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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)DescriptionActionsGraphical viewLength
DNA bindingi418 – 493Nuclear receptorPROSITE-ProRule annotationAdd BLAST76
Zinc fingeri421 – 441NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri457 – 476NR C4-typePROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

  • glucocorticoid-activated RNA polymerase II transcription factor binding transcription factor activity Source: UniProtKB
  • glucocorticoid receptor activity Source: ProtInc
  • protein complex binding Source: UniProtKB
  • 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

BioCyciZFISH:ENSG00000113580-MONOMER.
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
  • protein complex 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_075799423V → A in GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. 1 Publication1
Natural variantiVAR_013472477R → H in GCCR. 1 PublicationCorresponds to variant rs104893913dbSNPEnsembl.1
Natural variantiVAR_075800556T → 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 Publications1
Natural variantiVAR_015632559I → 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 rs104893909dbSNPEnsembl.1
Natural variantiVAR_075801575V → 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 Publication1
Natural variantiVAR_004676641D → V in GCCR. 1 PublicationCorresponds to variant rs104893908dbSNPEnsembl.1
Natural variantiVAR_013473679G → S in GCCR; has 50% binding affinity. 1 PublicationCorresponds to variant rs104893914dbSNPEnsembl.1
Natural variantiVAR_075802714R → Q in GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. 1 Publication1
Natural variantiVAR_075803726H → R in GCCR; unknown pathological significance; reduces transactivation and transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not impair DNA binding. 1 Publication1
Natural variantiVAR_004677729V → I in GCCR. 1 Publication1
Natural variantiVAR_071935737F → 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 rs121909727dbSNPEnsembl.1
Natural variantiVAR_015633747I → M in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. 1 PublicationCorresponds to variant rs104893910dbSNPEnsembl.1
Natural variantiVAR_071936773L → 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 rs104893912dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1M → T: Abolishes expression of A-type isoforms. 2 Publications1
Mutagenesisi27M → T: Abolishes expression of B-type isoforms. 2 Publications1
Mutagenesisi86M → I: Abolishes expression of C-type isoforms; when associated with I-90 and I-98. 1 Publication1
Mutagenesisi90M → I: Abolishes expression of C-type isoforms; when associated with I-86 and I-98. 1 Publication1
Mutagenesisi98M → I: Abolishes expression of C-type isoforms; when associated with I-86 and I-90. 1 Publication1
Mutagenesisi101D → A: Reduces transcription activation activity of isoform Alpha-C3 by half. 1 Publication1
Mutagenesisi101D → 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 Publication1
Mutagenesisi106 – 107QQ → LL: Reduces activity of isoform Alpha-C3 by half. 1 Publication2
Mutagenesisi113 – 114SS → AA: Does not affect the activity of isoform Alpha-C3. 1 Publication2
Mutagenesisi191F → D: Reduces transactivation by the ADA complex. 1 Publication1
Mutagenesisi193I → D: Reduces transactivation by the ADA complex. 1 Publication1
Mutagenesisi194L → A: Strongly reduces transactivation by the ADA complex; when associated with V-224 and F-225. 1 Publication1
Mutagenesisi197L → E: Reduces transactivation by the ADA complex. 1 Publication1
Mutagenesisi211S → A: Reduces expression of target genes IGFBP1 and IRF8. 1 Publication1
Mutagenesisi213W → A: Strongly reduces transactivation by the ADA complex. 1 Publication1
Mutagenesisi224L → V: Strongly reduces transactivation by the ADA complex; when associated with A-194 and F-225. 1 Publication1
Mutagenesisi225L → F: Strongly reduces transactivation by the ADA complex; when associated with A-194 and V-224. 1 Publication1
Mutagenesisi226S → A: Abolishes phosphorylation and enhances transcriptional activation. 1 Publication1
Mutagenesisi235F → L: Strongly reduces transactivation by the ADA complex; when associated with V-236. 1 Publication1
Mutagenesisi236L → V: Strongly reduces transactivation by the ADA complex; when associated with L-235. 1 Publication1
Mutagenesisi277K → R: Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-293. 1 Publication1
Mutagenesisi293K → R: Strongly reduces sumoylation. Almost complete loss of sumoylation; when associated with R-277. 1 Publication1
Mutagenesisi316M → I: Abolishes expression of D-type isoforms; when associated with I-331 and I-336. 1 Publication1
Mutagenesisi331M → I: Abolishes expression of D-type isoforms; when associated with I-316 and I-336. 1 Publication1
Mutagenesisi336M → I: Abolishes expression of D-type isoforms; when associated with I-316 and I-331. 1 Publication1
Mutagenesisi404S → 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 Publication1
Mutagenesisi404S → D: Does not affect translocation to the nucleus following ligand stimulation. 1 Publication1
Mutagenesisi480K → 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 Publication1
Mutagenesisi492K → 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 Publication1
Mutagenesisi494K → 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 Publication1
Mutagenesisi495K → 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 Publication1
Mutagenesisi585R → A: Reduces activation mediated by ligand binding domain; when associated with A-590. 1 Publication1
Mutagenesisi590D → A: Reduces activation mediated by ligand binding domain; when associated with A-585. 1 Publication1
Mutagenesisi602F → S: Increases solubility. No effect on transactivation by dexamethasone. 1 Publication1
Mutagenesisi625P → A: Decreases transactivation by dexamethasone by 95%. 1 Publication1
Mutagenesisi628I → A: Decreases dimerization and transactivation by dexamethasone; when associated with S-602. 1 Publication1
Mutagenesisi703K → R: Slightly reduces sumoylation. Inhibits the stimulatory effect of RWDD3 on its transcriptional activity. 2 Publications1

Keywords - Diseasei

Disease mutation, Pseudohermaphroditism

Organism-specific databases

DisGeNETi2908.
MalaCardsiNR3C1.
MIMi615962. phenotype.
OpenTargetsiENSG00000113580.
Orphaneti786. Glucocorticoid resistance.
PharmGKBiPA181.

Chemistry databases

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)DescriptionActionsGraphical viewLength
ChainiPRO_00000199371 – 777Glucocorticoid receptorAdd BLAST777

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei8PhosphothreonineCombined sources1
Modified residuei23Omega-N-methylarginineBy similarity1
Modified residuei45PhosphoserineCombined sources1
Modified residuei113PhosphoserineBy similarity1
Modified residuei134PhosphoserineCombined sources1
Modified residuei141PhosphoserineBy similarity1
Modified residuei203PhosphoserineCombined sources3 Publications1
Modified residuei211Phosphoserine3 Publications1
Modified residuei226PhosphoserineCombined sources1 Publication1
Modified residuei267PhosphoserineCombined sources1
Cross-linki277Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Cross-linki293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate1 Publication
Cross-linki293Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei404Phosphoserine; by GSK3-beta1 Publication1
Modified residuei480N6-acetyllysine1 Publication1
Modified residuei492N6-acetyllysine1 Publication1
Modified residuei494N6-acetyllysine1 Publication1
Modified residuei495N6-acetyllysine1 Publication1
Cross-linki703Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Isoform Alpha-B (identifier: P04150-8)
Modified residuei1N-acetylmethionineCombined sources1
Isoform Beta-B (identifier: P04150-9)
Modified residuei1N-acetylmethionineCombined sources1 Publication1

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 conjugation

Proteomic databases

EPDiP04150.
PaxDbiF5ATB7.
P04150.
PeptideAtlasiP04150.
PRIDEiP04150.

PTM databases

iPTMnetiP04150.
PhosphoSitePlusiP04150.

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). Interacts with FNIP1 and FNIP2 (PubMed:27353360).By similarity20 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

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP04150.

Structurei

Secondary structure

1777
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni422 – 424Combined sources3
Beta strandi430 – 432Combined sources3
Beta strandi435 – 437Combined sources3
Helixi439 – 449Combined sources11
Beta strandi458 – 461Combined sources4
Turni467 – 472Combined sources6
Helixi474 – 484Combined sources11
Turni525 – 527Combined sources3
Helixi532 – 538Combined sources7
Beta strandi550 – 552Combined sources3
Helixi556 – 579Combined sources24
Helixi584 – 586Combined sources3
Helixi589 – 615Combined sources27
Beta strandi617 – 619Combined sources3
Beta strandi621 – 624Combined sources4
Beta strandi627 – 629Combined sources3
Helixi631 – 634Combined sources4
Helixi639 – 655Combined sources17
Helixi660 – 671Combined sources12
Beta strandi673 – 675Combined sources3
Helixi683 – 702Combined sources20
Beta strandi704 – 706Combined sources3
Helixi708 – 741Combined sources34
Helixi743 – 745Combined sources3
Helixi751 – 765Combined sources15
Beta strandi769 – 771Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5EMCX-ray2.30A/B411-500[»]
5EMPX-ray2.30A/B411-500[»]
5EMQX-ray2.30A/B411-500[»]
DisProtiDP00030.
ProteinModelPortaliP04150.
SMRiP04150.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04150.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 420ModulatingAdd BLAST420
Regioni98 – 115Required for high transcriptional activity of isoform Alpha-C31 PublicationAdd BLAST18
Regioni485 – 777Interaction with CLOCKAdd BLAST293
Regioni487 – 527HingeAdd BLAST41
Regioni528 – 777Steroid-bindingAdd BLAST250
Regioni532 – 697Interaction with CRY11 PublicationAdd BLAST166

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi399 – 418Glu/Pro/Ser/Thr-rich (PEST region)Add BLAST20

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)DescriptionActionsGraphical viewLength
Zinc fingeri421 – 441NR C4-typePROSITE-ProRule annotationAdd BLAST21
Zinc fingeri457 – 476NR C4-typePROSITE-ProRule annotationAdd BLAST20

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)DescriptionActionsGraphical viewLength
Sequence conflicti399R → G in BAD97314 (Ref. 7) Curated1
Sequence conflicti754A → T in BAD97314 (Ref. 7) Curated1

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_01414023R → K Polymorphism; reduces transactivation activity; does not affect transrepression activity. 8 PublicationsCorresponds to variant rs6190dbSNPEnsembl.1
Natural variantiVAR_01562829F → L.1 PublicationCorresponds to variant rs148102613dbSNPEnsembl.1
Natural variantiVAR_01462265F → V.2 PublicationsCorresponds to variant rs6192dbSNPEnsembl.1
Natural variantiVAR_07579772N → D Polymorphism; associated in cis with A-321 and S-766 in one individual; doubles transactivation potential. 1 Publication1
Natural variantiVAR_015629112L → F.1 PublicationCorresponds to variant rs542110718dbSNPEnsembl.1
Natural variantiVAR_015630233D → N.1 Publication1
Natural variantiVAR_075798321V → A Polymorphism; associated in cis with D-72 and S-766 in one individual; doubles transactivation potential. 1 Publication1
Natural variantiVAR_004675363N → 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 rs6195dbSNPEnsembl.1
Natural variantiVAR_015631421C → Y in a glucocorticoid resistant leukemia cell line. 1 Publication1
Natural variantiVAR_075799423V → A in GCCR; unknown pathological significance; reduces transactivation activity; delays nuclear translocation; does not exert a dominant negative effect; impairs DNA binding. 1 Publication1
Natural variantiVAR_013472477R → H in GCCR. 1 PublicationCorresponds to variant rs104893913dbSNPEnsembl.1
Natural variantiVAR_075800556T → 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 Publications1
Natural variantiVAR_015632559I → 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 rs104893909dbSNPEnsembl.1
Natural variantiVAR_025014571V → 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 rs104893911dbSNPEnsembl.1
Natural variantiVAR_075801575V → 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 Publication1
Natural variantiVAR_004676641D → V in GCCR. 1 PublicationCorresponds to variant rs104893908dbSNPEnsembl.1
Natural variantiVAR_013473679G → S in GCCR; has 50% binding affinity. 1 PublicationCorresponds to variant rs104893914dbSNPEnsembl.1
Natural variantiVAR_075802714R → Q in GCCR; unknown pathological significance; reduces transactivation; reduces affinity for ligand; exerts a dominant negative effect; does not impair DNA binding. 1 Publication1
Natural variantiVAR_075803726H → R in GCCR; unknown pathological significance; reduces transactivation and transrepression activity; reduces affinity for ligand; delays nuclear translocation; does not impair DNA binding. 1 Publication1
Natural variantiVAR_004677729V → I in GCCR. 1 Publication1
Natural variantiVAR_071935737F → 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 rs121909727dbSNPEnsembl.1
Natural variantiVAR_015633747I → M in GCCR; alters interaction with NCOA2 and strongly reduces transcription activation; acts as dominant negative mutant. 1 PublicationCorresponds to variant rs104893910dbSNPEnsembl.1
Natural variantiVAR_004678753L → F in two glucocorticoid resistant leukemia cell lines lacking the normal allele. 2 PublicationsCorresponds to variant rs121909726dbSNPEnsembl.1
Natural variantiVAR_075804766N → S Polymorphism; associated in cis with D-72 and A-321 in one individual; doubles transactivation potential. 1 Publication1
Natural variantiVAR_071936773L → 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 rs104893912dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0583121 – 335Missing in isoform Alpha-D3. 1 PublicationAdd BLAST335
Alternative sequenceiVSP_0583131 – 330Missing in isoform Alpha-D2. 1 PublicationAdd BLAST330
Alternative sequenceiVSP_0583141 – 315Missing in isoform Alpha-D1. 1 PublicationAdd BLAST315
Alternative sequenceiVSP_0583151 – 97Missing in isoform Alpha-C3. 1 PublicationAdd BLAST97
Alternative sequenceiVSP_0583161 – 89Missing in isoform Alpha-C2. 1 PublicationAdd BLAST89
Alternative sequenceiVSP_0583171 – 85Missing in isoform Alpha-C1. 1 PublicationAdd BLAST85
Alternative sequenceiVSP_0187731 – 26Missing in isoform Alpha-B and isoform Beta-B. CuratedAdd BLAST26
Alternative sequenceiVSP_043908313 – 338Missing in isoform 10. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_007363451G → GR in isoform Alpha-2 and isoform Beta-2. 1 Publication1
Alternative sequenceiVSP_013340491 – 674Missing in isoform GR-A alpha and isoform GR-A beta. CuratedAdd BLAST184
Alternative sequenceiVSP_003703728 – 777VVENL…LFHQK → NVMWLKPESTSHTLI in isoform Beta, isoform Beta-B, isoform Beta-2 and isoform GR-A beta. 1 PublicationAdd BLAST50

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]
XP_016864886.1. XM_017009397.1. [P04150-1]
XP_016864887.1. XM_017009398.1. [P04150-1]
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]
XP_016864886.1. XM_017009397.1. [P04150-1]
XP_016864887.1. XM_017009398.1. [P04150-1]
UniGeneiHs.122926.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5EMCX-ray2.30A/B411-500[»]
5EMPX-ray2.30A/B411-500[»]
5EMQX-ray2.30A/B411-500[»]
DisProtiDP00030.
ProteinModelPortaliP04150.
SMRiP04150.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

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.
PhosphoSitePlusiP04150.

Polymorphism and mutation databases

BioMutaiNR3C1.
DMDMi121069.

Proteomic databases

EPDiP04150.
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.
DisGeNETi2908.
GeneCardsiNR3C1.
HGNCiHGNC:7978. NR3C1.
HPAiCAB010435.
HPA004248.
MalaCardsiNR3C1.
MIMi138040. gene.
615962. phenotype.
neXtProtiNX_P04150.
OpenTargetsiENSG00000113580.
Orphaneti786. Glucocorticoid resistance.
PharmGKBiPA181.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113580-MONOMER.
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: November 30, 2016
This is version 233 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.