| Tissue Specificity | Expressed in spleen, kidney and liver. Expressed in a circadian manner in the liver. Isoform 3: Expressed at highest level in spleen with lesser amounts in kidney and liver. |
| Post Translational Modifications | Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity. Increased proteasome-mediated degradation in response to glucocorticoids. Phosphorylated in the absence of hormone.becomes hyperphosphorylated in the presence of glucocorticoids. Phosphorylated in the absence of hormone.becomes hyperphosphorylated in the presence of glucocorticoid. The Ser-221, Ser-243 and Ser-421-phosphorylated forms are mainly cytoplasmic, and the Ser-229-phosphorylated form is nuclear. Phosphorylation at Ser-229 increases transcriptional activity. Phosphorylation at Ser-221, Ser-243 and Ser-421 decreases signaling capacity. Phosphorylation at Ser-421 may protect from glucocorticoid-induced apoptosis. Phosphorylation at Ser-221 and Ser-229 is not required in regulation of chromosome segregation. May be dephosphorylated by PPP5C, attenuates NR3C1 action. Sumoylation at Lys-294 and Lys-310 negatively regulates its transcriptional activity. Sumoylation at Lys-718 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-294 and Lys-310 is dispensable whereas sumoylation at Lys-718 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWDD3-dependent manner. Ubiquitinated. Ubiquitination by UBR5 leads to its degradation: UBR5 specifically recognizes and binds ligand-bound NR3C1 when it is not associated with coactivators (NCOAs). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation. |
| Function | 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. 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. 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 3: Acts as a dominant negative inhibitor of isoform 1. Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed. Loses this transcription modulator function on its own. 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 Alpha-dependent manner. Directly regulates STAT1 expression in isoform Alpha-independent manner. |
| Protein Name | Glucocorticoid ReceptorGrNuclear Receptor Subfamily 3 Group C Member 1 |
| Database Links | Reactome: R-MMU-3371497Reactome: -MMU-383280Reactome: -MMU-4090294 |
| Cellular Localisation | CytoplasmNucleusMitochondrionCytoskeletonSpindleMicrotubule Organizing CenterCentrosomeChromosomeNucleoplasmAfter Ligand ActivationTranslocates From The Cytoplasm To The NucleusThe Hormone-Occupied Receptor Undergoes Rapid Exchange Between Chromatin And The Nucleoplasmic CompartmentIn The Presence Of Nr1d1 Shows A Time-Dependent Subcellular LocalizationLocalizing To The Cytoplasm At Zt8 And To The Nucleus At Zt20Lacks This Diurnal Pattern Of Localization In The Absence Of Nr1d1Localizing To Both Nucleus And The Cytoplasm At Zt8 And Zt20Upon Dexamethasone Binding Associates With The Glucocorticoid Response Elements Of Target GenesIsoform 1: CytoplasmIsoform 3: NucleusExpressed Predominantly In The Nucleus With Some Expression Also Detected In The Cytoplasm |
| Alternative Antibody Names | Anti-Glucocorticoid Receptor antibodyAnti-Gr antibodyAnti-Nuclear Receptor Subfamily 3 Group C Member 1 antibodyAnti-Nr3c1 antibodyAnti-Grl antibodyAnti-Grl1 antibody |
Information sourced from Uniprot.org
