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. 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. Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C. Upon ligand binding FKBP5 dissociates from the complex and FKBP4 takes its place, thereby linking the complex to dynein and mediating transport to the nucleus, where the complex dissociates. Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23. Directly interacts with UNC45A. Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers. Interacts with NRIP1, POU2F1, POU2F2 and TRIM28. Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6. Interaction with BAG1 inhibits transactivation. Interacts with HEXIM1 and TGFB1I1. Interacts with NCOA1. Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1. Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion. Interacts with CIART. Interacts with RWDD3. Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3. Interacts with GRIP1. Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation. Interacts with GSK3B. Interacts with FNIP1 and FNIP2. Interacts (via C-terminus) with HNRNPU (via C-terminus). Interacts with MCM3AP (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (By similarity). After ligand activation, translocates from the cytoplasm to the nucleus (By similarity). In the presence of NR1D1 shows a time-dependent subcellular localization, localizing to the cytoplasm at ZT8 and to the nucleus at ZT20 (By similarity). Lacks this diurnal pattern of localization in the absence of NR1D1, localizing to both nucleus and the cytoplasm at ZT8 and ZT20 (By similarity). Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required. 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 glucocorticoid. The Ser-208, Ser-231 and Ser-410-phosphorylated forms are mainly cytoplasmic, and the Ser-216-phosphorylated form is nuclear. Phosphorylation at Ser-216 increases transcriptional activity. Phosphorylation at Ser-208, Ser-231 and Ser-410 decreases signaling capacity. Phosphorylation at Ser-410 may protect from glucocorticoid-induced apoptosis. Phosphorylation at Ser-208 and Ser-216 is not required in regulation of chromosome segregation. May be dephosphorylated by PPP5C, attenuates NR3C1 action. Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling. Sumoylation at Lys-282 and Lys-298 negatively regulates its transcriptional activity. Sumoylation at Lys-708 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-282 and Lys-298 is dispensable whereas sumoylation at Lys-708 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWDD3-dependent manner. Belongs to the nuclear hormone receptor family. NR3 subfamily.