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Details on Person UniProt:P06537-2 Nr3c1
| Class:Id | ReferenceIsoform:147854 |
|---|---|
| _chainChangeLog | chain:1-783 added on Fri February 6 2015;chain:1-783 for 147854 removed on Fri February 25 2022;chain:1-792 for 147854 added on Fri February 25 2022 |
| _displayName | UniProt:P06537-2 Nr3c1 |
| _timestamp | 2025-02-21 19:28:04 |
| chain | chain:1-792 |
| checksum | 528730BD2C517554 |
| comment | 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 (PubMed:10678832). 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 (By similarity). 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 (PubMed:15037546).FUNCTION Has transcriptional activation and repression activity (By similarity). Mediates glucocorticoid-induced apoptosis (By similarity). 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 (PubMed:21994940).FUNCTION Acts as a dominant negative inhibitor of isoform 1 (PubMed:20660300). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (By similarity). Loses this transcription modulator function on its own (By similarity). Has no hormone-binding activity (PubMed:20660300). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (PubMed:20660300). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (By similarity). Directly regulates STAT1 expression in isoform Alpha-independent manner (By similarity).SUBUNIT Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:21994940, PubMed:9195923). 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 (PubMed:11278753, PubMed:9195923). 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 (By similarity). Directly interacts with UNC45A (By similarity). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers (PubMed:9528750). Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (PubMed:9742105). Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (By similarity). Interaction with BAG1 inhibits transactivation (By similarity). Interacts with HEXIM1 and TGFB1I1 (PubMed:10848625). Interacts with NCOA1 (By similarity). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (PubMed:22170608, PubMed:28751364). Interacts with CIART (PubMed:24736997). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with GRIP1 (By similarity). Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (By similarity). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (By similarity). Interacts with GSK3B (By similarity). Interacts with FNIP1 and FNIP2 (By similarity). Interacts (via C-terminus) with HNRNPU (via C-terminus) (By similarity). Interacts with MCM3AP (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (PubMed:27686098). In the absence of hormonal ligand, interacts with TACC1 (By similarity). Interacts (via NR LBD domain) with ZNF764 (via KRAB domain); the interaction regulates transcription factor activity of NR3C1 by directing its actions toward certain biologic pathways (By similarity).INTERACTION After ligand activation, translocates from the cytoplasm to the nucleus (PubMed:11278753). The hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment (PubMed:10678832). In the presence of NR1D1 shows a time-dependent subcellular localization, localizing to the cytoplasm at ZT8 and to the nucleus at ZT20 (PubMed:27686098). Lacks this diurnal pattern of localization in the absence of NR1D1, localizing to both nucleus and the cytoplasm at ZT8 and ZT20 (PubMed:27686098). Upon dexamethasone binding associates with the glucocorticoid response elements of target genes (PubMed:30698747).SUBCELLULAR LOCATION After ligand activation, translocates from the cytoplasm to the nucleus.SUBCELLULAR LOCATION Expressed predominantly in the nucleus with some expression also detected in the cytoplasm.ALTERNATIVE PRODUCTS Expressed in spleen, kidney and liver (PubMed:20660300). Expressed in a circadian manner in the liver (PubMed:27686098).TISSUE SPECIFICITY Expressed at highest level in spleen with lesser amounts in kidney and liver.INDUCTION Down-regulated by glucocorticoids.INDUCTION Up-regulated by glucocorticoids and insulin.DOMAIN 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.PTM Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity.PTM Increased proteasome-mediated degradation in response to glucocorticoids.PTM 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 (By similarity). Phosphorylation at Ser-229 increases transcriptional activity (By similarity). Phosphorylation at Ser-221, Ser-243 and Ser-421 decreases signaling capacity (By similarity). Phosphorylation at Ser-421 may protect from glucocorticoid-induced apoptosis (By similarity). Phosphorylation at Ser-221 and Ser-229 is not required in regulation of chromosome segregation (By similarity). May be dephosphorylated by PPP5C, attenuates NR3C1 action (PubMed:21994940).PTM 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.PTM Ubiquitinated (PubMed:11555652). Ubiquitination by UBR5 leads to its degradation: UBR5 specifically recognizes and binds ligand-bound NR3C1 when it is not associated with coactivators (NCOAs) (By similarity). In presence of NCOAs, the UBR5-degron is not accessible, preventing its ubiquitination and degradation (By similarity).POLYMORPHISM The poly-Gln region in 78-91 is polymorphic (PubMed:15489334, PubMed:16141072, PubMed:17012242, PubMed:20660300, PubMed:3780669). Polymorphism plays a role in complex mechanisms leading to lower corticosterone response to stress, and may also be associated with decreased locomotive and increased anxiety-type behaviors (PubMed:17012242).MISCELLANEOUS T-cell is a critical cellular target of GR, as immune activation in mice lacking GR resulted in significant mortality. This lethal activation is rescued by PTGS2 inhibition but not steroid administration or cytokine neutralization.MISCELLANEOUS Produced by alternative splicing.MISCELLANEOUS Produced by alternative initiation at Met-28 of isoform 1.MISCELLANEOUS Produced by alternative initiation at Met-28 of isoform 2.SIMILARITY Belongs to the nuclear hormone receptor family. NR3 subfamily. |
| description | recommendedName: Glucocorticoid receptor shortName: GR alternativeName: Nuclear receptor subfamily 3 group C member 1 |
| geneName | Nr3c1 Grl Grl1 |
| identifier | P06537 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative initiation Alternative splicing Chromatin regulator Chromosome Cytoplasm Cytoskeleton DNA-binding Isopeptide bond Lipid-binding Metal-binding Methylation Mitochondrion Nucleus Phosphoprotein Receptor Reference proteome Steroid-binding Transcription Transcription regulation Ubl conjugation Zinc Zinc-finger |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:3132113] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8934940] Weiser, JD [InstanceEdit:8944791] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9607352] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9688885] Weiser, JD [InstanceEdit:9750299] Weiser, JD [InstanceEdit:9767224] Weiser, Joel [InstanceEdit:9773244] Weiser, Joel [InstanceEdit:9834092] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | Nr3c1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | GCR_MOUSE E0ZPU5 E9PUR6 E9PYV1 Q06VW2 Q3U126 Q3U2M7 Q61628 Q61629 |
| sequenceLength | 792 |
| species | [Species:48892] Mus musculus |
| variantIdentifier | P06537-2 |
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No pathways have been reviewed or authored by UniProt:P06537-2 Nr3c1 (147854)
