UniProtKB - P04150 (GCR_HUMAN)
Protein
Glucocorticoid receptor
Gene
NR3C1
Organism
Homo sapiens (Human)
Status
Functioni
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).By similarity3 Publications
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).By similarity11 Publications
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).By similarity5 Publications
Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466).
Increases activity of isoform Alpha.1 Publication
More effective than isoform Alpha in transcriptional activation, but not repression activity.2 Publications
Has transcriptional activation activity.1 Publication
Has transcriptional activation activity.1 Publication
Has transcriptional activation activity.1 Publication
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).3 Publications
Has transcriptional activation activity.1 Publication
Has transcriptional activation activity.1 Publication
Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127).3 Publications
Miscellaneous
Can up- or down-modulate aggregation and nuclear localization of expanded polyglutamine polypeptides derived from AR and HD through specific regulation of gene expression. Aggregation and nuclear localization of expanded polyglutamine proteins are regulated cellular processes that can be modulated by this receptor, a well-characterized transcriptional regulator.1 Publication
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| DNA bindingi | 418 – 493 | Nuclear receptorPROSITE-ProRule annotationAdd BLAST | 76 | |
| Zinc fingeri | 421 – 441 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
| Zinc fingeri | 457 – 476 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 20 |
GO - Molecular functioni
- core promoter sequence-specific DNA binding Source: CAFA
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: NTNU_SB
- glucocorticoid receptor activity Source: ProtInc
- Hsp90 protein binding Source: UniProtKB
- nuclear receptor activity Source: UniProtKB
- protein kinase binding Source: ARUK-UCL
- repressing transcription factor binding Source: GO_Central
- RNA binding Source: UniProtKB-KW
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: NTNU_SB
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- steroid binding Source: UniProtKB
- steroid hormone binding Source: UniProtKB
- zinc ion binding Source: InterPro
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- cell cycle Source: UniProtKB-KW
- cell division Source: UniProtKB-KW
- cellular response to dexamethasone stimulus Source: CAFA
- cellular response to glucocorticoid stimulus Source: UniProtKB
- cellular response to steroid hormone stimulus Source: UniProtKB
- cellular response to transforming growth factor beta stimulus Source: CAFA
- chromatin organization Source: UniProtKB-KW
- chromosome segregation Source: UniProtKB-KW
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: NTNU_SB
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: ARUK-UCL
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
- signal transduction Source: ProtInc
- transcription initiation from RNA polymerase II promoter Source: Reactome
Keywordsi
| Molecular function | Chromatin regulator, DNA-binding, Receptor, RNA-binding |
| Biological process | Apoptosis, Cell cycle, Cell division, Chromosome partition, Mitosis, Transcription, Transcription regulation |
| Ligand | Lipid-binding, Metal-binding, Steroid-binding, Zinc |
Enzyme and pathway databases
| PathwayCommonsi | P04150 |
| Reactomei | R-HSA-3371497, HSP90 chaperone cycle for steroid hormone receptors (SHR) R-HSA-383280, Nuclear Receptor transcription pathway R-HSA-400253, Circadian Clock R-HSA-4090294, SUMOylation of intracellular receptors R-HSA-8849473, PTK6 Expression R-HSA-8939902, Regulation of RUNX2 expression and activity R-HSA-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes R-HSA-9679191, Potential therapeutics for SARS |
| SignaLinki | P04150 |
| SIGNORi | P04150 |
Names & Taxonomyi
| Protein namesi | Recommended name: Glucocorticoid receptorShort name: GR Alternative name(s): Nuclear receptor subfamily 3 group C member 1 |
| Gene namesi | Name:NR3C1 Synonyms:GRL |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| EuPathDBi | HostDB:ENSG00000113580.14 |
| HGNCi | HGNC:7978, NR3C1 |
| MIMi | 138040, gene |
| neXtProti | NX_P04150 |
Subcellular locationi
Cytoskeleton
- spindle 1 Publication
- centrosome 1 Publication
Nucleus
- Nucleus 5 Publications
Mitochondrion
- Mitochondrion 1 Publication
Other locations
- Cytoplasm 5 Publications
Note: After ligand activation, translocates from the cytoplasm to the nucleus. 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).By similarity3 Publications
Cytoskeleton
- microtubule organizing center Source: UniProtKB-SubCell
- spindle Source: UniProtKB-SubCell
Cytosol
- cytosol Source: HPA
Mitochondrion
- mitochondrial matrix Source: ProtInc
Nucleus
- nuclear chromatin Source: NTNU_SB
- nuclear speck Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, Mitochondrion, NucleusPathology & Biotechi
Involvement in diseasei
Glucocorticoid resistance, generalized (GCCR)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of Cushing syndrome typical signs. Clinical features include hypoglycemia, hypertension, metabolic alkalosis, chronic fatigue and profound anxiety.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_075799 | 423 | V → A in GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_013472 | 477 | R → H in GCCR. 1 PublicationCorresponds to variant dbSNP:rs104893913EnsemblClinVar. | 1 | |
| Natural variantiVAR_077143 | 477 | R → S in GCCR; loss of DNA-binding and of transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type. 1 Publication | 1 | |
| Natural variantiVAR_077144 | 478 | Y → C in GCCR; decreased DNA-binding and transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type. 1 Publication | 1 | |
| Natural variantiVAR_075800 | 556 | T → I in GCCR; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. 2 Publications | 1 | |
| Natural variantiVAR_015632 | 559 | I → N in GCCR; interferes with translocation to the nucleus and thereby strongly reduces transcription activation; is equally impaired in nuclear export; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs104893909EnsemblClinVar. | 1 | |
| Natural variantiVAR_075801 | 575 | V → G in GCCR; unknown pathological significance; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_004676 | 641 | D → V in GCCR. 1 PublicationCorresponds to variant dbSNP:rs104893908EnsemblClinVar. | 1 | |
| Natural variantiVAR_077145 | 672 | L → P in GCCR; loss of dexamethasone-binding, dexamethasone-induced translocation to the nucleus and of transactivation activity. 1 Publication | 1 | |
| Natural variantiVAR_013473 | 679 | G → S in GCCR; has 50% binding affinity. 1 PublicationCorresponds to variant dbSNP:rs104893914EnsemblClinVar. | 1 | |
| Natural variantiVAR_075802 | 714 | R → Q in GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_075803 | 726 | H → R in GCCR; unknown pathological significance; reduces transactivation and transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not impair DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_004677 | 729 | V → I in GCCR. 1 PublicationCorresponds to variant dbSNP:rs1027058734Ensembl. | 1 | |
| Natural variantiVAR_071935 | 737 | F → L in GCCR; reduces transactivation of the glucocorticoid-inducible tumor virus promoter; reduces affinity for ligand; delays its nuclear translocation; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs121909727EnsemblClinVar. | 1 | |
| Natural variantiVAR_015633 | 747 | I → M in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs104893910EnsemblClinVar. | 1 | |
| Natural variantiVAR_071936 | 773 | L → P in GCCR; reduces transactivation of the glucocorticoid-inducible tumor virus promoter; reduces affinity for ligand; delays its nuclear translocation; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs104893912EnsemblClinVar. | 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 1 | M → T: Abolishes expression of A-type isoforms. 2 Publications | 1 | |
| Mutagenesisi | 27 | M → T: Abolishes expression of B-type isoforms. 2 Publications | 1 | |
| Mutagenesisi | 86 | M → I: Abolishes expression of C-type isoforms; when associated with I-90 and I-98. 1 Publication | 1 | |
| Mutagenesisi | 90 | M → I: Abolishes expression of C-type isoforms; when associated with I-86 and I-98. 1 Publication | 1 | |
| Mutagenesisi | 98 | M → I: Abolishes expression of C-type isoforms; when associated with I-86 and I-90. 1 Publication | 1 | |
| Mutagenesisi | 101 | D → A: Reduces transcription activation activity of isoform Alpha-C3 by half. 1 Publication | 1 | |
| Mutagenesisi | 101 | D → K: Reduces transcription activation activity of isoform Alpha-C3 by half. Suppresses apoptosis-inducing activity of isoform Alpha-C3. Impairs recruitment of selected coregulators onto DNA binding sites. 1 Publication | 1 | |
| Mutagenesisi | 106 – 107 | QQ → LL: Reduces activity of isoform Alpha-C3 by half. 1 Publication | 2 | |
| Mutagenesisi | 113 – 114 | SS → AA: Does not affect the activity of isoform Alpha-C3. 1 Publication | 2 | |
| Mutagenesisi | 191 | F → D: Reduces transactivation by the ADA complex. 1 Publication | 1 | |
| Mutagenesisi | 193 | I → D: Reduces transactivation by the ADA complex. 1 Publication | 1 | |
| Mutagenesisi | 194 | L → A: Strongly reduces transactivation by the ADA complex; when associated with V-224 and F-225. 1 Publication | 1 | |
| Mutagenesisi | 197 | L → E: Reduces transactivation by the ADA complex. 1 Publication | 1 | |
| Mutagenesisi | 211 | S → A: Reduces expression of target genes IGFBP1 and IRF8. 1 Publication | 1 | |
| Mutagenesisi | 213 | W → A: Strongly reduces transactivation by the ADA complex. 1 Publication | 1 | |
| Mutagenesisi | 224 | L → V: Strongly reduces transactivation by the ADA complex; when associated with A-194 and F-225. 1 Publication | 1 | |
| Mutagenesisi | 225 | L → F: Strongly reduces transactivation by the ADA complex; when associated with A-194 and V-224. 1 Publication | 1 | |
| Mutagenesisi | 226 | S → A: Abolishes phosphorylation and enhances transcriptional activation. 1 Publication | 1 | |
| Mutagenesisi | 235 | F → L: Strongly reduces transactivation by the ADA complex; when associated with V-236. 1 Publication | 1 | |
| Mutagenesisi | 236 | L → V: Strongly reduces transactivation by the ADA complex; when associated with L-235. 1 Publication | 1 | |
| Mutagenesisi | 277 | K → R: Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-293. 1 Publication | 1 | |
| Mutagenesisi | 293 | K → R: Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-277. 1 Publication | 1 | |
| Mutagenesisi | 316 | M → I: Abolishes expression of D-type isoforms; when associated with I-331 and I-336. 1 Publication | 1 | |
| Mutagenesisi | 331 | M → I: Abolishes expression of D-type isoforms; when associated with I-316 and I-336. 1 Publication | 1 | |
| Mutagenesisi | 336 | M → I: Abolishes expression of D-type isoforms; when associated with I-316 and I-331. 1 Publication | 1 | |
| Mutagenesisi | 404 | S → A: Abolishes phosphorylation. Does not affect translocation to the nucleus following ligand stimulation. Increases protein half-life and transcriptional repressor activity. Alters repertoire of regulated genes. Increases cell death. 1 Publication | 1 | |
| Mutagenesisi | 404 | S → D: Does not affect translocation to the nucleus following ligand stimulation. 1 Publication | 1 | |
| Mutagenesisi | 480 | K → A: Decrease in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-492; A-494 and A-495. 1 Publication | 1 | |
| Mutagenesisi | 492 | K → A: Decrease in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-480; A-494 and A-495. 1 Publication | 1 | |
| Mutagenesisi | 494 | K → A: Decrease in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-495. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-480; A-492 and A-495. 1 Publication | 1 | |
| Mutagenesisi | 495 | K → A: Decrease in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-494. Complete loss in acetylation and in repression of its transcriptional activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated with A-480; A-492 and A-494. 1 Publication | 1 | |
| Mutagenesisi | 585 | R → A: Reduces activation mediated by ligand binding domain; when associated with A-590. 1 Publication | 1 | |
| Mutagenesisi | 590 | D → A: Reduces activation mediated by ligand binding domain; when associated with A-585. 1 Publication | 1 | |
| Mutagenesisi | 602 | F → S: Increases solubility. No effect on transactivation by dexamethasone. 1 Publication | 1 | |
| Mutagenesisi | 625 | P → A: Decreases transactivation by dexamethasone by 95%. 1 Publication | 1 | |
| Mutagenesisi | 628 | I → A: Decreases dimerization and transactivation by dexamethasone; when associated with S-602. 1 Publication | 1 | |
| Mutagenesisi | 703 | K → R: Slightly reduces sumoylation. Inhibits the stimulatory effect of RWDD3 on its transcriptional activity. 2 Publications | 1 |
Keywords - Diseasei
Disease mutation, PseudohermaphroditismOrganism-specific databases
| DisGeNETi | 2908 |
| MalaCardsi | NR3C1 |
| MIMi | 615962, phenotype |
| OpenTargetsi | ENSG00000113580 |
| Orphaneti | 786, Generalized glucocorticoid resistance syndrome |
| PharmGKBi | PA181 |
Miscellaneous databases
| Pharosi | P04150, Tclin |
Chemistry databases
| ChEMBLi | CHEMBL2034 |
| DrugBanki | DB00240, Alclometasone DB04630, Aldosterone DB00288, Amcinonide DB00394, Beclomethasone dipropionate DB00443, Betamethasone DB01222, Budesonide DB01410, Ciclesonide DB01013, Clobetasol propionate DB13158, Clobetasone DB00838, Clocortolone DB01380, Cortisone acetate DB13003, Cortivazol DB11921, Deflazacort DB01260, Desonide DB00547, Desoximetasone DB01234, Dexamethasone DB00223, Diflorasone DB09095, Difluocortolone DB06781, Difluprednate DB01395, Drospirenone DB00687, Fludrocortisone DB00663, Flumethasone DB00180, Flunisolide DB00591, Fluocinolone acetonide DB01047, Fluocinonide DB00324, Fluorometholone DB01185, Fluoxymesterone DB00846, Flurandrenolide DB13867, Fluticasone DB08906, Fluticasone furoate DB00588, Fluticasone propionate DB11619, Gestrinone DB02210, Hexane-1,6-Diol DB00769, Hydrocortamate DB00741, Hydrocortisone DB14538, Hydrocortisone aceponate DB14539, Hydrocortisone acetate DB14540, Hydrocortisone butyrate DB14541, Hydrocortisone cypionate DB14542, Hydrocortisone phosphate DB14543, Hydrocortisone probutate DB14544, Hydrocortisone valerate DB00367, Levonorgestrel DB14596, Loteprednol etabonate DB00253, Medrysone DB00351, Megestrol acetate DB00959, Methylprednisolone DB00834, Mifepristone DB00764, Mometasone DB14512, Mometasone furoate DB00717, Norethisterone DB12637, Onapristone DB05423, ORG-34517 DB01384, Paramethasone DB01130, Prednicarbate DB00860, Prednisolone DB15566, Prednisolone acetate DB14631, Prednisolone phosphate DB00635, Prednisone DB00396, Progesterone DB00896, Rimexolone DB14583, Segesterone acetate DB00421, Spironolactone DB09091, Tixocortol DB00620, Triamcinolone DB08867, Ulipristal DB00596, Ulobetasol |
| DrugCentrali | P04150 |
| GuidetoPHARMACOLOGYi | 625 |
Polymorphism and mutation databases
| BioMutai | NR3C1 |
| DMDMi | 121069 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000019937 | 1 – 777 | Glucocorticoid receptorAdd BLAST | 777 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length | |
|---|---|---|---|---|---|
| Modified residuei | 8 | PhosphothreonineCombined sources | 1 | ||
| Modified residuei | 23 | Omega-N-methylarginineBy similarity | 1 | ||
| Modified residuei | 45 | PhosphoserineCombined sources | 1 | ||
| Modified residuei | 113 | PhosphoserineBy similarity | 1 | ||
| Modified residuei | 134 | PhosphoserineCombined sources | 1 | ||
| Modified residuei | 141 | PhosphoserineBy similarity | 1 | ||
| Modified residuei | 203 | PhosphoserineCombined sources3 Publications | 1 | ||
| Modified residuei | 211 | Phosphoserine3 Publications | 1 | ||
| Modified residuei | 226 | PhosphoserineCombined sources1 Publication | 1 | ||
| Cross-linki | 258 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources | |||
| Modified residuei | 267 | PhosphoserineCombined sources | 1 | ||
| Cross-linki | 277 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication | |||
| Cross-linki | 277 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources | |||
| Cross-linki | 293 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication | |||
| Cross-linki | 293 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources | |||
| Modified residuei | 404 | Phosphoserine; by GSK3-beta1 Publication | 1 | ||
| Cross-linki | 419 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | |||
| Modified residuei | 480 | N6-acetyllysine1 Publication | 1 | ||
| Modified residuei | 492 | N6-acetyllysine1 Publication | 1 | ||
| Modified residuei | 494 | N6-acetyllysine1 Publication | 1 | ||
| Modified residuei | 495 | N6-acetyllysine1 Publication | 1 | ||
| Cross-linki | 703 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication | |||
| Isoform Alpha-B (identifier: P04150-8) | |||||
| Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | ||
| Isoform Beta-B (identifier: P04150-9) | |||||
| Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | ||
Post-translational modificationi
Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity.2 Publications
Increased proteasome-mediated degradation in response to glucocorticoids (PubMed:11555652). Isoform Alpha-B appears to be more susceptible to proteolytic degradation than isoform Alpha (PubMed:11435610).2 Publications
Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoid. The Ser-203, Ser-226 and Ser-404-phosphorylated forms are mainly cytoplasmic, and the Ser-211-phosphorylated form is nuclear (PubMed:12000743, PubMed:18838540). Phosphorylation at Ser-211 increases transcriptional activity (PubMed:12000743, PubMed:18483179). Phosphorylation at Ser-203, Ser-226 and Ser-404 decreases signaling capacity (PubMed:12000743, PubMed:18483179, PubMed:18838540). Phosphorylation at Ser-404 may protect from glucocorticoid-induced apoptosis (PubMed:18838540). Phosphorylation at Ser-203 and Ser-211 is not required in regulation of chromosome segregation (PubMed:25847991). May be dephosphorylated by PPP5C, attenuates NR3C1 action (By similarity).By similarity4 Publications
Sumoylation at Lys-277 and Lys-293 negatively regulates its transcriptional activity (PubMed:12144530). Sumoylation at Lys-703 positively regulates its transcriptional activity in the presence of RWDD3 (By similarity). Sumoylation at Lys-277 and Lys-293 is dispensable whereas sumoylation at Lys-703 is critical for the stimulatory effect of RWDD3 on its transcriptional activity (By similarity). Heat shock increases sumoylation in a RWDD3-dependent manner (By similarity).By similarity1 Publication
Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling.By similarity
Keywords - PTMi
Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
| EPDi | P04150 |
| jPOSTi | P04150 |
| MassIVEi | P04150 |
| PaxDbi | P04150 |
| PeptideAtlasi | P04150 |
| PRIDEi | P04150 |
| ProteomicsDBi | 51657 [P04150-1] 51658 [P04150-10] 51659 [P04150-2] 51660 [P04150-3] 51661 [P04150-5] 51662 [P04150-6] 51663 [P04150-7] 51664 [P04150-8] 51665 [P04150-9] |
PTM databases
| GlyGeni | P04150, 3 sites, 1 O-linked glycan (3 sites) |
| iPTMneti | P04150 |
| PhosphoSitePlusi | P04150 |
Expressioni
Tissue specificityi
Widely expressed including bone, stomach, lung, liver, colon, breast, ovary, pancreas and kidney (PubMed:25847991). 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 (PubMed:10902803). Isoform Beta: Widely expressed including brain, bone marrow, thymus, spleen, liver, kidney, pancreas, lung, fat, skeletal muscle, heart, placenta and blood leukocytes (PubMed:7769088, PubMed:8621628). Isoform Alpha-2: Expressed at low level.4 Publications
Inductioni
Isoform Alpha: Up-regulated by TNF (at protein level). Isoform Beta: Up-regulated by TNF and becomes the predominant isoform which may lead to glucocorticoid resistance (at protein level).1 Publication
Gene expression databases
| Bgeei | ENSG00000113580, Expressed in endothelial cell and 260 other tissues |
| ExpressionAtlasi | P04150, baseline and differential |
| Genevisiblei | P04150, HS |
Organism-specific databases
| HPAi | ENSG00000113580, Low tissue specificity |
Interactioni
Subunit structurei
Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:21730050). 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 (By similarity). 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 (PubMed:29127155). Directly interacts with UNC45A (PubMed:16478993). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and STAT5B homodimers and heterodimers (By similarity).
Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (By similarity).
Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (PubMed:10866662, PubMed:12151000, PubMed:12686538, PubMed:9154805, PubMed:9590696). Interaction with BAG1 inhibits transactivation (PubMed:10477749).
Interacts with HEXIM1, PELP1 and TGFB1I1 (PubMed:12415108, PubMed:15211577, PubMed:15941832).
Interacts with NCOA1 (PubMed:9590696).
Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity).
Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (PubMed:19141540, PubMed:21980503, PubMed:22170608).
Interacts with CIART (By similarity).
Interacts with RWDD3 (By similarity).
Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity).
Interacts with GRIP1 (PubMed:15769988, PubMed:17635946).
Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (PubMed:15591535). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (PubMed:25775514).
Interacts with GSK3B (PubMed:18838540).
Interacts with FNIP1 and FNIP2 (PubMed:27353360).
Interacts (via C-terminus) with HNRNPU (via C-terminus) (PubMed:9353307).
Interacts with MCM3AP (PubMed:16914116).
Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (PubMed:20078863).
By similarity24 PublicationsBinary interactionsi
Hide detailsP04150
Isoform Alpha [P04150-1]
| With | #Exp. | IntAct |
|---|---|---|
| Ncoa2 [Q61026] from Mus musculus. | 3 | EBI-15750116,EBI-688662 |
GO - Molecular functioni
- Hsp90 protein binding Source: UniProtKB
- protein kinase binding Source: ARUK-UCL
- repressing transcription factor binding Source: GO_Central
Protein-protein interaction databases
| BioGRIDi | 109165, 812 interactors |
| CORUMi | P04150 |
| DIPi | DIP-576N |
| ELMi | P04150 |
| IntActi | P04150, 78 interactors |
| MINTi | P04150 |
| STRINGi | 9606.ENSP00000231509 |
Chemistry databases
| BindingDBi | P04150 |
Miscellaneous databases
| RNActi | P04150, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| SMRi | P04150 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | P04150 |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 524 – 758 | NR LBDPROSITE-ProRule annotationAdd BLAST | 235 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 1 – 420 | ModulatingAdd BLAST | 420 | |
| Regioni | 98 – 115 | Required for high transcriptional activity of isoform Alpha-C31 PublicationAdd BLAST | 18 | |
| Regioni | 485 – 777 | Interaction with CLOCKAdd BLAST | 293 | |
| Regioni | 487 – 523 | HingeAdd BLAST | 37 | |
| Regioni | 532 – 697 | Interaction with CRY11 PublicationAdd BLAST | 166 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 399 – 418 | Glu/Pro/Ser/Thr-rich (PEST region)Add BLAST | 20 |
Domaini
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain (PubMed:3841189). The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required (PubMed:25847991).2 Publications
Sequence similaritiesi
Zinc finger
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Zinc fingeri | 421 – 441 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 21 | |
| Zinc fingeri | 457 – 476 | NR C4-typePROSITE-ProRule annotationAdd BLAST | 20 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
| eggNOGi | KOG3575, Eukaryota |
| GeneTreei | ENSGT00940000156385 |
| HOGENOMi | CLU_020317_0_0_1 |
| InParanoidi | P04150 |
| KOi | K05771 |
| OMAi | LSFCFQT |
| PhylomeDBi | P04150 |
| TreeFami | TF106510 |
Family and domain databases
| DisProti | DP00030 |
| Gene3Di | 1.10.565.10, 1 hit 3.30.50.10, 1 hit |
| IDEALi | IID00014 |
| InterProi | View protein in InterPro IPR001409, Glcrtcd_rcpt IPR035500, NHR-like_dom_sf IPR000536, Nucl_hrmn_rcpt_lig-bd IPR001723, Nuclear_hrmn_rcpt IPR001628, Znf_hrmn_rcpt IPR013088, Znf_NHR/GATA |
| Pfami | View protein in Pfam PF02155, GCR, 1 hit PF00104, Hormone_recep, 1 hit PF00105, zf-C4, 1 hit |
| PRINTSi | PR00528, GLCORTICOIDR PR00398, STRDHORMONER PR00047, STROIDFINGER |
| SMARTi | View protein in SMART SM00430, HOLI, 1 hit SM00399, ZnF_C4, 1 hit |
| SUPFAMi | SSF48508, SSF48508, 1 hit |
| PROSITEi | View protein in PROSITE PS51843, NR_LBD, 1 hit PS00031, NUCLEAR_REC_DBD_1, 1 hit PS51030, NUCLEAR_REC_DBD_2, 1 hit |
Sequences (16+)i
Sequence statusi: Complete.
This entry describes 16 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basketThis entry has 16 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
Isoform Alpha (identifier: P04150-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-A, GR-alphaA
This isoform has been chosen as the canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
10 20 30 40 50
MDSKESLTPG REENPSSVLA QERGDVMDFY KTLRGGATVK VSASSPSLAV
60 70 80 90 100
ASQSDSKQRR LLVDFPKGSV SNAQQPDLSK AVSLSMGLYM GETETKVMGN
110 120 130 140 150
DLGFPQQGQI SLSSGETDLK LLEESIANLN RSTSVPENPK SSASTAVSAA
160 170 180 190 200
PTEKEFPKTH SDVSSEQQHL KGQTGTNGGN VKLYTTDQST FDILQDLEFS
210 220 230 240 250
SGSPGKETNE SPWRSDLLID ENCLLSPLAG EDDSFLLEGN SNEDCKPLIL
260 270 280 290 300
PDTKPKIKDN GDLVLSSPSN VTLPQVKTEK EDFIELCTPG VIKQEKLGTV
310 320 330 340 350
YCQASFPGAN IIGNKMSAIS VHGVSTSGGQ MYHYDMNTAS LSQQQDQKPI
360 370 380 390 400
FNVIPPIPVG SENWNRCQGS GDDNLTSLGT LNFPGRTVFS NGYSSPSMRP
410 420 430 440 450
DVSSPPSSSS TATTGPPPKL CLVCSDEASG CHYGVLTCGS CKVFFKRAVE
460 470 480 490 500
GQHNYLCAGR NDCIIDKIRR KNCPACRYRK CLQAGMNLEA RKTKKKIKGI
510 520 530 540 550
QQATTGVSQE TSENPGNKTI VPATLPQLTP TLVSLLEVIE PEVLYAGYDS
560 570 580 590 600
SVPDSTWRIM TTLNMLGGRQ VIAAVKWAKA IPGFRNLHLD DQMTLLQYSW
610 620 630 640 650
MFLMAFALGW RSYRQSSANL LCFAPDLIIN EQRMTLPCMY DQCKHMLYVS
660 670 680 690 700
SELHRLQVSY EEYLCMKTLL LLSSVPKDGL KSQELFDEIR MTYIKELGKA
710 720 730 740 750
IVKREGNSSQ NWQRFYQLTK LLDSMHEVVE NLLNYCFQTF LDKTMSIEFP
760 770
EMLAEIITNQ IPKYSNGNIK KLLFHQK
Note: Predominant physiological form.1 Publication
Isoform Beta (identifier: P04150-2) [UniParc]FASTAAdd to basket
Also known as: Beta-A
The sequence of this isoform differs from the canonical sequence as follows:
728-777: VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK → NVMWLKPESTSHTLI
Note: High constitutive expression by neutrophils may provide a mechanism by which these cells escape glucocorticoid-induced cell death and up-regulation by proinflammatory cytokines such as IL8 further enhances their survival in the presence of glucocorticoids during inflammation.1 Publication
Show »Isoform Alpha-2 (identifier: P04150-3) [UniParc]FASTAAdd to basket
Also known as: Gamma
The sequence of this isoform differs from the canonical sequence as follows:
451-451: G → GR
Note: Due to a partial intron retention.Curated
Show »Isoform Beta-2 (identifier: P04150-6) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
451-451: G → GR
728-777: VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK → NVMWLKPESTSHTLI
Note: Due to a partial intron retention.Curated
Show »Isoform GR-A alpha (identifier: P04150-5) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
491-674: Missing.
Note: Lacks exons 5, 6 and 7. Found in glucocorticoid-resistant myeloma patients.1 Publication
Show »Isoform GR-A beta (identifier: P04150-7) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
491-674: Missing.
728-777: VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK → NVMWLKPESTSHTLI
Note: Lacks exons 5, 6 and 7.1 Publication
Show »Isoform GR-P (identifier: P04150-4)
Sequence is not available
Note: Encoded by exons 2-7 plus several basepairs from the subsequent intron region. Lacks the ligand binding domain. Accounts for up to 10-20% of mRNAs.1 Publication
Length:–
Mass (Da):–
Isoform Alpha-B (identifier: P04150-8) [UniParc]FASTAAdd to basket
Also known as: GR-alphaB
The sequence of this isoform differs from the canonical sequence as follows:
1-26: Missing.
Isoform Beta-B (identifier: P04150-9) [UniParc]FASTAAdd to basket
The sequence of this isoform differs from the canonical sequence as follows:
1-26: Missing.
728-777: VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK → NVMWLKPESTSHTLI
Isoform 10 (identifier: P04150-10) [UniParc]FASTAAdd to basket
Also known as: hGRDelta313-338
The sequence of this isoform differs from the canonical sequence as follows:
313-338: Missing.
Isoform Alpha-C1 (identifier: P04150-11) [UniParc]FASTAAdd to basket
Also known as: GR-alphaC1
The sequence of this isoform differs from the canonical sequence as follows:
1-85: Missing.
Isoform Alpha-C2 (identifier: P04150-12) [UniParc]FASTAAdd to basket
Also known as: GR-alphaC2
The sequence of this isoform differs from the canonical sequence as follows:
1-89: Missing.
Isoform Alpha-C3 (identifier: P04150-13) [UniParc]FASTAAdd to basket
Also known as: GR-alphaC3
The sequence of this isoform differs from the canonical sequence as follows:
1-97: Missing.
Isoform Alpha-D1 (identifier: P04150-14) [UniParc]FASTAAdd to basket
Also known as: GR-alphaD1
The sequence of this isoform differs from the canonical sequence as follows:
1-315: Missing.
Isoform Alpha-D2 (identifier: P04150-15) [UniParc]FASTAAdd to basket
Also known as: GR-alphaD2
The sequence of this isoform differs from the canonical sequence as follows:
1-330: Missing.
Isoform Alpha-D3 (identifier: P04150-16) [UniParc]FASTAAdd to basket
Also known as: GR-alphaD3
The sequence of this isoform differs from the canonical sequence as follows:
1-335: Missing.
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| A0A494C0P1 | A0A494C0P1_HUMAN | Glucocorticoid receptor | NR3C1 | 746 | Annotation score: | ||
| D6RDA9 | D6RDA9_HUMAN | Glucocorticoid receptor | NR3C1 | 144 | Annotation score: | ||
| Q3MSN4 | Q3MSN4_HUMAN | Glucocorticoid receptor | NR3C1 | 145 | Annotation score: |
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 399 | R → G in BAD97314 (Ref. 7) Curated | 1 | |
| Sequence conflicti | 754 | A → T in BAD97314 (Ref. 7) Curated | 1 |
Polymorphismi
Carriers of the 22-Glu-Lys-23 allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than non-carriers, resulting in a better metabolic health profile. Carriers have a better survival than non-carriers, as well as lower serum CRP levels. The 22-Glu-Lys-23 polymorphism is associated with a sex-specific, beneficial body composition at young-adult age, as well as greater muscle strength in males.
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_014140 | 23 | R → K Polymorphism; reduces transactivation activity; does not affect transrepression activity. 8 PublicationsCorresponds to variant dbSNP:rs6190EnsemblClinVar. | 1 | |
| Natural variantiVAR_015628 | 29 | F → L1 PublicationCorresponds to variant dbSNP:rs148102613Ensembl. | 1 | |
| Natural variantiVAR_014622 | 65 | F → V2 PublicationsCorresponds to variant dbSNP:rs6192EnsemblClinVar. | 1 | |
| Natural variantiVAR_075797 | 72 | N → D Polymorphism; associated in cis with A-321 and S-766 in one individual; doubles transactivation potential. 1 Publication | 1 | |
| Natural variantiVAR_015629 | 112 | L → F1 PublicationCorresponds to variant dbSNP:rs542110718Ensembl. | 1 | |
| Natural variantiVAR_015630 | 233 | D → N1 PublicationCorresponds to variant dbSNP:rs1241576112Ensembl. | 1 | |
| Natural variantiVAR_075798 | 321 | V → A Polymorphism; associated in cis with D-72 and S-766 in one individual; doubles transactivation potential. 1 Publication | 1 | |
| Natural variantiVAR_004675 | 363 | N → S Enhances transactivation activity; does not affect transrepression activity; may increase sensitivity to exogenously administered glucocorticoids; may contribute to central obesity in men and show lack of association with other risk factors for coronary heart disease and diabetes mellitus. 6 PublicationsCorresponds to variant dbSNP:rs56149945EnsemblClinVar. | 1 | |
| Natural variantiVAR_015631 | 421 | C → Y1 Publication | 1 | |
| Natural variantiVAR_075799 | 423 | V → A in GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_013472 | 477 | R → H in GCCR. 1 PublicationCorresponds to variant dbSNP:rs104893913EnsemblClinVar. | 1 | |
| Natural variantiVAR_077143 | 477 | R → S in GCCR; loss of DNA-binding and of transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type. 1 Publication | 1 | |
| Natural variantiVAR_077144 | 478 | Y → C in GCCR; decreased DNA-binding and transactivation activity; incomplete dexamethasone-induced translocation to the nucleus; no effect on dexamethasone-binding affinity compared with wild-type. 1 Publication | 1 | |
| Natural variantiVAR_075800 | 556 | T → I in GCCR; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. 2 Publications | 1 | |
| Natural variantiVAR_015632 | 559 | I → N in GCCR; interferes with translocation to the nucleus and thereby strongly reduces transcription activation; is equally impaired in nuclear export; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs104893909EnsemblClinVar. | 1 | |
| Natural variantiVAR_025014 | 571 | V → A in pseudohermaphroditism; female with hypokalemia due to glucocorticoid resistance; 6-fold reduction in binding affinity compared with the wild-type receptor. 1 PublicationCorresponds to variant dbSNP:rs104893911EnsemblClinVar. | 1 | |
| Natural variantiVAR_075801 | 575 | V → G in GCCR; unknown pathological significance; reduces transactivation activity; enhances transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not exert a dominant negative effect; does not impair DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_004676 | 641 | D → V in GCCR. 1 PublicationCorresponds to variant dbSNP:rs104893908EnsemblClinVar. | 1 | |
| Natural variantiVAR_077145 | 672 | L → P in GCCR; loss of dexamethasone-binding, dexamethasone-induced translocation to the nucleus and of transactivation activity. 1 Publication | 1 | |
| Natural variantiVAR_013473 | 679 | G → S in GCCR; has 50% binding affinity. 1 PublicationCorresponds to variant dbSNP:rs104893914EnsemblClinVar. | 1 | |
| Natural variantiVAR_075802 | 714 | R → Q in GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_075803 | 726 | H → R in GCCR; unknown pathological significance; reduces transactivation and transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not impair DNA binding. 1 Publication | 1 | |
| Natural variantiVAR_004677 | 729 | V → I in GCCR. 1 PublicationCorresponds to variant dbSNP:rs1027058734Ensembl. | 1 | |
| Natural variantiVAR_071935 | 737 | F → L in GCCR; reduces transactivation of the glucocorticoid-inducible tumor virus promoter; reduces affinity for ligand; delays its nuclear translocation; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs121909727EnsemblClinVar. | 1 | |
| Natural variantiVAR_015633 | 747 | I → M in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs104893910EnsemblClinVar. | 1 | |
| Natural variantiVAR_004678 | 753 | L → F2 PublicationsCorresponds to variant dbSNP:rs121909726EnsemblClinVar. | 1 | |
| Natural variantiVAR_075804 | 766 | N → S Polymorphism; associated in cis with D-72 and A-321 in one individual; doubles transactivation potential. 1 Publication | 1 | |
| Natural variantiVAR_071936 | 773 | L → P in GCCR; reduces transactivation of the glucocorticoid-inducible tumor virus promoter; reduces affinity for ligand; delays its nuclear translocation; acts as dominant negative mutant. 1 PublicationCorresponds to variant dbSNP:rs104893912EnsemblClinVar. | 1 |
Alternative sequence
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Alternative sequenceiVSP_058312 | 1 – 335 | Missing in isoform Alpha-D3. 1 PublicationAdd BLAST | 335 | |
| Alternative sequenceiVSP_058313 | 1 – 330 | Missing in isoform Alpha-D2. 1 PublicationAdd BLAST | 330 | |
| Alternative sequenceiVSP_058314 | 1 – 315 | Missing in isoform Alpha-D1. 1 PublicationAdd BLAST | 315 | |
| Alternative sequenceiVSP_058315 | 1 – 97 | Missing in isoform Alpha-C3. 1 PublicationAdd BLAST | 97 | |
| Alternative sequenceiVSP_058316 | 1 – 89 | Missing in isoform Alpha-C2. 1 PublicationAdd BLAST | 89 | |
| Alternative sequenceiVSP_058317 | 1 – 85 | Missing in isoform Alpha-C1. 1 PublicationAdd BLAST | 85 | |
| Alternative sequenceiVSP_018773 | 1 – 26 | Missing in isoform Alpha-B and isoform Beta-B. CuratedAdd BLAST | 26 | |
| Alternative sequenceiVSP_043908 | 313 – 338 | Missing in isoform 10. 1 PublicationAdd BLAST | 26 | |
| Alternative sequenceiVSP_007363 | 451 | G → GR in isoform Alpha-2 and isoform Beta-2. 1 Publication | 1 | |
| Alternative sequenceiVSP_013340 | 491 – 674 | Missing in isoform GR-A alpha and isoform GR-A beta. CuratedAdd BLAST | 184 | |
| Alternative sequenceiVSP_003703 | 728 – 777 | VVENL…LFHQK → NVMWLKPESTSHTLI in isoform Beta, isoform Beta-B, isoform Beta-2 and isoform GR-A beta. 1 PublicationAdd BLAST | 50 |
Sequence databases
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative initiation, Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Web resourcesi
| NIEHS-SNPs |
| Wikipedia Glucocorticoid receptor entry |
Sequence databases
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1M2Z | X-ray | 2.50 | A/D | 521-777 | [»] | |
| 1NHZ | X-ray | 2.30 | A | 500-777 | [»] | |
| 1P93 | X-ray | 2.70 | A/B/C/D | 500-777 | [»] | |
| 3BQD | X-ray | 2.50 | A | 525-777 | [»] | |
| 3CLD | X-ray | 2.84 | A/B | 521-777 | [»] | |
| 3E7C | X-ray | 2.15 | A/B | 521-777 | [»] | |
| 3H52 | X-ray | 2.80 | A/B/C/D | 528-777 | [ |