ID GCR_RAT Reviewed; 795 AA. AC P06536; O08624; Q8R463; Q8R5J0; DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 30-AUG-2017, entry version 202. DE RecName: Full=Glucocorticoid receptor; DE Short=GR; DE AltName: Full=Nuclear receptor subfamily 3 group C member 1; GN Name=Nr3c1; Synonyms=Grl; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Hepatoma; RX PubMed=3755378; DOI=10.1016/0092-8674(86)90659-8; RA Miesfeld R., Rusconi S., Godowski P.J., Maler B.A., Okret S., RA Wikstroem A.-C., Gustafsson J.-A., Yamamoto K.R.; RT "Genetic complementation of a glucocorticoid receptor deficiency by RT expression of cloned receptor cDNA."; RL Cell 46:389-399(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Heeley R.P., Gill E., van Zutphen B.; RT "CAG repeat variation in the gene for rat glucocorticoid receptor: a RT study of allele frequencies in inbred and wild rat populations and of RT the steroid-binding properties of their polypeptides in vitro."; RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLY-226 AND ASP-260. RC STRAIN=Brown Norway/Crl, and SHR/OlaIpcv; RA Pravenec M., Zidek V., Kostka V., Mlejnek P., Musilova A., Kren V., RA Jansa P., Forejt J., Lezin E.S., Kurtz T.W.; RT "Genetic isolation of a QTL on chromosome 18 associated with salt RT sensitivity in spontaneously hypertensive rats."; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-515. RC STRAIN=Sprague-Dawley; TISSUE=Prostate; RX PubMed=3684608; DOI=10.1093/nar/15.22.9603; RA Chang C., Kokontis J., Chang C.T., Liao S.; RT "Cloning and sequence analysis of the rat ventral prostate RT glucocorticoid receptor cDNA."; RL Nucleic Acids Res. 15:9603-9603(1987). RN [5] RP MUTAGENESIS OF ZINC-FINGER. RX PubMed=3191912; RA Severne Y., Wieland S., Schaffner W., Rusconi S.; RT "Metal binding 'finger' structures in the glucocorticoid receptor RT defined by site-directed mutagenesis."; RL EMBO J. 7:2503-2508(1988). RN [6] RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION. RX PubMed=3216865; DOI=10.1210/mend-2-12-1256; RA Dong Y., Poellinger L., Gustafsson J.-A., Okret S.; RT "Regulation of glucocorticoid receptor expression: evidence for RT transcriptional and posttranslational mechanisms."; RL Mol. Endocrinol. 2:1256-1264(1988). RN [7] RP MUTAGENESIS OF CYS-656. RX PubMed=1939229; RA Chakraborti P.K., Garabedian M.J., Yamamoto K.R., Simons S.S. Jr.; RT "Creation of 'super' glucocorticoid receptors by point mutations in RT the steroid binding domain."; RL J. Biol. Chem. 266:22075-22078(1991). RN [8] RP MUTAGENESIS OF ZINC-FINGER. RX PubMed=8450530; DOI=10.1006/jmbi.1993.1130; RA Zandi E., Galli I., Doebbeling U., Rusconi S.; RT "Zinc finger mutations that alter domain interactions in the RT glucocorticoid receptor."; RL J. Mol. Biol. 230:124-136(1993). RN [9] RP REVIEW ON MUTAGENESIS. RX PubMed=8191545; DOI=10.1016/0039-128X(94)90093-0; RA Lanz R.B., Hug M., Gola M., Tallone T., Wieland S., Rusconi S.; RT "Active, interactive, and inactive steroid receptor mutants."; RL Steroids 59:148-152(1994). RN [10] RP HOMODIMERIZATION, HETERODIMERIZATION WITH NR3C2, AND MUTAGENESIS OF RP ASP-481. RX PubMed=8618925; DOI=10.1073/pnas.92.26.12480; RA Liu W., Wang J., Sauter N.K., Pearce D.; RT "Steroid receptor heterodimerization demonstrated in vitro and in RT vivo."; RL Proc. Natl. Acad. Sci. U.S.A. 92:12480-12484(1995). RN [11] RP INTERACTION WITH NCOA2. RX PubMed=9111344; DOI=10.1128/MCB.17.5.2735; RA Hong H., Kohli K., Garabedian M.J., Stallcup M.R.; RT "GRIP1, a transcriptional coactivator for the AF-2 transactivation RT domain of steroid, thyroid, retinoid, and vitamin D receptors."; RL Mol. Cell. Biol. 17:2735-2744(1997). RN [12] RP PHOSPHORYLATION AT THR-171; SER-224; SER-232 AND SER-246. RX PubMed=9603939; DOI=10.1074/jbc.273.23.14315; RA Rogatsky I., Waase C.L.M., Garabedian M.J.; RT "Phosphorylation and inhibition of rat glucocorticoid receptor RT transcriptional activation by glycogen synthase kinase-3 (GSK-3). RT Species-specific differences between human and rat glucocorticoid RT receptor signaling as revealed through GSK-3 phosphorylation."; RL J. Biol. Chem. 273:14315-14321(1998). RN [13] RP INTERACTION WITH NRIP1. RX PubMed=10364267; DOI=10.1074/jbc.274.25.18121; RA Subramaniam N., Treuter E., Okret S.; RT "Receptor interacting protein RIP140 inhibits both positive and RT negative gene regulation by glucocorticoids."; RL J. Biol. Chem. 274:18121-18127(1999). RN [14] RP INTERACTION WITH POU2F1 AND POU2F2, AND MUTAGENESIS OF CYS-500 AND RP LEU-501. RX PubMed=10480874; DOI=10.1074/jbc.274.38.26713; RA Prefontaine G.G., Walther R., Giffin W., Lemieux M.E., Pope L., RA Hache R.J.G.; RT "Selective binding of steroid hormone receptors to octamer RT transcription factors determines transcriptional synergism at the RT mouse mammary tumor virus promoter."; RL J. Biol. Chem. 274:26713-26719(1999). RN [15] RP INTERACTION WITH NCOA6. RX PubMed=10866662; DOI=10.1128/MCB.20.14.5048-5063.2000; RA Mahajan M.A., Samuels H.H.; RT "A new family of nuclear receptor coregulators that integrates nuclear RT receptor signaling through CBP."; RL Mol. Cell. Biol. 20:5048-5063(2000). RN [16] RP HOMODIMERIZATION, HETERODIMERIZATION WITH NR3C2, AND MUTAGENESIS OF RP LEU-501. RX PubMed=11278286; DOI=10.1074/jbc.M005363200; RA Ou X.-M., Storring J.M., Kushwaha N., Albert P.R.; RT "Heterodimerization of mineralocorticoid and glucocorticoid receptors RT at a novel negative response element of the 5-HT1A receptor gene."; RL J. Biol. Chem. 276:14299-14307(2001). RN [17] RP ALTERNATIVE INITIATION, AND MUTAGENESIS OF MET-1 AND MET-28. RX PubMed=11435610; DOI=10.1210/mend.15.7.0667; RA Yudt M.R., Cidlowski J.A.; RT "Molecular identification and characterization of A and B forms of the RT glucocorticoid receptor."; RL Mol. Endocrinol. 15:1093-1103(2001). RN [18] RP INTERACTION WITH NCOA1, AND MUTAGENESIS OF GLU-773. RX PubMed=12118039; DOI=10.1074/jbc.M204013200; RA Kucera T., Waltner-Law M., Scott D.K., Prasad R., Granner D.K.; RT "A point mutation of the AF2 transactivation domain of the RT glucocorticoid receptor disrupts its interaction with steroid receptor RT coactivator 1."; RL J. Biol. Chem. 277:26098-26102(2002). RN [19] RP FUNCTION, INTERACTION WITH NCOA1; NCOA3; SMARCA4; SMARCC1; SMARCD1 AND RP SMARCE1, AND MUTAGENESIS OF ARG-488. RX PubMed=12917342; DOI=10.1128/MCB.23.17.6210-6220.2003; RA Hsiao P.W., Fryer C.J., Trotter K.W., Wang W., Archer T.K.; RT "BAF60a mediates critical interactions between nuclear receptors and RT the BRG1 chromatin-remodeling complex for transactivation."; RL Mol. Cell. Biol. 23:6210-6220(2003). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=16641100; DOI=10.1073/pnas.0600895103; RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.; RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells: RT regulation of aquaporin-2 phosphorylation at two sites."; RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006). RN [21] RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=21730050; DOI=10.1074/jbc.M111.256610; RA Gallo L.I., Lagadari M., Piwien-Pilipuk G., Galigniana M.D.; RT "The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is RT a mitochondrial protein that translocates to the nucleus to protect RT cells against oxidative stress."; RL J. Biol. Chem. 286:30152-30160(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-224; SER-232 AND RP SER-287, VARIANT [LARGE SCALE ANALYSIS] GLY-226, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., RA Lundby C., Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 RT different rat organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [23] RP SUMOYLATION AT LYS-297; LYS-313 AND LYS-721, INTERACTION WITH RP UBE2I/UBC9 AND RWDD3, AND MUTAGENESIS OF LYS-297; LYS-313 AND LYS-721. RX PubMed=23508108; DOI=10.1128/MCB.01470-12; RA Druker J., Liberman A.C., Antunica-Noguerol M., Gerez J., RA Paez-Pereda M., Rein T., Iniguez-Lluhi J.A., Holsboer F., Arzt E.; RT "RSUME enhances glucocorticoid receptor SUMOylation and RT transcriptional activity."; RL Mol. Cell. Biol. 33:2116-2127(2013). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 434-525. RX PubMed=1865905; DOI=10.1038/352497a0; RA Luisi B.F., Xu W.X., Otwinowski Z., Freedman L.P., Yamamoto K.R., RA Sigler P.B.; RT "Crystallographic analysis of the interaction of the glucocorticoid RT receptor with DNA."; RL Nature 352:497-505(1991). RN [25] RP STRUCTURE BY NMR OF 440-510. RX PubMed=2115209; DOI=10.1126/science.2115209; RA Haerd T., Kellenbach E., Boelens R., Maler B.A., Dahlman K., RA Freedman L.P., Carlstedt-Duke J., Yamamoto K.R., Gustafsson J.-A., RA Kaptein R.; RT "Solution structure of the glucocorticoid receptor DNA-binding RT domain."; RL Science 249:157-160(1990). RN [26] RP STRUCTURE BY NMR OF 440-525. RX PubMed=1751485; DOI=10.1021/bi00114a003; RA Remerowski M.L., Kellenbach E., Boelens R., van der Marel A., RA van Boom J.H., Maler B.A., Yamamoto K.R., Kaptein R.; RT "1H NMR studies of DNA recognition by the glucocorticoid receptor: RT complex of the DNA binding domain with a half-site response element."; RL Biochemistry 30:11620-11624(1991). RN [27] RP STRUCTURE BY NMR OF 440-525. RX PubMed=1936288; DOI=10.1016/0014-5793(91)81322-Y; RA Kellenbach E., Maler B.A., Yamamoto K.R., Boelens R., Kaptein R.; RT "Identification of the metal coordinating residues in the DNA binding RT domain of the glucocorticoid receptor by 113Cd-1H heteronuclear NMR RT spectroscopy."; RL FEBS Lett. 291:367-370(1991). RN [28] RP STRUCTURE BY NMR OF 439-510. RX PubMed=8257681; DOI=10.1021/bi00212a011; RA Baumann H., Paulsen K., Kovacs H., Berglund H., Wright A.P.H., RA Gustafsson J.-A., Haerd T.; RT "Refined solution structure of the glucocorticoid receptor DNA-binding RT domain."; RL Biochemistry 32:13463-13471(1993). RN [29] RP POLYMORPHISM OF POLY-GLN REGION. RX PubMed=8493115; DOI=10.1093/nar/21.8.2014; RA Gearing K.L., Gustafsson J.-A., Okret S.; RT "Heterogeneity in the polyglutamine tract of the glucocorticoid RT receptor from different rat strains."; RL Nucleic Acids Res. 21:2014-2014(1993). CC -!- FUNCTION: Receptor for glucocorticoids (GC). Has a dual mode of CC action: as a transcription factor that binds to glucocorticoid CC response elements (GRE), both for nuclear and mitochondrial DNA, CC and as a modulator of other transcription factors. Affects CC inflammatory responses, cellular proliferation and differentiation CC in target tissues. Involved in chromatin remodeling CC (PubMed:12917342). Plays a role in rapid mRNA degradation by CC binding to the 5' UTR of target mRNAs and interacting with PNRC2 CC in a ligand-dependent manner which recruits the RNA helicase UPF1 CC and the mRNA-decapping enzyme DCP1A, leading to RNA decay (By CC similarity). Could act as a coactivator for STAT5-dependent CC transcription upon growth hormone (GH) stimulation and could CC reveal an essential role of hepatic GR in the control of body CC growth (By similarity). {ECO:0000250|UniProtKB:P04150, CC ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:12917342}. CC -!- FUNCTION: Isoform A: Has transcriptional activation and repression CC activity. Mediates glucocorticoid-induced apoptosis. Promotes CC accurate chromosome segregation during mitosis. May act as a tumor CC suppressor. May play a negative role in adipogenesis through the CC regulation of lipolytic and antilipogenic gene expression. CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537}. CC -!- SUBUNIT: Interacts with GRIP1 (By similarity). Heteromultimeric CC cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or CC another immunophilin such as PPID, STIP1, or the immunophilin CC homolog PPP5C (PubMed:21730050). Upon ligand binding FKBP5 CC dissociates from the complex and FKBP4 takes its place, thereby CC linking the complex to dynein and mediating transport to the CC nucleus, where the complex dissociates (By similarity). Directly CC interacts with UNC45A (By similarity). Binds to DNA as a CC homodimer, and as heterodimer with NR3C2 or the retinoid X CC receptor (By similarity). Binds STAT5A and STAT5B homodimers and CC heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 CC and TRIM28 (PubMed:10364267, PubMed:10480874). Interacts with CC several coactivator complexes, including the SMARCA4 complex, CC CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as CC NCOA2 and NCOA6 (PubMed:9111344, PubMed:10866662). Interaction CC with BAG1 inhibits transactivation (By similarity). Interacts with CC HEXIM1, PELP1 and TGFB1I1 (By similarity). Interacts with NCOA1 CC (PubMed:12917342). Interacts with NCOA3, SMARCA4, SMARCC1, CC SMARCD1, and SMARCE1 (PubMed:12917342, PubMed:12118039). Interacts CC with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (By CC similarity). Interacts with CIART (By similarity). Interacts with CC RWDD3 (PubMed:23508108). Interacts with UBE2I/UBC9 and this CC interaction is enhanced in the presence of RWDD3 CC (PubMed:23508108). Interacts with NR4A3 (via nuclear receptor DNA- CC binding domain), represses transcription activity of NR4A3 on the CC POMC promoter Nur response element (NurRE) (By similarity). CC Directly interacts with PNRC2 to attract and form a complex with CC UPF1 and DCP1A; the interaction leads to rapid mRNA degradation CC (By similarity). Interacts with GSK3B (By similarity). Interacts CC with FNIP1 and FNIP2 (By similarity). CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:10364267, ECO:0000269|PubMed:10480874, CC ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:12118039, CC ECO:0000269|PubMed:12917342, ECO:0000269|PubMed:21730050, CC ECO:0000269|PubMed:23508108, ECO:0000269|PubMed:9111344}. CC -!- INTERACTION: CC Q62667:Mvp; NbExp=2; IntAct=EBI-1187143, EBI-918333; CC Q15788:NCOA1 (xeno); NbExp=2; IntAct=EBI-1187143, EBI-455189; CC Q9BTK6:PAGR1 (xeno); NbExp=2; IntAct=EBI-1187143, EBI-2372223; CC P51532:SMARCA4 (xeno); NbExp=3; IntAct=EBI-1187143, EBI-302489; CC Q96GM5:SMARCD1 (xeno); NbExp=2; IntAct=EBI-1187143, EBI-358489; CC -!- SUBCELLULAR LOCATION: Isoform A: Cytoplasm CC {ECO:0000250|UniProtKB:P04150}. Nucleus CC {ECO:0000250|UniProtKB:P04150}. Mitochondrion CC {ECO:0000269|PubMed:21730050}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000250|UniProtKB:P04150}. Cytoplasm, cytoskeleton, CC microtubule organizing center, centrosome CC {ECO:0000250|UniProtKB:P04150}. Note=After ligand activation, CC translocates from the cytoplasm to the nucleus. CC {ECO:0000250|UniProtKB:P04150}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=A; CC IsoId=P06536-1; Sequence=Displayed; CC Name=B; CC IsoId=P06536-2; Sequence=VSP_018969; CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, CC a DNA-binding domain and a C-terminal ligand-binding domain. The CC ligand-binding domain is required for correct chromosome CC segregation during mitosis although ligand binding is not CC required. {ECO:0000250|UniProtKB:P04150}. CC -!- PTM: Acetylation by CLOCK reduces its binding to glucocorticoid CC response elements and its transcriptional activity. {ECO:0000250}. CC -!- PTM: Increased proteasome-mediated degradation in response to CC glucocorticoids. {ECO:0000250|UniProtKB:P04150}. CC -!- PTM: Phosphorylated in the absence of hormone; becomes CC hyperphosphorylated in the presence of glucocorticoids. The Ser- CC 224, Ser-246 and Ser-424-phosphorylated forms are mainly CC cytoplasmic, and the Ser-232-phosphorylated form is nuclear. CC Phosphorylation at Ser-232 increases transcriptional activity. CC Phosphorylation at Ser-224, Ser-246 and Ser-424 decreases CC signaling capacity. Phosphorylation at Ser-424 may protect from CC glucocorticoid-induced apoptosis. Phosphorylation at Ser-224 and CC Ser-232 is not required in regulation of chromosome segregation. CC May be dephosphorylated by PPP5C, attenuates NR3C1 action. CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06537}. CC -!- PTM: Sumoylation at Lys-297 and Lys-313 negatively regulates its CC transcriptional activity. Sumoylation at Lys-721 positively CC regulates its transcriptional activity in the presence of RWDD3. CC Sumoylation at Lys-297 and Lys-313 is dispensable whereas CC sumoylation at Lys-721 is critical for the stimulatory effect of CC RWDD3 on its transcriptional activity. Heat shock increases CC sumoylation in a RWDD3-dependent manner. CC {ECO:0000269|PubMed:23508108}. CC -!- PTM: Ubiquitinated; restricts glucocorticoid-mediated CC transcriptional signaling. {ECO:0000250|UniProtKB:P06537}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14053; AAA41203.1; -; mRNA. DR EMBL; Y12264; CAA72938.1; -; mRNA. DR EMBL; AY066016; AAL66772.2; -; mRNA. DR EMBL; AF455050; AAL78956.1; -; mRNA. DR EMBL; Y00489; CAA68545.1; -; mRNA. DR EMBL; X69666; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X69667; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X69668; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X69669; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X69670; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A24194; QRRTG. DR RefSeq; NP_036708.2; NM_012576.2. DR UniGene; Rn.90070; -. DR PDB; 1GDC; NMR; -; A=439-510. DR PDB; 1GLU; X-ray; 2.90 A; A/B=440-514. DR PDB; 1LAT; X-ray; 1.90 A; A/B=440-515. DR PDB; 1R4O; X-ray; 2.50 A; A/B=440-525. DR PDB; 1R4R; X-ray; 3.00 A; A/B=440-525. DR PDB; 1RGD; NMR; -; A=440-510. DR PDB; 2GDA; NMR; -; A=439-510. DR PDB; 3FYL; X-ray; 1.63 A; A/B=440-525. DR PDB; 3G6P; X-ray; 1.99 A; A/B=440-525. DR PDB; 3G6Q; X-ray; 2.26 A; A/B=440-525. DR PDB; 3G6R; X-ray; 2.30 A; A/B=440-525. DR PDB; 3G6T; X-ray; 1.90 A; A/B=440-525. DR PDB; 3G6U; X-ray; 1.90 A; A/B=440-525. DR PDB; 3G8U; X-ray; 1.90 A; A/B=440-525. DR PDB; 3G8X; X-ray; 2.05 A; A/B=440-525. DR PDB; 3G97; X-ray; 2.08 A; A/B=440-525. DR PDB; 3G99; X-ray; 1.81 A; A/B=440-525. DR PDB; 3G9I; X-ray; 1.85 A; A/B=440-525. DR PDB; 3G9J; X-ray; 2.32 A; A/B=440-525. DR PDB; 3G9M; X-ray; 1.61 A; A/B=440-525. DR PDB; 3G9O; X-ray; 1.65 A; A/B=440-525. DR PDB; 3G9P; X-ray; 1.65 A; A/B=440-525. DR PDBsum; 1GDC; -. DR PDBsum; 1GLU; -. DR PDBsum; 1LAT; -. DR PDBsum; 1R4O; -. DR PDBsum; 1R4R; -. DR PDBsum; 1RGD; -. DR PDBsum; 2GDA; -. DR PDBsum; 3FYL; -. DR PDBsum; 3G6P; -. DR PDBsum; 3G6Q; -. DR PDBsum; 3G6R; -. DR PDBsum; 3G6T; -. DR PDBsum; 3G6U; -. DR PDBsum; 3G8U; -. DR PDBsum; 3G8X; -. DR PDBsum; 3G97; -. DR PDBsum; 3G99; -. DR PDBsum; 3G9I; -. DR PDBsum; 3G9J; -. DR PDBsum; 3G9M; -. DR PDBsum; 3G9O; -. DR PDBsum; 3G9P; -. DR ProteinModelPortal; P06536; -. DR SMR; P06536; -. DR BioGrid; 246578; 15. DR DIP; DIP-38940N; -. DR ELM; P06536; -. DR IntAct; P06536; 30. DR MINT; MINT-194828; -. DR STRING; 10116.ENSRNOP00000044335; -. DR BindingDB; P06536; -. DR ChEMBL; CHEMBL3368; -. DR iPTMnet; P06536; -. DR PhosphoSitePlus; P06536; -. DR PaxDb; P06536; -. DR PeptideAtlas; P06536; -. DR PRIDE; P06536; -. DR GeneID; 24413; -. DR KEGG; rno:24413; -. DR UCSC; RGD:2741; rat. [P06536-1] DR CTD; 2908; -. DR RGD; 2741; Nr3c1. DR eggNOG; KOG3575; Eukaryota. DR eggNOG; ENOG410XRZC; LUCA. DR HOGENOM; HOG000037950; -. DR HOVERGEN; HBG007583; -. DR InParanoid; P06536; -. DR KO; K05771; -. DR PhylomeDB; P06536; -. DR EvolutionaryTrace; P06536; -. DR PRO; PR:P06536; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; IDA:RGD. DR GO; GO:0043197; C:dendritic spine; IDA:RGD. DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0043005; C:neuron projection; IDA:RGD. DR GO; GO:0005634; C:nucleus; IDA:RGD. DR GO; GO:0014069; C:postsynaptic density; IDA:RGD. DR GO; GO:0043234; C:protein complex; IDA:RGD. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0003682; F:chromatin binding; IDA:RGD. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD. DR GO; GO:0038051; F:glucocorticoid-activated RNA polymerase II transcription factor binding transcription factor activity; ISS:UniProtKB. DR GO; GO:0031072; F:heat shock protein binding; IDA:RGD. DR GO; GO:0042562; F:hormone binding; IPI:RGD. DR GO; GO:0030544; F:Hsp70 protein binding; IDA:RGD. DR GO; GO:0051879; F:Hsp90 protein binding; IDA:RGD. DR GO; GO:0032403; F:protein complex binding; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; TAS:RGD. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:RGD. DR GO; GO:0042803; F:protein homodimerization activity; IDA:RGD. DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:RGD. DR GO; GO:0001012; F:RNA polymerase II regulatory region DNA binding; IDA:RGD. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD. DR GO; GO:0005496; F:steroid binding; IPI:RGD. DR GO; GO:1990239; F:steroid hormone binding; ISS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:RGD. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IMP:RGD. DR GO; GO:0008134; F:transcription factor binding; IPI:RGD. DR GO; GO:0008270; F:zinc ion binding; TAS:RGD. DR GO; GO:0007568; P:aging; IEP:RGD. DR GO; GO:0008209; P:androgen metabolic process; IEP:RGD. DR GO; GO:0007420; P:brain development; IEP:RGD. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IMP:RGD. DR GO; GO:0071286; P:cellular response to magnesium ion; IEP:RGD. DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; ISS:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IMP:UniProtKB. DR GO; GO:0048096; P:chromatin-mediated maintenance of transcription; IMP:UniProtKB. DR GO; GO:0007623; P:circadian rhythm; IEP:RGD. DR GO; GO:0016569; P:covalent chromatin modification; IEA:UniProtKB-KW. DR GO; GO:0007565; P:female pregnancy; IEP:RGD. DR GO; GO:0030324; P:lung development; IEP:RGD. DR GO; GO:0014889; P:muscle atrophy; IEP:RGD. DR GO; GO:0031914; P:negative regulation of synaptic plasticity; IMP:RGD. DR GO; GO:0043116; P:negative regulation of vascular permeability; IMP:RGD. DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IMP:RGD. DR GO; GO:0060999; P:positive regulation of dendritic spine development; IMP:RGD. DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; IDA:RGD. DR GO; GO:0014049; P:positive regulation of glutamate secretion; IMP:RGD. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:RGD. DR GO; GO:0042127; P:regulation of cell proliferation; IDA:RGD. DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:RGD. DR GO; GO:0014823; P:response to activity; IEP:RGD. DR GO; GO:0046685; P:response to arsenic-containing substance; IDA:RGD. DR GO; GO:0051592; P:response to calcium ion; IEP:RGD. DR GO; GO:0051412; P:response to corticosterone; IEP:RGD. DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD. DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD. DR GO; GO:0014854; P:response to inactivity; IEP:RGD. DR GO; GO:0032868; P:response to insulin; IEP:RGD. DR GO; GO:0046689; P:response to mercury ion; IEP:RGD. DR GO; GO:0009314; P:response to radiation; IEP:RGD. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 2.130.10.10; -; 1. DR Gene3D; 3.30.50.10; -; 1. DR InterPro; IPR001409; Glcrtcd_rcpt. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR Pfam; PF02155; GCR; 2. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00528; GLCORTICOIDR. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF48508; SSF48508; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; KW Chromatin regulator; Complete proteome; Cytoplasm; Cytoskeleton; KW DNA-binding; Isopeptide bond; Lipid-binding; Metal-binding; KW Methylation; Mitochondrion; Nucleus; Phosphoprotein; Polymorphism; KW Receptor; Reference proteome; Steroid-binding; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 795 Glucocorticoid receptor. FT /FTId=PRO_0000019941. FT DNA_BIND 440 505 Nuclear receptor. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT ZN_FING 440 460 NR C4-type. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT ZN_FING 476 500 NR C4-type. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT REGION 1 439 Modulating. FT REGION 504 795 Interaction with CLOCK. {ECO:0000250}. FT REGION 506 546 Hinge. FT REGION 547 795 Steroid-binding. FT REGION 550 715 Interaction with CRY1. {ECO:0000250}. FT COMPBIAS 75 97 Poly-Gln. FT COMPBIAS 419 438 Glu/Pro/Ser/Thr-rich (PEST region). FT MOD_RES 24 24 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:P06537}. FT MOD_RES 46 46 Phosphoserine. FT {ECO:0000250|UniProtKB:P04150}. FT MOD_RES 134 134 Phosphoserine. FT {ECO:0000250|UniProtKB:P06537}. FT MOD_RES 155 155 Phosphoserine. FT {ECO:0000250|UniProtKB:P04150}. FT MOD_RES 162 162 Phosphoserine. FT {ECO:0000250|UniProtKB:P06537}. FT MOD_RES 171 171 Phosphothreonine. FT {ECO:0000269|PubMed:9603939}. FT MOD_RES 224 224 Phosphoserine. FT {ECO:0000244|PubMed:22673903, FT ECO:0000269|PubMed:9603939}. FT MOD_RES 232 232 Phosphoserine. FT {ECO:0000244|PubMed:22673903, FT ECO:0000269|PubMed:9603939}. FT MOD_RES 246 246 Phosphoserine. FT {ECO:0000269|PubMed:9603939}. FT MOD_RES 287 287 Phosphoserine. FT {ECO:0000244|PubMed:22673903}. FT MOD_RES 327 327 Phosphoserine. FT {ECO:0000250|UniProtKB:P06537}. FT MOD_RES 424 424 Phosphoserine. FT {ECO:0000250|UniProtKB:P04150}. FT MOD_RES 499 499 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P04150}. FT MOD_RES 511 511 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P04150}. FT MOD_RES 513 513 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P04150}. FT MOD_RES 514 514 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P04150}. FT CROSSLNK 278 278 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000250|UniProtKB:P04150}. FT CROSSLNK 297 297 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. {ECO:0000269|PubMed:23508108}. FT CROSSLNK 297 297 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. FT {ECO:0000250|UniProtKB:P04150}. FT CROSSLNK 313 313 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. {ECO:0000269|PubMed:23508108}. FT CROSSLNK 313 313 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. FT {ECO:0000250|UniProtKB:P04150}. FT CROSSLNK 721 721 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT {ECO:0000269|PubMed:23508108}. FT VAR_SEQ 1 27 Missing (in isoform B). {ECO:0000305}. FT /FTId=VSP_018969. FT VARIANT 77 77 Missing (in strain: Brown Norway/Crl). FT VARIANT 78 79 Missing (in strain: SHR/OlaIpcv). FT VARIANT 83 96 Missing (in strain: Sprague-Dawley). FT VARIANT 226 226 S -> G (in strain: SHR/OlaIpcv and Brown FT Norway/Crl). FT {ECO:0000244|PubMed:22673903, FT ECO:0000269|Ref.3}. FT VARIANT 260 260 N -> D (in strain: SHR/OlaIpcv and Brown FT Norway/Crl). {ECO:0000269|Ref.3}. FT MUTAGEN 1 1 M->T: Abolishes expression of A-type FT isoforms. {ECO:0000269|PubMed:11435610}. FT MUTAGEN 28 28 M->T: Abolishes expression of B-type FT isoforms. {ECO:0000269|PubMed:11435610}. FT MUTAGEN 297 297 K->R: Enhances transcriptional activity; FT when associated with R-313. FT {ECO:0000269|PubMed:23508108}. FT MUTAGEN 313 313 K->R: Enhances transcriptional activity; FT when associated with R-297. FT {ECO:0000269|PubMed:23508108}. FT MUTAGEN 481 481 D->R: Disrupts dimerization and decreases FT transcription transactivation. FT {ECO:0000269|PubMed:8618925}. FT MUTAGEN 488 488 R->Q: Loss of chromatin specific function FT and reduces chromatin remodeling. FT Abolishes interaction with SMARD1. FT {ECO:0000269|PubMed:12917342}. FT MUTAGEN 500 500 C->Y: Abolishes interaction with POU2F2. FT {ECO:0000269|PubMed:10480874}. FT MUTAGEN 501 501 L->P: Abrogates DNA-binding and FT transcription transactivation. Abolishes FT interaction with POU2F1 and POU2F2. FT {ECO:0000269|PubMed:10480874, FT ECO:0000269|PubMed:11278286}. FT MUTAGEN 656 656 C->S: Strongly increases affinity for FT dexamethasone. FT {ECO:0000269|PubMed:1939229}. FT MUTAGEN 721 721 K->R: Abolishes the stimulatory effect of FT RWDD3 on its transcriptional activity. FT Diminishes NCOA2 coactivator activity. FT {ECO:0000269|PubMed:23508108}. FT MUTAGEN 773 773 E->A: Abolishes interaction with NCOA1 FT and reduces transcription FT transactivation; when associated with S- FT 656. {ECO:0000269|PubMed:12118039}. FT CONFLICT 95 96 Missing (in Ref. 3; AAL78956). FT {ECO:0000305}. FT CONFLICT 98 98 D -> G (in Ref. 1; AAA41203). FT {ECO:0000305}. FT CONFLICT 345 345 S -> T (in Ref. 4; CAA68545). FT {ECO:0000305}. FT CONFLICT 600 600 L -> P (in Ref. 2; CAA72938 and 3; FT AAL66772/AAL78956). {ECO:0000305}. FT CONFLICT 602 602 L -> F (in Ref. 3; AAL66772/AAL78956). FT {ECO:0000305}. FT TURN 441 443 {ECO:0000244|PDB:3G9M}. FT STRAND 444 446 {ECO:0000244|PDB:3G97}. FT STRAND 449 451 {ECO:0000244|PDB:3G9M}. FT STRAND 454 456 {ECO:0000244|PDB:3G9M}. FT HELIX 458 469 {ECO:0000244|PDB:3G9M}. FT STRAND 477 480 {ECO:0000244|PDB:3G9M}. FT HELIX 488 490 {ECO:0000244|PDB:3G9M}. FT HELIX 493 503 {ECO:0000244|PDB:3G9M}. FT HELIX 509 513 {ECO:0000244|PDB:3G9M}. SQ SEQUENCE 795 AA; 87556 MW; 9C9DE0B1D6724845 CRC64; MDSKESLAPP GRDEVPGSLL GQGRGSVMDF YKSLRGGATV KVSASSPSVA AASQADSKQQ RILLDFSKGS TSNVQQRQQQ QQQQQQQQQQ QQQQQQPDLS KAVSLSMGLY MGETETKVMG NDLGYPQQGQ LGLSSGETDF RLLEESIANL NRSTSVPENP KSSTSATGCA TPTEKEFPKT HSDASSEQQN RKSQTGTNGG SVKLYPTDQS TFDLLKDLEF SAGSPSKDTN ESPWRSDLLI DENLLSPLAG EDDPFLLEGN TNEDCKPLIL PDTKPKIKDT GDTILSSPSS VALPQVKTEK DDFIELCTPG VIKQEKLGPV YCQASFSGTN IIGNKMSAIS VHGVSTSGGQ MYHYDMNTAS LSQQQDQKPV FNVIPPIPVG SENWNRCQGS GEDSLTSLGA LNFPGRSVFS NGYSSPGMRP DVSSPPSSSS AATGPPPKLC LVCSDEASGC HYGVLTCGSC KVFFKRAVEG QHNYLCAGRN DCIIDKIRRK NCPACRYRKC LQAGMNLEAR KTKKKIKGIQ QATAGVSQDT SENPNKTIVP AALPQLTPTL VSLLEVIEPE VLYAGYDSSV PDSAWRIMTT LNMLGGRQVI AAVKWAKAIL GLRNLHLDDQ MTLLQYSWMF LMAFALGWRS YRQSSGNLLC FAPDLIINEQ RMSLPCMYDQ CKHMLFVSSE LQRLQVSYEE YLCMKTLLLL SSVPKEGLKS QELFDEIRMT YIKELGKAIV KREGNSSQNW QRFYQLTKLL DSMHEVVENL LTYCFQTFLD KTMSIEFPEM LAEIITNQIP KYSNGNIKKL LFHQK //