GR a ligand-activated transcription factor of the nuclear receptor family. Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Belongs to the nuclear hormone receptor family. NR3 subfamily. Widely expressed including bone, stomach, lung, liver, colon, breast, ovary, pancreas and kidney. In the heart, detected in left and right atria, left and right ventricles, aorta, apex, intraventricular septum, and atrioventricular node as well as whole adult and fetal heart. 16 alternative splicing and alternative initiation human isoforms have been reported. Isoform 1 has transcriptional activation and repression activity. Mediates glucocorticoid-induced apoptosis. Promotes accurate chromosome segregation during mitosis. May act as a tumor suppressor. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression. Isoform 2 acts as a dominant negative inhibitor of isoform 1. Has intrinsic transcriptional activity independent of isoform 1 when both are coexpressed. Has no hormone-binding activity. May play a role in controlling glucose metabolism by maintaining insulin sensitivity. Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform 1-dependent manner. Directly regulates STAT1 expression in isoform 1-independent manner. Widely expressed including brain, bone marrow, thymus, spleen, liver, kidney, pancreas, lung, fat, skeletal muscle, heart, placenta and blood leukocytes. Isoform 3 has lower transcriptional activation activity than isoform 1. Exerts a dominant negative effect on isoform 1 via a trans-repression mechanism. Isoform 4 increases activity of isoform 1. Isoform 8 more effective than isoform 1 in transcriptional activation, but not repression activity. Isoform 13 has highest transcriptional activation activity of all isoforms created by alternative initiation. Has transcriptional repression activity. Mediates glucocorticoid-induced apoptosis. Isoform 16 has lowest transcriptional activation activity of all isoforms created by alternative initiation. Has transcriptional repression activity. Note: This description may include information from UniProtKB.
Protein type: DNA-binding; Mitochondrial; Nuclear receptor; Transcription factor
Chromosomal Location of rat Ortholog: 18p11
Cellular Component:  cytoplasm; cytosol; dendritic spine; glutamatergic synapse; membrane; microtubule organizing center; mitochondrion; neuron projection; nuclear speck; nucleoplasm; nucleus; postsynaptic density; postsynaptic density, intracellular component; protein-containing complex; spindle
Molecular Function:  chromatin binding; core promoter binding; DNA binding; DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription factor activity; double-stranded DNA binding; glucocorticoid receptor activity; heat shock protein binding; hormone binding; Hsp70 protein binding; Hsp90 protein binding; nuclear receptor activity; protein binding; protein dimerization activity; protein heterodimerization activity; protein homodimerization activity; protein kinase binding; protein-containing complex binding; receptor tyrosine kinase binding; RNA polymerase II proximal promoter sequence-specific DNA binding; RNA polymerase II regulatory region DNA binding; sequence-specific DNA binding; steroid binding; steroid hormone binding; SUMO binding; transcription coactivator activity; transcription factor binding; zinc ion binding
Biological Process:  adrenal gland development; aging; androgen metabolic process; brain development; cellular response to dexamethasone stimulus; cellular response to glucocorticoid stimulus; cellular response to magnesium ion; cellular response to steroid hormone stimulus; cellular response to transforming growth factor beta stimulus; chromatin remodeling; chromatin-mediated maintenance of transcription; circadian rhythm; female pregnancy; glucocorticoid mediated signaling pathway; glucocorticoid metabolic process; glucocorticoid receptor signaling pathway; lung development; mammary gland duct morphogenesis; maternal behavior; muscle atrophy; negative regulation of apoptotic process; negative regulation of glucocorticoid mediated signaling pathway; negative regulation of synaptic plasticity; negative regulation of transcription by RNA polymerase II; negative regulation of vascular permeability; positive regulation of cell growth involved in cardiac muscle cell development; positive regulation of dendritic spine development; positive regulation of glucocorticoid receptor signaling pathway; positive regulation of glutamate secretion; positive regulation of neuron apoptotic process; positive regulation of pri-miRNA transcription by RNA polymerase II; positive regulation of transcription by RNA polymerase II; regulation of cell proliferation; regulation of glucocorticoid biosynthetic process; regulation of gluconeogenesis; regulation of glucose metabolic process; regulation of transcription, DNA-templated; response to activity; response to arsenic-containing substance; response to calcium ion; response to corticosterone; response to dexamethasone; response to electrical stimulus; response to inactivity; response to insulin; response to mercury ion; response to radiation; transcription, DNA-templated
Reference #:  P06536 (UniProtKB)
Alt. Names/Synonyms: Gcr; Glucocorticoid receptor; GR; Grl; Nr3c1; Nuclear receptor subfamily 3 group C member 1; nuclear receptor subfamily 3, group C, member 1
Gene Symbols: Nr3c1
Molecular weight: 87,556 Da
Basal Isoelectric point: 6.38  Predict pI for various phosphorylation states
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  RCSB PDB  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene  |  NURSA