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Protein

Glucocorticoid receptor

Gene

NR3C1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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: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 similarity2 Publications
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).By similarity11 Publications
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).By similarity5 Publications
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.1 Publication
Isoform Alpha-B: More effective than isoform Alpha in transcriptional activation, but not repression activity.2 Publications
Isoform 10: Has transcriptional activation activity.1 Publication
Isoform Alpha-C1: Has transcriptional activation activity.1 Publication
Isoform Alpha-C2: Has transcriptional activation activity.1 Publication
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).3 Publications
Isoform Alpha-D1: Has transcriptional activation activity.1 Publication
Isoform Alpha-D2: Has transcriptional activation activity.1 Publication
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).3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi418 – 49376Nuclear receptorPROSITE-ProRule annotationAdd
BLAST
Zinc fingeri421 – 44121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri457 – 47620NR C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • glucocorticoid-activated RNA polymerase II transcription factor binding transcription factor activity Source: UniProtKB
  • glucocorticoid receptor activity Source: ProtInc
  • RNA binding Source: UniProtKB-KW
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • steroid binding Source: UniProtKB
  • steroid hormone binding Source: UniProtKB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: UniProtKB
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cellular response to steroid hormone stimulus Source: UniProtKB
  • chromatin modification Source: UniProtKB-KW
  • chromosome segregation Source: UniProtKB-KW
  • mitotic nuclear division Source: UniProtKB-KW
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • signal transduction Source: ProtInc
  • transcription, DNA-templated Source: ProtInc
  • transcription from RNA polymerase II promoter Source: ProtInc
  • transcription initiation from RNA polymerase II promoter Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Receptor

Keywords - Biological processi

Apoptosis, Cell cycle, Cell division, Chromosome partition, Mitosis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Lipid-binding, Metal-binding, RNA-binding, Steroid-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-383280. Nuclear Receptor transcription pathway.
R-HSA-8849473. PTK6 Expression.
SignaLinkiP04150.
SIGNORiP04150.

Names & Taxonomyi

Protein namesi
Recommended name:
Glucocorticoid receptor
Short name:
GR
Alternative name(s):
Nuclear receptor subfamily 3 group C member 1
Gene namesi
Name:NR3C1
Synonyms:GRL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:7978. NR3C1.

Subcellular locationi

Isoform Alpha :
Isoform Beta :
Isoform Alpha-B :
  • Nucleus 1 Publication
  • Cytoplasm 1 Publication

  • Note: After ligand activation, translocates from the cytoplasm to the nucleus.1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • microtubule organizing center Source: UniProtKB-SubCell
  • mitochondrial matrix Source: ProtInc
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • spindle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Glucocorticoid resistance, generalized (GCCR)8 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.
See also OMIM:615962
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti423 – 4231V → A in GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. 1 Publication
VAR_075799
Natural varianti477 – 4771R → H in GCCR. 1 Publication
Corresponds to variant rs104893913 [ dbSNP | Ensembl ].
VAR_013472
Natural varianti556 – 5561T → 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
VAR_075800
Natural varianti559 – 5591I → 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 Publication
Corresponds to variant rs104893909 [ dbSNP | Ensembl ].
VAR_015632
Natural varianti575 – 5751V → 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
VAR_075801
Natural varianti641 – 6411D → V in GCCR. 1 Publication
Corresponds to variant rs104893908 [ dbSNP | Ensembl ].
VAR_004676
Natural varianti679 – 6791G → S in GCCR; has 50% binding affinity. 1 Publication
Corresponds to variant rs104893914 [ dbSNP | Ensembl ].
VAR_013473
Natural varianti714 – 7141R → Q in GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. 1 Publication
VAR_075802
Natural varianti726 – 7261H → 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
VAR_075803
Natural varianti729 – 7291V → I in GCCR. 1 Publication
VAR_004677
Natural varianti737 – 7371F → 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 Publication
Corresponds to variant rs121909727 [ dbSNP | Ensembl ].
VAR_071935
Natural varianti747 – 7471I → M in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. 1 Publication
Corresponds to variant rs104893910 [ dbSNP | Ensembl ].
VAR_015633
Natural varianti773 – 7731L → 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 Publication
Corresponds to variant rs104893912 [ dbSNP | Ensembl ].
VAR_071936

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11M → T: Abolishes expression of A-type isoforms. 2 Publications
Mutagenesisi27 – 271M → T: Abolishes expression of B-type isoforms. 2 Publications
Mutagenesisi86 – 861M → I: Abolishes expression of C-type isoforms; when associated with I-90 and I-98. 1 Publication
Mutagenesisi90 – 901M → I: Abolishes expression of C-type isoforms; when associated with I-86 and I-98. 1 Publication
Mutagenesisi98 – 981M → I: Abolishes expression of C-type isoforms; when associated with I-86 and I-90. 1 Publication
Mutagenesisi101 – 1011D → A: Reduces transcription activation activity of isoform Alpha-C3 by half. 1 Publication
Mutagenesisi101 – 1011D → 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
Mutagenesisi106 – 1072QQ → LL: Reduces activity of isoform Alpha-C3 by half. 1 Publication
Mutagenesisi113 – 1142SS → AA: Does not affect the activity of isoform Alpha-C3. 1 Publication
Mutagenesisi191 – 1911F → D: Reduces transactivation by the ADA complex. 1 Publication
Mutagenesisi193 – 1931I → D: Reduces transactivation by the ADA complex. 1 Publication
Mutagenesisi194 – 1941L → A: Strongly reduces transactivation by the ADA complex; when associated with V-224 and F-225. 1 Publication
Mutagenesisi197 – 1971L → E: Reduces transactivation by the ADA complex. 1 Publication
Mutagenesisi211 – 2111S → A: Reduces expression of target genes IGFBP1 and IRF8. 1 Publication
Mutagenesisi213 – 2131W → A: Strongly reduces transactivation by the ADA complex. 1 Publication
Mutagenesisi224 – 2241L → V: Strongly reduces transactivation by the ADA complex; when associated with A-194 and F-225. 1 Publication
Mutagenesisi225 – 2251L → F: Strongly reduces transactivation by the ADA complex; when associated with A-194 and V-224. 1 Publication
Mutagenesisi226 – 2261S → A: Abolishes phosphorylation and enhances transcriptional activation. 1 Publication
Mutagenesisi235 – 2351F → L: Strongly reduces transactivation by the ADA complex; when associated with V-236. 1 Publication
Mutagenesisi236 – 2361L → V: Strongly reduces transactivation by the ADA complex; when associated with L-235. 1 Publication
Mutagenesisi277 – 2771K → R: Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-293. 1 Publication
Mutagenesisi293 – 2931K → R: Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-277. 1 Publication
Mutagenesisi316 – 3161M → I: Abolishes expression of D-type isoforms; when associated with I-331 and I-336. 1 Publication
Mutagenesisi331 – 3311M → I: Abolishes expression of D-type isoforms; when associated with I-316 and I-336. 1 Publication
Mutagenesisi336 – 3361M → I: Abolishes expression of D-type isoforms; when associated with I-316 and I-331. 1 Publication
Mutagenesisi404 – 4041S → 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
Mutagenesisi404 – 4041S → D: Does not affect translocation to the nucleus following ligand stimulation. 1 Publication
Mutagenesisi480 – 4801K → 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
Mutagenesisi492 – 4921K → 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
Mutagenesisi494 – 4941K → 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
Mutagenesisi495 – 4951K → 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
Mutagenesisi585 – 5851R → A: Reduces activation mediated by ligand binding domain; when associated with A-590. 1 Publication
Mutagenesisi590 – 5901D → A: Reduces activation mediated by ligand binding domain; when associated with A-585. 1 Publication
Mutagenesisi602 – 6021F → S: Increases solubility. No effect on transactivation by dexamethasone. 1 Publication
Mutagenesisi625 – 6251P → A: Decreases transactivation by dexamethasone by 95%. 1 Publication
Mutagenesisi628 – 6281I → A: Decreases dimerization and transactivation by dexamethasone; when associated with S-602. 1 Publication
Mutagenesisi703 – 7031K → R: Slightly reduces sumoylation. Inhibits the stimulatory effect of RWDD3 on its transcriptional activity. 2 Publications

Keywords - Diseasei

Disease mutation, Pseudohermaphroditism

Organism-specific databases

MalaCardsiNR3C1.
MIMi615962. phenotype.
Orphaneti786. Glucocorticoid resistance.
PharmGKBiPA181.

Chemistry

ChEMBLiCHEMBL2034.
DrugBankiDB00240. Alclometasone.
DB00288. Amcinonide.
DB00394. Beclomethasone.
DB00443. Betamethasone.
DB01222. Budesonide.
DB01410. Ciclesonide.
DB01013. Clobetasol propionate.
DB00838. Clocortolone.
DB01380. Cortisone acetate.
DB01260. Desonide.
DB00547. Desoximetasone.
DB01234. Dexamethasone.
DB00223. Diflorasone.
DB06781. Difluprednate.
DB00687. Fludrocortisone.
DB00663. Flumethasone.
DB00180. Flunisolide.
DB00591. Fluocinolone Acetonide.
DB01047. Fluocinonide.
DB00324. Fluorometholone.
DB01185. Fluoxymesterone.
DB00846. Flurandrenolide.
DB08906. Fluticasone furoate.
DB00588. Fluticasone Propionate.
DB00596. Halobetasol Propionate.
DB00769. Hydrocortamate.
DB00741. Hydrocortisone.
DB00873. Loteprednol.
DB00253. Medrysone.
DB00351. Megestrol acetate.
DB00959. Methylprednisolone.
DB00834. Mifepristone.
DB00764. Mometasone.
DB01384. Paramethasone.
DB01130. Prednicarbate.
DB00860. Prednisolone.
DB00635. Prednisone.
DB00896. Rimexolone.
DB00421. Spironolactone.
DB00620. Triamcinolone.
DB08867. Ulipristal.
GuidetoPHARMACOLOGYi625.

Polymorphism and mutation databases

BioMutaiNR3C1.
DMDMi121069.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 777777Glucocorticoid receptorPRO_0000019937Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei8 – 81PhosphothreonineCombined sources
Modified residuei45 – 451PhosphoserineCombined sources
Modified residuei113 – 1131PhosphoserineBy similarity
Modified residuei134 – 1341PhosphoserineCombined sources
Modified residuei141 – 1411PhosphoserineBy similarity
Modified residuei203 – 2031PhosphoserineCombined sources3 Publications
Modified residuei211 – 2111Phosphoserine3 Publications
Modified residuei226 – 2261PhosphoserineCombined sources1 Publication
Modified residuei267 – 2671PhosphoserineCombined sources
Cross-linki277 – 277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki293 – 293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki293 – 293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei404 – 4041Phosphoserine; by GSK3-beta1 Publication
Modified residuei480 – 4801N6-acetyllysine1 Publication
Modified residuei492 – 4921N6-acetyllysine1 Publication
Modified residuei494 – 4941N6-acetyllysine1 Publication
Modified residuei495 – 4951N6-acetyllysine1 Publication
Cross-linki703 – 703Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Isoform Alpha-B (identifier: P04150-8)
Modified residuei1 – 11N-acetylmethionineCombined sources
Isoform Beta-B (identifier: P04150-9)
Modified residuei1 – 11N-acetylmethionineCombined sources1 Publication

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, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP04150.
MaxQBiP04150.
PaxDbiF5ATB7.
P04150.
PeptideAtlasiP04150.
PRIDEiP04150.

PTM databases

iPTMnetiP04150.
PhosphoSiteiP04150.

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

BgeeiENSG00000113580.
CleanExiHS_NR3C1.
ExpressionAtlasiP04150. baseline and differential.
GenevisibleiP04150. HS.

Organism-specific databases

HPAiCAB010435.
HPA004248.

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). 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).By similarity19 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AKT1P317495EBI-493507,EBI-296087
Asxl1P595982EBI-493507,EBI-5743705From a different organism.
CAV1Q031352EBI-493507,EBI-603614
CD4P017302EBI-493507,EBI-353826
EGFRP005332EBI-493507,EBI-297353
HNF4AP412352EBI-493507,EBI-1049011
HSP90AA1P079007EBI-493507,EBI-296047
KIAA0408Q6ZU522EBI-493507,EBI-739493
LCKP062393EBI-493507,EBI-1348
MvpQ626672EBI-493507,EBI-918333From a different organism.
TMF1P820943EBI-493507,EBI-949763

Protein-protein interaction databases

BioGridi109165. 161 interactions.
DIPiDIP-576N.
IntActiP04150. 73 interactions.
MINTiMINT-150603.
STRINGi9606.ENSP00000231509.

Chemistry

BindingDBiP04150.

Structurei

Secondary structure

1
777
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni422 – 4243Combined sources
Beta strandi430 – 4323Combined sources
Beta strandi435 – 4373Combined sources
Helixi439 – 44911Combined sources
Beta strandi458 – 4614Combined sources
Turni467 – 4726Combined sources
Helixi474 – 48411Combined sources
Turni525 – 5273Combined sources
Helixi532 – 5387Combined sources
Beta strandi550 – 5523Combined sources
Helixi556 – 57924Combined sources
Helixi584 – 5863Combined sources
Helixi589 – 61527Combined sources
Beta strandi617 – 6193Combined sources
Beta strandi621 – 6244Combined sources
Beta strandi627 – 6293Combined sources
Helixi631 – 6344Combined sources
Helixi639 – 65517Combined sources
Helixi660 – 67112Combined sources
Beta strandi673 – 6753Combined sources
Helixi683 – 70220Combined sources
Beta strandi704 – 7063Combined sources
Helixi708 – 74134Combined sources
Helixi743 – 7453Combined sources
Helixi751 – 76515Combined sources
Beta strandi769 – 7713Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M2ZX-ray2.50A/D521-777[»]
1NHZX-ray2.30A500-777[»]
1P93X-ray2.70A/B/C/D500-777[»]
3BQDX-ray2.50A525-777[»]
3CLDX-ray2.84A/B521-777[»]
3E7CX-ray2.15A/B521-777[»]
3H52X-ray2.80A/B/C/D528-777[»]
3K22X-ray2.10A/B521-777[»]
3K23X-ray3.00A/B/C521-777[»]
4CSJX-ray2.30A500-777[»]
4HN5X-ray1.90A/B417-506[»]
4HN6X-ray2.55A/B417-506[»]
4LSJX-ray2.35A522-777[»]
4MDDX-ray2.40A/B522-777[»]
4P6WX-ray1.95A526-777[»]
4P6XX-ray2.50A/C/E/G/I/K523-777[»]
4UDCX-ray2.50A500-777[»]
4UDDX-ray1.80A500-777[»]
5CBXX-ray2.00A/B/E/F415-495[»]
5CBYX-ray2.00A/B415-495[»]
5CBZX-ray2.20A/B/E/F419-495[»]
5CC1X-ray2.30A/B/W/X417-506[»]
DisProtiDP00030.
ProteinModelPortaliP04150.
SMRiP04150. Positions 418-777.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04150.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 420420ModulatingAdd
BLAST
Regioni98 – 11518Required for high transcriptional activity of isoform Alpha-C31 PublicationAdd
BLAST
Regioni485 – 777293Interaction with CLOCKAdd
BLAST
Regioni487 – 52741HingeAdd
BLAST
Regioni528 – 777250Steroid-bindingAdd
BLAST
Regioni532 – 697166Interaction with CRY1Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi399 – 41820Glu/Pro/Ser/Thr-rich (PEST region)Add
BLAST

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

Contains 1 nuclear receptor DNA-binding domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri421 – 44121NR C4-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri457 – 47620NR C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000037950.
HOVERGENiHBG007583.
InParanoidiP04150.
KOiK05771.
OMAiQSTFDIL.
PhylomeDBiP04150.
TreeFamiTF106510.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR001409. Glcrtcd_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF02155. GCR. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00528. GLCORTICOIDR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]

Sequences (16)i

Sequence statusi: Complete.

This entry describes 16 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform Alpha (identifier: P04150-1) [UniParc]FASTAAdd to basket
Also known as: Alpha-A, GR-alphaA

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:777
Mass (Da):85,659
Last modified:November 1, 1986 - v1
Checksum:iC5C90C9A5DD16AAB
GO
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

Show »
Length:742
Mass (Da):81,509
Checksum:iE2D1F6EA0EE14704
GO
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.
Show »
Length:778
Mass (Da):85,815
Checksum:i23048D99B60B169C
GO
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.
Show »
Length:743
Mass (Da):81,666
Checksum:i329BE98BCC1DC0E5
GO
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 »
Length:593
Mass (Da):64,752
Checksum:i8CB72DE6B0593EFD
GO
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 »
Length:558
Mass (Da):60,602
Checksum:i7C1C30CD84689FBE
GO
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.

Note: Produced by alternative initiation at Met-27 of isoform Alpha.Combined sources
Show »
Length:751
Mass (Da):82,845
Checksum:iC6D7A2D88B4025C1
GO
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

Note: Produced by alternative initiation at Met-27 of isoform Beta.Combined sources1 Publication
Show »
Length:716
Mass (Da):78,695
Checksum:iBCF1D97EFD06AB74
GO
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.

Show »
Length:751
Mass (Da):82,904
Checksum:i39C4B6A962632545
GO
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.

Note: Produced by alternative initiation at Met-86 of isoform Alpha.1 Publication
Show »
Length:692
Mass (Da):76,650
Checksum:iF73B43BE6F312683
GO
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.

Note: Produced by alternative initiation at Met-90 of isoform Alpha.1 Publication
Show »
Length:688
Mass (Da):76,186
Checksum:i7A51C90C4FAC4A95
GO
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.

Note: Produced by alternative initiation at Met-98 of isoform Alpha.1 Publication
Show »
Length:680
Mass (Da):75,310
Checksum:iF56474496CCAB832
GO
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.

Note: Produced by alternative initiation at Met-316 of isoform Alpha.1 Publication
Show »
Length:462
Mass (Da):51,912
Checksum:i25B86AA2128DA764
GO
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.

Note: Produced by alternative initiation at Met-331 of isoform Alpha.1 Publication
Show »
Length:447
Mass (Da):50,512
Checksum:i5FD4D80AFE4572D1
GO
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.

Note: Produced by alternative initiation at Met-336 of isoform Alpha.1 Publication
Show »
Length:442
Mass (Da):49,802
Checksum:iFE52994682DE7E41
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti399 – 3991R → G in BAD97314 (Ref. 7) Curated
Sequence conflicti754 – 7541A → T in BAD97314 (Ref. 7) Curated

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti23 – 231R → K Polymorphism; reduces transactivation activity; does not affect transrepression activity. 8 Publications
Corresponds to variant rs6190 [ dbSNP | Ensembl ].
VAR_014140
Natural varianti29 – 291F → L.1 Publication
Corresponds to variant rs148102613 [ dbSNP | Ensembl ].
VAR_015628
Natural varianti65 – 651F → V.2 Publications
Corresponds to variant rs6192 [ dbSNP | Ensembl ].
VAR_014622
Natural varianti72 – 721N → D Polymorphism; associated in cis with A-321 and S-766 in one individual; doubles transactivation potential. 1 Publication
VAR_075797
Natural varianti112 – 1121L → F.1 Publication
Corresponds to variant rs542110718 [ dbSNP | Ensembl ].
VAR_015629
Natural varianti233 – 2331D → N.1 Publication
VAR_015630
Natural varianti321 – 3211V → A Polymorphism; associated in cis with D-72 and S-766 in one individual; doubles transactivation potential. 1 Publication
VAR_075798
Natural varianti363 – 3631N → 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 Publications
Corresponds to variant rs6195 [ dbSNP | Ensembl ].
VAR_004675
Natural varianti421 – 4211C → Y in a glucocorticoid resistant leukemia cell line. 1 Publication
VAR_015631
Natural varianti423 – 4231V → A in GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. 1 Publication
VAR_075799
Natural varianti477 – 4771R → H in GCCR. 1 Publication
Corresponds to variant rs104893913 [ dbSNP | Ensembl ].
VAR_013472
Natural varianti556 – 5561T → 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
VAR_075800
Natural varianti559 – 5591I → 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 Publication
Corresponds to variant rs104893909 [ dbSNP | Ensembl ].
VAR_015632
Natural varianti571 – 5711V → A in pseudohermaphroditism; female with hypokalemia due to glucocorticoid resistance; 6-fold reduction in binding affinity compared with the wild-type receptor. 1 Publication
Corresponds to variant rs104893911 [ dbSNP | Ensembl ].
VAR_025014
Natural varianti575 – 5751V → 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
VAR_075801
Natural varianti641 – 6411D → V in GCCR. 1 Publication
Corresponds to variant rs104893908 [ dbSNP | Ensembl ].
VAR_004676
Natural varianti679 – 6791G → S in GCCR; has 50% binding affinity. 1 Publication
Corresponds to variant rs104893914 [ dbSNP | Ensembl ].
VAR_013473
Natural varianti714 – 7141R → Q in GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. 1 Publication
VAR_075802
Natural varianti726 – 7261H → 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
VAR_075803
Natural varianti729 – 7291V → I in GCCR. 1 Publication
VAR_004677
Natural varianti737 – 7371F → 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 Publication
Corresponds to variant rs121909727 [ dbSNP | Ensembl ].
VAR_071935
Natural varianti747 – 7471I → M in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. 1 Publication
Corresponds to variant rs104893910 [ dbSNP | Ensembl ].
VAR_015633
Natural varianti753 – 7531L → F in two glucocorticoid resistant leukemia cell lines lacking the normal allele. 2 Publications
Corresponds to variant rs121909726 [ dbSNP | Ensembl ].
VAR_004678
Natural varianti766 – 7661N → S Polymorphism; associated in cis with D-72 and A-321 in one individual; doubles transactivation potential. 1 Publication
VAR_075804
Natural varianti773 – 7731L → 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 Publication
Corresponds to variant rs104893912 [ dbSNP | Ensembl ].
VAR_071936

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 335335Missing in isoform Alpha-D3. 1 PublicationVSP_058312Add
BLAST
Alternative sequencei1 – 330330Missing in isoform Alpha-D2. 1 PublicationVSP_058313Add
BLAST
Alternative sequencei1 – 315315Missing in isoform Alpha-D1. 1 PublicationVSP_058314Add
BLAST
Alternative sequencei1 – 9797Missing in isoform Alpha-C3. 1 PublicationVSP_058315Add
BLAST
Alternative sequencei1 – 8989Missing in isoform Alpha-C2. 1 PublicationVSP_058316Add
BLAST
Alternative sequencei1 – 8585Missing in isoform Alpha-C1. 1 PublicationVSP_058317Add
BLAST
Alternative sequencei1 – 2626Missing in isoform Alpha-B and isoform Beta-B. CuratedVSP_018773Add
BLAST
Alternative sequencei313 – 33826Missing in isoform 10. 1 PublicationVSP_043908Add
BLAST
Alternative sequencei451 – 4511G → GR in isoform Alpha-2 and isoform Beta-2. 1 PublicationVSP_007363
Alternative sequencei491 – 674184Missing in isoform GR-A alpha and isoform GR-A beta. CuratedVSP_013340Add
BLAST
Alternative sequencei728 – 77750VVENL…LFHQK → NVMWLKPESTSHTLI in isoform Beta, isoform Beta-B, isoform Beta-2 and isoform GR-A beta. 1 PublicationVSP_003703Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03225 mRNA. Translation: CAA26976.1.
X03348 mRNA. Translation: CAA27054.1.
U80946
, U78506, U78507, U78508, U78509, U78510, U78511, U78512 Genomic DNA. Translation: AAB64353.1.
U80947
, U78506, U78507, U78508, U78509, U78510, U78511, U78512 Genomic DNA. Translation: AAB64354.1.
HQ205546 Genomic DNA. Translation: ADP91135.1.
HQ205547 Genomic DNA. Translation: ADP91138.1.
HQ205548 Genomic DNA. Translation: ADP91141.1.
HQ205549 Genomic DNA. Translation: ADP91144.1.
HQ205550 Genomic DNA. Translation: ADP91147.1.
HQ205551 Genomic DNA. Translation: ADP91150.1.
HQ205552 Genomic DNA. Translation: ADP91153.1.
HQ205553 Genomic DNA. Translation: ADP91156.1.
HQ205554 Genomic DNA. Translation: ADP91159.1.
HQ205555 Genomic DNA. Translation: ADP91162.1.
HQ205556 Genomic DNA. Translation: ADP91165.1.
HQ205557 Genomic DNA. Translation: ADP91168.1.
HQ205558 Genomic DNA. Translation: ADP91171.1.
HQ205559 Genomic DNA. Translation: ADP91174.1.
HQ205560 Genomic DNA. Translation: ADP91177.1.
HQ205561 Genomic DNA. Translation: ADP91180.1.
HQ205562 Genomic DNA. Translation: ADP91183.1.
HQ205563 Genomic DNA. Translation: ADP91186.1.
HQ205564 Genomic DNA. Translation: ADP91189.1.
HQ205565 Genomic DNA. Translation: ADP91192.1.
HQ205566 Genomic DNA. Translation: ADP91195.1.
HQ205567 Genomic DNA. Translation: ADP91198.1.
HQ205568 Genomic DNA. Translation: ADP91201.1.
HQ205569 Genomic DNA. Translation: ADP91204.1.
HQ205570 Genomic DNA. Translation: ADP91207.1.
HQ205571 Genomic DNA. Translation: ADP91210.1.
HQ205572 Genomic DNA. Translation: ADP91213.1.
HQ205573 Genomic DNA. Translation: ADP91216.1.
HQ205574 Genomic DNA. Translation: ADP91219.1.
HQ205575 Genomic DNA. Translation: ADP91222.1.
HQ205576 Genomic DNA. Translation: ADP91225.1.
HQ205577 Genomic DNA. Translation: ADP91228.1.
HQ205578 Genomic DNA. Translation: ADP91231.1.
HQ205579 Genomic DNA. Translation: ADP91234.1.
HQ205580 Genomic DNA. Translation: ADP91237.1.
HQ205581 Genomic DNA. Translation: ADP91240.1.
HQ205582 Genomic DNA. Translation: ADP91243.1.
HQ205583 Genomic DNA. Translation: ADP91246.1.
HQ205584 Genomic DNA. Translation: ADP91249.1.
HQ205585 Genomic DNA. Translation: ADP91252.1.
AM183262 mRNA. Translation: CAJ65924.1.
HQ450643 mRNA. Translation: AED99114.1.
U01351 mRNA. Translation: AAA16603.1.
AK223594 mRNA. Translation: BAD97314.1.
BX640610 mRNA. Translation: CAE45716.1.
AY436590 Genomic DNA. Translation: AAQ97180.1.
EU332858 Genomic DNA. Translation: ABY87547.1.
AC005601 Genomic DNA. Translation: AAC34207.1.
AC004782 Genomic DNA. No translation available.
AC091925 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61872.1.
CH471062 Genomic DNA. Translation: EAW61873.1.
BC015610 mRNA. Translation: AAH15610.1.
M69104 Genomic DNA. Translation: AAA88049.1.
AH002750 Genomic DNA. Translation: AAA53151.1.
S68378 Genomic DNA. Translation: AAB20466.1.
CCDSiCCDS34258.1. [P04150-3]
CCDS4278.1. [P04150-1]
CCDS47298.1. [P04150-2]
PIRiA93370. QRHUGA.
B93370. QRHUGB.
RefSeqiNP_000167.1. NM_000176.2. [P04150-1]
NP_001018084.1. NM_001018074.1. [P04150-1]
NP_001018085.1. NM_001018075.1. [P04150-1]
NP_001018086.1. NM_001018076.1. [P04150-1]
NP_001018087.1. NM_001018077.1. [P04150-1]
NP_001018661.1. NM_001020825.1. [P04150-2]
NP_001019265.1. NM_001024094.1. [P04150-3]
NP_001191187.1. NM_001204258.1. [P04150-8]
NP_001191188.1. NM_001204259.1. [P04150-11]
NP_001191189.1. NM_001204260.1. [P04150-12]
NP_001191190.1. NM_001204261.1. [P04150-13]
NP_001191191.1. NM_001204262.1. [P04150-14]
NP_001191192.1. NM_001204263.1. [P04150-15]
NP_001191193.1. NM_001204264.1. [P04150-16]
XP_005268476.1. XM_005268419.3. [P04150-3]
XP_005268477.1. XM_005268420.4. [P04150-3]
XP_005268479.1. XM_005268422.3. [P04150-3]
XP_005268480.1. XM_005268423.3. [P04150-3]
UniGeneiHs.122926.

Genome annotation databases

EnsembliENST00000231509; ENSP00000231509; ENSG00000113580. [P04150-3]
ENST00000343796; ENSP00000343205; ENSG00000113580. [P04150-1]
ENST00000394464; ENSP00000377977; ENSG00000113580. [P04150-1]
ENST00000394466; ENSP00000377979; ENSG00000113580. [P04150-3]
ENST00000415690; ENSP00000387672; ENSG00000113580. [P04150-2]
ENST00000424646; ENSP00000405282; ENSG00000113580. [P04150-10]
ENST00000503201; ENSP00000427672; ENSG00000113580. [P04150-1]
ENST00000504572; ENSP00000422518; ENSG00000113580. [P04150-3]
GeneIDi2908.
KEGGihsa:2908.
UCSCiuc003lmy.4. human. [P04150-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

Glucocorticoid receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X03225 mRNA. Translation: CAA26976.1.
X03348 mRNA. Translation: CAA27054.1.
U80946
, U78506, U78507, U78508, U78509, U78510, U78511, U78512 Genomic DNA. Translation: AAB64353.1.
U80947
, U78506, U78507, U78508, U78509, U78510, U78511, U78512 Genomic DNA. Translation: AAB64354.1.
HQ205546 Genomic DNA. Translation: ADP91135.1.
HQ205547 Genomic DNA. Translation: ADP91138.1.
HQ205548 Genomic DNA. Translation: ADP91141.1.
HQ205549 Genomic DNA. Translation: ADP91144.1.
HQ205550 Genomic DNA. Translation: ADP91147.1.
HQ205551 Genomic DNA. Translation: ADP91150.1.
HQ205552 Genomic DNA. Translation: ADP91153.1.
HQ205553 Genomic DNA. Translation: ADP91156.1.
HQ205554 Genomic DNA. Translation: ADP91159.1.
HQ205555 Genomic DNA. Translation: ADP91162.1.
HQ205556 Genomic DNA. Translation: ADP91165.1.
HQ205557 Genomic DNA. Translation: ADP91168.1.
HQ205558 Genomic DNA. Translation: ADP91171.1.
HQ205559 Genomic DNA. Translation: ADP91174.1.
HQ205560 Genomic DNA. Translation: ADP91177.1.
HQ205561 Genomic DNA. Translation: ADP91180.1.
HQ205562 Genomic DNA. Translation: ADP91183.1.
HQ205563 Genomic DNA. Translation: ADP91186.1.
HQ205564 Genomic DNA. Translation: ADP91189.1.
HQ205565 Genomic DNA. Translation: ADP91192.1.
HQ205566 Genomic DNA. Translation: ADP91195.1.
HQ205567 Genomic DNA. Translation: ADP91198.1.
HQ205568 Genomic DNA. Translation: ADP91201.1.
HQ205569 Genomic DNA. Translation: ADP91204.1.
HQ205570 Genomic DNA. Translation: ADP91207.1.
HQ205571 Genomic DNA. Translation: ADP91210.1.
HQ205572 Genomic DNA. Translation: ADP91213.1.
HQ205573 Genomic DNA. Translation: ADP91216.1.
HQ205574 Genomic DNA. Translation: ADP91219.1.
HQ205575 Genomic DNA. Translation: ADP91222.1.
HQ205576 Genomic DNA. Translation: ADP91225.1.
HQ205577 Genomic DNA. Translation: ADP91228.1.
HQ205578 Genomic DNA. Translation: ADP91231.1.
HQ205579 Genomic DNA. Translation: ADP91234.1.
HQ205580 Genomic DNA. Translation: ADP91237.1.
HQ205581 Genomic DNA. Translation: ADP91240.1.
HQ205582 Genomic DNA. Translation: ADP91243.1.
HQ205583 Genomic DNA. Translation: ADP91246.1.
HQ205584 Genomic DNA. Translation: ADP91249.1.
HQ205585 Genomic DNA. Translation: ADP91252.1.
AM183262 mRNA. Translation: CAJ65924.1.
HQ450643 mRNA. Translation: AED99114.1.
U01351 mRNA. Translation: AAA16603.1.
AK223594 mRNA. Translation: BAD97314.1.
BX640610 mRNA. Translation: CAE45716.1.
AY436590 Genomic DNA. Translation: AAQ97180.1.
EU332858 Genomic DNA. Translation: ABY87547.1.
AC005601 Genomic DNA. Translation: AAC34207.1.
AC004782 Genomic DNA. No translation available.
AC091925 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61872.1.
CH471062 Genomic DNA. Translation: EAW61873.1.
BC015610 mRNA. Translation: AAH15610.1.
M69104 Genomic DNA. Translation: AAA88049.1.
AH002750 Genomic DNA. Translation: AAA53151.1.
S68378 Genomic DNA. Translation: AAB20466.1.
CCDSiCCDS34258.1. [P04150-3]
CCDS4278.1. [P04150-1]
CCDS47298.1. [P04150-2]
PIRiA93370. QRHUGA.
B93370. QRHUGB.
RefSeqiNP_000167.1. NM_000176.2. [P04150-1]
NP_001018084.1. NM_001018074.1. [P04150-1]
NP_001018085.1. NM_001018075.1. [P04150-1]
NP_001018086.1. NM_001018076.1. [P04150-1]
NP_001018087.1. NM_001018077.1. [P04150-1]
NP_001018661.1. NM_001020825.1. [P04150-2]
NP_001019265.1. NM_001024094.1. [P04150-3]
NP_001191187.1. NM_001204258.1. [P04150-8]
NP_001191188.1. NM_001204259.1. [P04150-11]
NP_001191189.1. NM_001204260.1. [P04150-12]
NP_001191190.1. NM_001204261.1. [P04150-13]
NP_001191191.1. NM_001204262.1. [P04150-14]
NP_001191192.1. NM_001204263.1. [P04150-15]
NP_001191193.1. NM_001204264.1. [P04150-16]
XP_005268476.1. XM_005268419.3. [P04150-3]
XP_005268477.1. XM_005268420.4. [P04150-3]
XP_005268479.1. XM_005268422.3. [P04150-3]
XP_005268480.1. XM_005268423.3. [P04150-3]
UniGeneiHs.122926.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M2ZX-ray2.50A/D521-777[»]
1NHZX-ray2.30A500-777[»]
1P93X-ray2.70A/B/C/D500-777[»]
3BQDX-ray2.50A525-777[»]
3CLDX-ray2.84A/B521-777[»]
3E7CX-ray2.15A/B521-777[»]
3H52X-ray2.80A/B/C/D528-777[»]
3K22X-ray2.10A/B521-777[»]
3K23X-ray3.00A/B/C521-777[»]
4CSJX-ray2.30A500-777[»]
4HN5X-ray1.90A/B417-506[»]
4HN6X-ray2.55A/B417-506[»]
4LSJX-ray2.35A522-777[»]
4MDDX-ray2.40A/B522-777[»]
4P6WX-ray1.95A526-777[»]
4P6XX-ray2.50A/C/E/G/I/K523-777[»]
4UDCX-ray2.50A500-777[»]
4UDDX-ray1.80A500-777[»]
5CBXX-ray2.00A/B/E/F415-495[»]
5CBYX-ray2.00A/B415-495[»]
5CBZX-ray2.20A/B/E/F419-495[»]
5CC1X-ray2.30A/B/W/X417-506[»]
DisProtiDP00030.
ProteinModelPortaliP04150.
SMRiP04150. Positions 418-777.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109165. 161 interactions.
DIPiDIP-576N.
IntActiP04150. 73 interactions.
MINTiMINT-150603.
STRINGi9606.ENSP00000231509.

Chemistry

BindingDBiP04150.
ChEMBLiCHEMBL2034.
DrugBankiDB00240. Alclometasone.
DB00288. Amcinonide.
DB00394. Beclomethasone.
DB00443. Betamethasone.
DB01222. Budesonide.
DB01410. Ciclesonide.
DB01013. Clobetasol propionate.
DB00838. Clocortolone.
DB01380. Cortisone acetate.
DB01260. Desonide.
DB00547. Desoximetasone.
DB01234. Dexamethasone.
DB00223. Diflorasone.
DB06781. Difluprednate.
DB00687. Fludrocortisone.
DB00663. Flumethasone.
DB00180. Flunisolide.
DB00591. Fluocinolone Acetonide.
DB01047. Fluocinonide.
DB00324. Fluorometholone.
DB01185. Fluoxymesterone.
DB00846. Flurandrenolide.
DB08906. Fluticasone furoate.
DB00588. Fluticasone Propionate.
DB00596. Halobetasol Propionate.
DB00769. Hydrocortamate.
DB00741. Hydrocortisone.
DB00873. Loteprednol.
DB00253. Medrysone.
DB00351. Megestrol acetate.
DB00959. Methylprednisolone.
DB00834. Mifepristone.
DB00764. Mometasone.
DB01384. Paramethasone.
DB01130. Prednicarbate.
DB00860. Prednisolone.
DB00635. Prednisone.
DB00896. Rimexolone.
DB00421. Spironolactone.
DB00620. Triamcinolone.
DB08867. Ulipristal.
GuidetoPHARMACOLOGYi625.

PTM databases

iPTMnetiP04150.
PhosphoSiteiP04150.

Polymorphism and mutation databases

BioMutaiNR3C1.
DMDMi121069.

Proteomic databases

EPDiP04150.
MaxQBiP04150.
PaxDbiF5ATB7.
P04150.
PeptideAtlasiP04150.
PRIDEiP04150.

Protocols and materials databases

DNASUi2908.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000231509; ENSP00000231509; ENSG00000113580. [P04150-3]
ENST00000343796; ENSP00000343205; ENSG00000113580. [P04150-1]
ENST00000394464; ENSP00000377977; ENSG00000113580. [P04150-1]
ENST00000394466; ENSP00000377979; ENSG00000113580. [P04150-3]
ENST00000415690; ENSP00000387672; ENSG00000113580. [P04150-2]
ENST00000424646; ENSP00000405282; ENSG00000113580. [P04150-10]
ENST00000503201; ENSP00000427672; ENSG00000113580. [P04150-1]
ENST00000504572; ENSP00000422518; ENSG00000113580. [P04150-3]
GeneIDi2908.
KEGGihsa:2908.
UCSCiuc003lmy.4. human. [P04150-1]

Organism-specific databases

CTDi2908.
GeneCardsiNR3C1.
HGNCiHGNC:7978. NR3C1.
HPAiCAB010435.
HPA004248.
MalaCardsiNR3C1.
MIMi138040. gene.
615962. phenotype.
neXtProtiNX_P04150.
Orphaneti786. Glucocorticoid resistance.
PharmGKBiPA181.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3575. Eukaryota.
ENOG410XRZC. LUCA.
GeneTreeiENSGT00760000118887.
HOGENOMiHOG000037950.
HOVERGENiHBG007583.
InParanoidiP04150.
KOiK05771.
OMAiQSTFDIL.
PhylomeDBiP04150.
TreeFamiTF106510.

Enzyme and pathway databases

ReactomeiR-HSA-1368108. BMAL1:CLOCK,NPAS2 activates circadian gene expression.
R-HSA-383280. Nuclear Receptor transcription pathway.
R-HSA-8849473. PTK6 Expression.
SignaLinkiP04150.
SIGNORiP04150.

Miscellaneous databases

ChiTaRSiNR3C1. human.
EvolutionaryTraceiP04150.
GeneWikiiGlucocorticoid_receptor.
GenomeRNAii2908.
PROiP04150.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113580.
CleanExiHS_NR3C1.
ExpressionAtlasiP04150. baseline and differential.
GenevisibleiP04150. HS.

Family and domain databases

Gene3Di1.10.565.10. 1 hit.
3.30.50.10. 1 hit.
InterProiIPR001409. Glcrtcd_rcpt.
IPR000536. Nucl_hrmn_rcpt_lig-bd.
IPR001723. Nuclear_hrmn_rcpt.
IPR001628. Znf_hrmn_rcpt.
IPR013088. Znf_NHR/GATA.
[Graphical view]
PfamiPF02155. GCR. 1 hit.
PF00104. Hormone_recep. 1 hit.
PF00105. zf-C4. 1 hit.
[Graphical view]
PRINTSiPR00528. GLCORTICOIDR.
PR00398. STRDHORMONER.
PR00047. STROIDFINGER.
SMARTiSM00430. HOLI. 1 hit.
SM00399. ZnF_C4. 1 hit.
[Graphical view]
SUPFAMiSSF48508. SSF48508. 1 hit.
PROSITEiPS00031. NUCLEAR_REC_DBD_1. 1 hit.
PS51030. NUCLEAR_REC_DBD_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGCR_HUMAN
AccessioniPrimary (citable) accession number: P04150
Secondary accession number(s): A0ZXF9
, B0LPG8, D3DQF4, F5ATB7, P04151, Q53EP5, Q6N0A4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: September 7, 2016
This is version 230 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Isoform Beta: 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
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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.