Aliases for NR3C1 Gene
- Nuclear Receptor Subfamily 3 Group C Member 1 2 3 4 5
- Glucocorticoid Receptor 2 3 4
- GR 2 3 4
- Nuclear Receptor Subfamily 3, Group C, Member 1 (Glucocorticoid Receptor) 2 3
- GRL 3 4
- Nuclear Receptor Subfamily 3 Group C Member 1 Variant HGR-B(54) 3
- Nuclear Receptor Subfamily 3 Group C Member 1 Variant HGR-B(77) 3
External Ids for NR3C1 Gene
Previous HGNC Symbols for NR3C1 Gene
Previous GeneCards Identifiers for NR3C1 Gene
This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175). [provided by RefSeq, Feb 2011]
GeneCards Summary for NR3C1 Gene
NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1) is a Protein Coding gene. Diseases associated with NR3C1 include Glucocorticoid Resistance, Generalized and Post-Traumatic Stress Disorder. Among its related pathways are Signaling by GPCR and Signaling by PTK6. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and RNA polymerase II proximal promoter sequence-specific DNA binding. An important paralog of this gene is NR3C2.
UniProtKB/Swiss-Prot Summary for NR3C1 Gene
Receptor for glucocorticoids (GC) (PubMed:27120390). 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 (PubMed:9590696). 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 (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity).
[Isoform Alpha]: Has transcriptional activation and repression activity (PubMed:15866175, PubMed:19248771, PubMed:20484466, PubMed:23820903, PubMed:11435610, PubMed:15769988, PubMed:17635946, PubMed:19141540, PubMed:21664385). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression (By similarity).
[Isoform Beta]: Acts as a dominant negative inhibitor of isoform Alpha (PubMed:7769088, PubMed:8621628, PubMed:20484466). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253).
[Isoform Alpha-2]: Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466).
[Isoform GR-P]: Increases activity of isoform Alpha.
[Isoform Alpha-B]: More effective than isoform Alpha in transcriptional activation, but not repression activity.
[Isoform 10]: Has transcriptional activation activity.
[Isoform Alpha-C1]: Has transcriptional activation activity.
[Isoform Alpha-C2]: Has transcriptional activation activity.
[Isoform Alpha-C3]: Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903).
[Isoform Alpha-D1]: Has transcriptional activation activity.
[Isoform Alpha-D2]: Has transcriptional activation activity.
[Isoform Alpha-D3]: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127).
Glucocorticoid receptors (GRs) are nuclear hormone receptors of the NR3C class, which also includes mineralocorticoid, progesterone and androgen receptors. They exist as homodimers coupled to Hsp90 or HMGB proteins, which are shed upon activation.