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FLASH GENE
Symbol NR3C1 contributors: mct/npt - updated : 10-05-2016
HGNC name nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)
HGNC id 7978
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • receptor composed of a N terminal modulator domain
  • a hinge region homologous only with those of the oxosteroid receptors
  • a central bipartite zinc finger DNA binding domain followed by a nuclear localization signal (NLS)
  • activation function 1 (AF1) in the N-terminal half of NR3C1
  • C terminal ligand binding domain including a transactivation and dimerization domain (important in conferring transactivational activity), the AF2 domain in the C-terminal ligand-binding domain (LBD)
    • HOMOLOGY
    interspecies homolog to rattus Nr3c1 (90.83 pc)
    homolog to murine Nr3c1 (90.44 pc)
    Homologene
    FAMILY
  • nuclear hormone receptor family
  • NR3 subfamily
    • CATEGORY transcription factor , signaling hormone , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • nuclear hormone receptor that regulates multiple physiological and pathophysiological processes (Niu 2009)
  • inhibit erythroid maturation not only through a transcriptional mechanism, but also through a rapid membrane-associated pathway that interferes with EPO receptor signaling (Stellacci 2009)
  • regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes (Meijsing 2009)
  • coactivation of NR3C1 and NFKB alters signaling pathways that are regulated by each factor separately and provide insight into the networks underlying the NR3C1 and NFKB crosstalk
  • endothelial NR3C1 is a critical regulator of NFKB1 activation and nitric oxide synthesis in sepsis
  • in the brain, has been implicated, amongst others, in feedback regulation of the hypothalamic-pituitary-adrenal axis, with potential deficits during aging and in depression
  • is required for fetal heart maturation
  • ligand-dependent transcription factor of the nuclear receptor superfamily
  • NR3C1 -dependent repression of elongation-controlled genes was abolished specifically in negative elongation factor-deficient macrophages
  • both NR3C1 and FOXO1 are required for ANGPTL4 transcription activation, and FOXO1 negatively mediates the suppressive effect of insulin
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with tissue-specific transcriptional activators required for receptor actin (see HNFS)
  • upregulating HIF1 gene expression under hypoxic conditions
  • transcriptional activity suppressed with association yoGbetagamma complexes
  • PMF1 binds to the glucocorticoid receptor (NR3C1), and represses glucocorticoid-induced transcription
  • ANGPTL4 is a direct target that participates in glucocorticoid-regulated triglyceride metabolism (Koliwad 2009)
  • interacting with SKA2 in cancer cells (Rice 2008)
  • NUP62 and NR3C1 were able to interact in a more efficient manner when chaperoned by the HSP90-based heterocomplex
  • role for GPR50 in NR3C1 signalling through interaction with kat5
  • FOXA1 is a potent enhancer of NR3C1-induced transcription
  • molecular interplay of NR3C1 and MEF2A in the control of genes important for neuronal plasticity
  • GSK3B is important for NR3C1 transactivation activity and GSK3B inhibition suppresses NR3C1-stimulated gene expression
  • FOXO3 is an immediate early glucocorticoid receptor (NR3C1) target, whose transcription is even further enhanced by conditions that mimic metabolic stress
  • AGRP is a common orexigenic target gene of NR3C1 and BSX
  • mutual antagonism between NR4A3 and NR3C1 to be a key rheostat for peripheral metabolic signals to centrally control energy balance
  • NR3C1-induced expression of HNF4A may likely contribute to indirect SLC22A1 gene up-regulation by dexamethasone in primary human hepatocytes, but not in hepatocyte-derived tumor cell lines
  • BUD23 is a novel regulator of chromatin structure affecting NR3C1 recruitment and function, contributing to loss of NR3C1 sensitivity in inflammation, with suppressed expression in pulmonary disease
  • NR1D1 influences the stability and nuclear localization of NR3C1
  • MDFIC is a binding partner for NR3C1, and NR3C1 directly represses the MDFIC gene, revealing a negative feedback loop by which glucocorticoids limit MDFIC activity
    • cell & other
    REGULATION
    activated by ligand-induced activity of N3C1 is enhanced by DAP3
    Other phosphorylated by activated JNK (phosphorylates NR3C1 at Ser226, enhances its nuclear export after withdrawal of a ligand for NR3C1, dexamethasone, and may contribute to termination of NR3C1-mediated transcription) (Itoh 2002)
    GSK3B regulates NR3C1 response by genomic and nongenomic mechanisms
    ASSOCIATED DISORDERS
    corresponding disease(s) GRL
    related resource Glucocorticoid Receptor Resource database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral        
    NR3C1 gene inactivated through promoter hypermethylation in colorectal tumor development
    Susceptibility
    Variant & Polymorphism
    Candidate gene DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC (Kang 2008)
    Marker
    Therapy target
    ANIMAL & CELL MODELS