Glucocorticoid receptor

UniProt P04150 Organism Homo sapiens Gene GRL, NR3C1

Also known as: GRL, NR3C1

Function

Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth (By similarity).

Classification

Family (Pfam): PF02155 GCR, PF00104 Hormone_recep, PF00105 zf-C4
InterPro: Glcrtcd_rcpt, NHR-like_dom_sf, Nucl_hrmn_rcpt_lig-bd, Nuclear_hormone_rcpt_NR3, Nuclear_hrmn_rcpt, Znf_hrmn_rcpt, Znf_NHR/GATA
Functional cluster: Homeobox & Zinc-Finger Transcription Factors

Experimental structures · PDB · 58

1M2Z X-ray 2.50A
1NHZ X-ray 2.30A
1P93 X-ray 2.70A
3BQD X-ray 2.50A
3CLD X-ray 2.84A
3E7C X-ray 2.15A
3H52 X-ray 2.80A
3K22 X-ray 2.10A
3K23 X-ray 3.00A
4CSJ X-ray 2.30A
4HN5 X-ray 1.90A
4HN6 X-ray 2.55A
… and 46 more

A predicted model is available from AlphaFold.

Gene Ontology · 55

Disease associations

glucocorticoid resistance MONDO:0014421

Drugs targeting this protein · 74

HYDROCORTISONE ACETATE agonist
PREDNISOLONE ACETATE agonist
CLOBETASOL PROPIONATE agonist
MOMETASONE FUROATE agonist
PARAMETHASONE ACETATE agonist
BETAMETHASONE BENZOATE agonist
BETAMETHASONE DIPROPIONATE agonist
PREDNICARBATE agonist
TRIAMCINOLONE DIACETATE agonist
HYDROCORTISONE SODIUM SUCCINATE agonist
BECLOMETHASONE DIPROPIONATE agonist
BETAMETHASONE ACETATE agonist
DIFLORASONE DIACETATE agonist
HYDROCORTISONE VALERATE agonist
FLUOROMETHOLONE agonist
RIMEXOLONE agonist
HYDROCORTAMATE HYDROCHLORIDE agonist
AMCINONIDE agonist
BETAMETHASONE SODIUM PHOSPHATE agonist
FLUPREDNISOLONE agonist
HALCINONIDE agonist
LOTEPREDNOL ETABONATE agonist
FLUMETHASONE PIVALATE agonist
TRIAMCINOLONE HEXACETONIDE agonist
HALOBETASOL PROPIONATE agonist
PREDNISOLONE TEBUTATE agonist
HYDROCORTISONE PROBUTATE agonist
HYDROCORTISONE SODIUM PHOSPHATE agonist
CLOCORTOLONE PIVALATE agonist
ALCLOMETASONE DIPROPIONATE agonist
FLURANDRENOLIDE agonist
PREDNISOLONE SODIUM PHOSPHATE agonist
FLUOROMETHOLONE ACETATE agonist
METHYLPREDNISOLONE SODIUM SUCCINATE agonist
DESONIDE agonist
MEPREDNISONE agonist
MEDRYSONE agonist
DIFLUPREDNATE agonist
DEFLAZACORT agonist
MIFEPRISTONE antagonist
PREDNISOLONE agonist
METHYLPREDNISOLONE ACETATE agonist
BUDESONIDE agonist
CYPROTERONE ACETATE antagonist
TRIAMCINOLONE agonist
FLUTICASONE PROPIONATE agonist
BETAMETHASONE VALERATE agonist
FLUOCINONIDE agonist
TRIAMCINOLONE ACETONIDE agonist
FLUNISOLIDE agonist
DEXAMETHASONE ACETATE agonist
HYDROCORTISONE CYPIONATE agonist
CORTISONE ACETATE agonist
FLUTICASONE FUROATE agonist
HYDROCORTISONE BUTYRATE agonist
DESOXIMETASONE agonist
DEXAMETHASONE SODIUM PHOSPHATE agonist
CICLESONIDE agonist
MAPRACORAT agonist
CORTIVAZOL agonist
VAMOROLONE agonist
CORT 108297 antagonist
DAGROCORAT modulator
FOSDAGROCORAT modulator
ORG-34517 antagonist
VELSECORAT modulator
DEXAMETHASONE agonist
HYDROCORTISONE agonist
RELACORILANT antagonist
AZD-5423 modulator
BETAMETHASONE agonist
PREDNISONE agonist
METHYLPREDNISOLONE agonist
FLUOCINOLONE ACETONIDE agonist

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Zinc finger protein 764 1 shared papers
Glucocorticoid receptor 5 shared papers
Nuclear receptor subfamily 4 group A member 3 1 shared papers
Proline-rich nuclear receptor coactivator 2 1 shared papers
Glucocorticoid receptor 4 shared papers
Transcriptional adapter 2-alpha 1 shared papers
Protein HEXIM1 1 shared papers
Germinal-center associated nuclear protein 1 shared papers
BAG family molecular chaperone regulator 1 1 shared papers
Protein unc-45 homolog A 1 shared papers
Transforming growth factor beta-1-induced transcript 1 protein 1 shared papers
Heterogeneous nuclear ribonucleoprotein U 1 shared papers

Literature · 98 cited papers

UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability. Mol. Cell · 2023
ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development. Nucleic Acids Res. · 2019
Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding of kinase and non-kinase clients. EMBO J. · 2017
Genome-wide Regulatory Roles of the C2H2-type Zinc Finger Protein ZNF764 on the Glucocorticoid Receptor. Sci. Rep. · 2017
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance drug binding. Nat. Commun. · 2016
Three novel heterozygous point mutations of NR3C1 causing glucocorticoid resistance. Hum. Mutat. · 2016
Human Glucocorticoid Receptor beta (hGRbeta) Regulates Gluconeogenesis and Inflammation in Mouse Liver. Mol. Cell. Biol. · 2015
Functional characterization of the hGRalphaT556I causing Chrousos syndrome. Eur. J. Clin. Invest. · 2016
A novel mutation of the hGR gene causing Chrousos syndrome. Eur. J. Clin. Invest. · 2015
Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy. Proc. Natl. Acad. Sci. U.S.A. · 2015
Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner to recruit UPF1 for rapid mRNA degradation. Proc. Natl. Acad. Sci. U.S.A. · 2015
… and 86 more in the literature graph

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