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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
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