulator of glucagon secretion via AMPK/NAMPT/SIRT1 pathway
  • a component
    INTERACTION
    DNA binding to specific sequence Rev-erb alpha responsive element (Rev-RE)
    RNA
    small molecule
    protein
  • interacting with NR2E3 (activating the promoters of rod phototransduction genes)
  • heme receptor
  • recruits HTATIP and HDAC1 to regulate apolipoprotein CIII promoter
  • could also mediate repression via ID1 binding in the absence of heme
  • regulates the expression of NPAS2, a heterodimer partner of ARNTL, and also regulates the expression another heterodimer partner of ARNTL, CLOCK
  • CCAR2 is a novel regulator of NR1D1 and modulates the NR1D1 repressor function
  • NR1D1 regulates the inflammatory infiltration of macrophages through the suppression of CCL2 expression
  • APOA4 reduces hepatic gluconeogenesis through nuclear receptor NR1D1
  • FABP7 is a direct target of repression by NR1D1
  • expression of CACNA1C mRNA was rhythmic (peaking during the late night) and regulated by the circadian clock component NR1D1
  • SIAH2 is a previously unidentified circadian clockwork regulator that mediates circadian NR1D1 turnover
  • NR1D1, is a cofactor in APOA4-mediated downregulation of gluconeogenesis, and APOA4-induced increase in NR4A1 expression in hepatocytes mediates further repression of gluconeogenesis
  • is a specific modulator of FGF21 signaling in adipose tissue
  • core inhibitory component of clock transcription, targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7
  • NR1D1 influences the stability and nuclear localization of NR3C1
  • NR1D1 is a direct target of STRA8 transcriptional repression
  • SPSB4 is a putative novel E3 ligase for NR1D1 (
  • cell & other
    REGULATION
    Other regulated by RORA at the transcriptional level
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    may represent a unique therapeutic target in human inflammatory disease
    ANIMAL & CELL MODELS
    deletion of Hdac3 or Nr1d1 in mouse liver causes hepatic steatosis