ID GCR_HUMAN Reviewed; 777 AA. AC P04150; A0ZXF9; B0LPG8; D3DQF4; F5ATB7; P04151; Q53EP5; Q6N0A4; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 27-MAR-2024, entry version 285. DE RecName: Full=Glucocorticoid receptor; DE Short=GR; DE AltName: Full=Nuclear receptor subfamily 3 group C member 1; GN Name=NR3C1 {ECO:0000312|HGNC:HGNC:7978}; Synonyms=GRL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). RC TISSUE=Fibroblast; RX PubMed=2867473; DOI=10.1038/318635a0; RA Hollenberg S.M., Weinberger C., Ong E.S., Cerelli G., Oro A., Lebo R., RA Thompson E.B., Rosenfeld M.G., Evans R.M.; RT "Primary structure and expression of a functional human glucocorticoid RT receptor cDNA."; RL Nature 318:635-641(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS ALPHA AND BETA). RX PubMed=1707881; DOI=10.1016/s0021-9258(20)89627-6; RA Encio I.J., Detera-Wadleigh S.D.; RT "The genomic structure of the human glucocorticoid receptor."; RL J. Biol. Chem. 266:7182-7188(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=20843780; DOI=10.1093/nar/gkq750; RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R., RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M., RA Speed T.P., Scharfe C.; RT "Identification of rare DNA variants in mitochondrial disorders with RT improved array-based sequencing."; RL Nucleic Acids Res. 39:44-58(2011). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 10). RX PubMed=17404046; DOI=10.1196/annals.1397.037; RA Turner J.D., Schote A.B., Keipes M., Muller C.P.; RT "A new transcript splice variant of the human glucocorticoid receptor: RT identification and tissue distribution of hGR Delta 313-338, an alternative RT exon 2 transactivation domain isoform."; RL Ann. N. Y. Acad. Sci. 1095:334-341(2007). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), VARIANTS ASP-72; ALA-321 AND RP SER-766, AND CHARACTERIZATION OF VARIANTS ASP-72; ALA-321 AND SER-766. RX PubMed=21701417; DOI=10.1097/shk.0b013e318228eca7; RA Tung K., Baker A.C., Amini A., Green T.L., Chew V.W., Lim D., Nguyen S.T., RA Yee K.S., Cho K., Greenhalgh D.G.; RT "Novel hyperactive glucocorticoid receptor isoform identified within a RT human population."; RL Shock 36:339-344(2011). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA-2). RC TISSUE=Osteosarcoma; RA Munroe D.G., Pang J., Taylor G.R., Lau C., Plante R.K., Zhou L.; RT "Alternative splicing within the DNA binding domain creates a novel isoform RT of the human glucocorticoid receptor."; RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Kidney; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Uterine endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LYS-23 AND VAL-65. RG NIEHS SNPs program; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-394. RX PubMed=2026589; DOI=10.1016/s0021-9258(18)31504-7; RA Leclerc S., Xie B.X., Roy R., Govindan M.V.; RT "Purification of a human glucocorticoid receptor gene promoter-binding RT protein. Production of polyclonal antibodies against the purified factor."; RL J. Biol. Chem. 266:8711-8719(1991). RN [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-394. RX PubMed=1958537; DOI=10.1016/0960-0760(91)90197-d; RA Govindan M.V., Pothier F., Leclerc S., Palaniswami R., Xie B.; RT "Human glucocorticoid receptor gene promotor-homologous down regulation."; RL J. Steroid Biochem. Mol. Biol. 40:317-323(1991). RN [16] RP DOMAINS. RX PubMed=3841189; DOI=10.1038/318670a0; RA Weinberger C., Hollenberg S.M., Rosenfeld M.G., Evans R.M.; RT "Domain structure of human glucocorticoid receptor and its relationship to RT the v-erb-A oncogene product."; RL Nature 318:670-672(1985). RN [17] RP ALTERNATIVE SPLICING (ISOFORMS GR-P; GR-A ALPHA AND GR-A BETA). RX PubMed=8358712; RA Moalli P.A., Pillay S., Krett N.L., Rosen S.T.; RT "Alternatively spliced glucocorticoid receptor messenger RNAs in RT glucocorticoid-resistant human multiple myeloma cells."; RL Cancer Res. 53:3877-3879(1993). RN [18] RP FUNCTION (ISOFORM BETA), AND TISSUE SPECIFICITY (ISOFORM BETA). RX PubMed=7769088; DOI=10.1172/jci117943; RA Bamberger C.M., Bamberger A.M., de Castro M., Chrousos G.P.; RT "Glucocorticoid receptor beta, a potential endogenous inhibitor of RT glucocorticoid action in humans."; RL J. Clin. Invest. 95:2435-2441(1995). RN [19] RP FUNCTION (ISOFORM BETA), SUBCELLULAR LOCATION (ISOFORMS ALPHA AND BETA), RP AND TISSUE SPECIFICITY (ISOFORM BETA). RX PubMed=8621628; DOI=10.1074/jbc.271.16.9550; RA Oakley R.H., Sar M., Cidlowski J.A.; RT "The human glucocorticoid receptor beta isoform. Expression, biochemical RT properties, and putative function."; RL J. Biol. Chem. 271:9550-9559(1996). RN [20] RP INTERACTION WITH HNRNPU. RX PubMed=9353307; DOI=10.1074/jbc.272.45.28471; RA Eggert M., Michel J., Schneider S., Bornfleth H., Baniahmad A., RA Fackelmayer F.O., Schmidt S., Renkawitz R.; RT "The glucocorticoid receptor is associated with the RNA-binding nuclear RT matrix protein hnRNP U."; RL J. Biol. Chem. 272:28471-28478(1997). RN [21] RP INTERACTION WITH TADA2L AND THE ADA COMPLEX, AND MUTAGENESIS OF PHE-191; RP ILE-193; LEU-194; LEU-197; TRP-213; LEU-224; LEU-225; PHE-235 AND LEU-236. RX PubMed=9154805; DOI=10.1128/mcb.17.6.3065; RA Henriksson A., Almloef T., Ford J., McEwan I.J., Gustafsson J.-A., RA Wright A.P.H.; RT "Role of the Ada adaptor complex in gene activation by the glucocorticoid RT receptor."; RL Mol. Cell. Biol. 17:3065-3073(1997). RN [22] RP FUNCTION, AND INTERACTION WITH THE SMARCA4 COMPLEX; NCOA1; NCOA2 AND THE RP CREBBP/EP300 COMPLEX. RX PubMed=9590696; DOI=10.1038/30032; RA Fryer C.J., Archer T.K.; RT "Chromatin remodelling by the glucocorticoid receptor requires the BRG1 RT complex."; RL Nature 393:88-91(1998). RN [23] RP INTERACTION WITH BAG1. RX PubMed=10477749; DOI=10.1083/jcb.146.5.929; RA Schneikert J., Huebner S., Martin E., Cato A.B.C.; RT "A nuclear action of the eukaryotic cochaperone RAP46 in downregulation of RT glucocorticoid receptor activity."; RL J. Cell Biol. 146:929-940(1999). RN [24] RP ALTERNATIVE SPLICING (ISOFORMS ALPHA-2 AND BETA-2), AND TISSUE SPECIFICITY RP (ISOFORM ALPHA-2). RX PubMed=10566686; DOI=10.1210/jcem.84.11.6235; RA Rivers C., Levy A., Hancock J., Lightman S., Norman M.; RT "Insertion of an amino acid in the DNA-binding domain of the glucocorticoid RT receptor as a result of alternative splicing."; RL J. Clin. Endocrinol. Metab. 84:4283-4286(1999). RN [25] RP TISSUE SPECIFICITY. RX PubMed=10902803; DOI=10.1210/jcem.85.7.6663; RA Kayes-Wandover K.M., White P.C.; RT "Steroidogenic enzyme gene expression in the human heart."; RL J. Clin. Endocrinol. Metab. 85:2519-2525(2000). RN [26] 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 [27] RP EFFECT ON EXPANDED POLYGLUTAMINE PROTEIN. RX PubMed=10639135; DOI=10.1073/pnas.97.2.657; RA Diamond M.I., Robinson M.R., Yamamoto K.R.; RT "Regulation of expanded polyglutamine protein aggregation and nuclear RT localization by the glucocorticoid receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 97:657-661(2000). RN [28] RP FUNCTION (ISOFORM GR-P). RX PubMed=11358809; RA de Lange P., Segeren C.M., Koper J.W., Wiemer E., Sonneveld P., RA Brinkmann A.O., White A., Brogan I.J., de Jong F.H., Lamberts S.W.; RT "Expression in hematological malignancies of a glucocorticoid receptor RT splice variant that augments glucocorticoid receptor-mediated effects in RT transfected cells."; RL Cancer Res. 61:3937-3941(2001). RN [29] RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION. RX PubMed=11555652; DOI=10.1074/jbc.m106033200; RA Wallace A.D., Cidlowski J.A.; RT "Proteasome-mediated glucocorticoid receptor degradation restricts RT transcriptional signaling by glucocorticoids."; RL J. Biol. Chem. 276:42714-42721(2001). RN [30] RP REDUCTION OF CELL DEATH IN RESPONSE TO CORTICOSTEROIDS. RX PubMed=11238589; DOI=10.1084/jem.193.5.585; RA Strickland I., Kisich K., Hauk P.J., Vottero A., Chrousos G.P., Klemm D.J., RA Leung D.Y.M.; RT "High constitutive glucocorticoid receptor beta in human neutrophils RT enables them to reduce their spontaneous rate of cell death in response to RT corticosteroids."; RL J. Exp. Med. 193:585-593(2001). RN [31] RP FUNCTION (ISOFORMS ALPHA AND ALPHA-B), ALTERNATIVE INITIATION, AND RP MUTAGENESIS OF MET-1 AND MET-27. 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 [32] RP INDUCTION (ISOFORMS ALPHA AND BETA). RX PubMed=11381138; DOI=10.1073/pnas.121455098; RA Webster J.C., Oakley R.H., Jewell C.M., Cidlowski J.A.; RT "Proinflammatory cytokines regulate human glucocorticoid receptor gene RT expression and lead to the accumulation of the dominant negative beta RT isoform: a mechanism for the generation of glucocorticoid resistance."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6865-6870(2001). RN [33] RP SUMOYLATION, AND MUTAGENESIS OF LYS-277; LYS-293 AND LYS-703. RX PubMed=12144530; DOI=10.1042/bj20021085; RA Tian S., Poukka H., Palvimo J.J., Jaenne O.A.; RT "Small ubiquitin-related modifier-1 (SUMO-1) modification of the RT glucocorticoid receptor."; RL Biochem. J. 367:907-911(2002). RN [34] RP PHOSPHORYLATION AT SER-203 AND SER-211. RX PubMed=12000743; DOI=10.1074/jbc.m110530200; RA Wang Z., Frederick J., Garabedian M.J.; RT "Deciphering the phosphorylation 'code' of the glucocorticoid receptor in RT vivo."; RL J. Biol. Chem. 277:26573-26580(2002). RN [35] RP RETRACTED PAPER. RX PubMed=12415108; DOI=10.1073/pnas.192569699; RA Wong C.-W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.; RT "Estrogen receptor-interacting protein that modulates its nongenomic RT activity-crosstalk with Src/Erk phosphorylation cascade."; RL Proc. Natl. Acad. Sci. U.S.A. 99:14783-14788(2002). RN [36] RP RETRACTION NOTICE OF PUBMED:12415108. RX PubMed=19666546; DOI=10.1073/pnas.0908685106; RA Wong C.W., McNally C., Nickbarg E., Komm B.S., Cheskis B.J.; RL Proc. Natl. Acad. Sci. U.S.A. 106:14180-14180(2009). RN [37] RP REVIEW ON ALTERNATIVE SPLICING, AND ALTERNATIVE INITIATION. RX PubMed=15265776; DOI=10.1196/annals.1321.008; RA Lu N.Z., Cidlowski J.A.; RT "The origin and functions of multiple human glucocorticoid receptor RT isoforms."; RL Ann. N. Y. Acad. Sci. 1024:102-123(2004). RN [38] RP INTERACTION WITH TGFB1I1. RX PubMed=15211577; DOI=10.1002/jcb.20109; RA Guerrero-Santoro J., Yang L., Stallcup M.R., DeFranco D.B.; RT "Distinct LIM domains of Hic-5/ARA55 are required for nuclear matrix RT targeting and glucocorticoid receptor binding and coactivation."; RL J. Cell. Biochem. 92:810-819(2004). RN [39] RP FUNCTION (ISOFORMS ALPHA; ALPHA-B; ALPHA-C1; ALPHA-C2; ALPHA-C3; ALPHA-D1; RP ALPHA-D2 AND ALPHA-D3), SUBCELLULAR LOCATION (ISOFORM ALPHA-B), ALTERNATIVE RP INITIATION (ISOFORMS ALPHA; ALPHA-B; ALPHA-C1; ALPHA-C2; ALPHA-C3; RP ALPHA-D1; ALPHA-D2 AND ALPHA-D3), AND MUTAGENESIS OF MET-1; MET-27; MET-86; RP MET-90; MET-98; MET-316; MET-331 AND MET-336. RX PubMed=15866175; DOI=10.1016/j.molcel.2005.03.025; RA Lu N.Z., Cidlowski J.A.; RT "Translational regulatory mechanisms generate N-terminal glucocorticoid RT receptor isoforms with unique transcriptional target genes."; RL Mol. Cell 18:331-342(2005). RN [40] RP INTERACTION WITH NR4A3. RX PubMed=15591535; DOI=10.1210/me.2004-0333; RA Martens C., Bilodeau S., Maira M., Gauthier Y., Drouin J.; RT "Protein-protein interactions and transcriptional antagonism between the RT subfamily of NGFI-B/Nur77 orphan nuclear receptors and glucocorticoid RT receptor."; RL Mol. Endocrinol. 19:885-897(2005). RN [41] RP INTERACTION WITH HEXIM1. RX PubMed=15941832; DOI=10.1073/pnas.0409863102; RA Shimizu N., Ouchida R., Yoshikawa N., Hisada T., Watanabe H., Okamoto K., RA Kusuhara M., Handa H., Morimoto C., Tanaka H.; RT "HEXIM1 forms a transcriptionally abortive complex with glucocorticoid RT receptor without involving 7SK RNA and positive transcription elongation RT factor b."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8555-8560(2005). RN [42] RP INTERACTION WITH MCM3AP. RX PubMed=16914116; DOI=10.1016/j.bbrc.2006.07.182; RA Osman W., Laine S., Zilliacus J.; RT "Functional interaction between the glucocorticoid receptor and RT GANP/MCM3AP."; RL Biochem. Biophys. Res. Commun. 348:1239-1244(2006). RN [43] RP INTERACTION WITH UNC45A. RX PubMed=16478993; DOI=10.1128/mcb.26.5.1722-1730.2006; RA Chadli A., Graham J.D., Abel M.G., Jackson T.A., Gordon D.F., Wood W.M., RA Felts S.J., Horwitz K.B., Toft D.; RT "GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 RT chaperoning pathway."; RL Mol. Cell. Biol. 26:1722-1730(2006). RN [44] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [46] RP INTERACTION WITH GSK3B, SUBCELLULAR LOCATION (ISOFORM ALPHA), RP PHOSPHORYLATION AT SER-404, MUTAGENESIS OF SER-404, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=18838540; DOI=10.1128/mcb.00808-08; RA Galliher-Beckley A.J., Williams J.G., Collins J.B., Cidlowski J.A.; RT "Glycogen synthase kinase 3beta-mediated serine phosphorylation of the RT human glucocorticoid receptor redirects gene expression profiles."; RL Mol. Cell. Biol. 28:7309-7322(2008). RN [47] RP PHOSPHORYLATION AT SER-203; SER-211 AND SER-226, AND MUTAGENESIS OF SER-211 RP AND SER-226. RX PubMed=18483179; DOI=10.1210/me.2007-0219; RA Chen W., Dang T., Blind R.D., Wang Z., Cavasotto C.N., Hittelman A.B., RA Rogatsky I., Logan S.K., Garabedian M.J.; RT "Glucocorticoid receptor phosphorylation differentially affects target gene RT expression."; RL Mol. Endocrinol. 22:1754-1766(2008). RN [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134; SER-226 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [49] RP FUNCTION (ISOFORMS ALPHA AND BETA), AND SUBCELLULAR LOCATION (ISOFORM RP BETA). RX PubMed=19248771; DOI=10.1016/j.bbrc.2009.02.110; RA Kino T., Manoli I., Kelkar S., Wang Y., Su Y.A., Chrousos G.P.; RT "Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent RT transcriptional activity."; RL Biochem. Biophys. Res. Commun. 381:671-675(2009). RN [50] RP FUNCTION (ISOFORM ALPHA), ACETYLATION AT LYS-480; LYS-492; LYS-494 AND RP LYS-495, MUTAGENESIS OF LYS-480; LYS-492; LYS-494 AND LYS-495, AND RP INTERACTION WITH CLOCK. RX PubMed=19141540; DOI=10.1096/fj.08-117697; RA Nader N., Chrousos G.P., Kino T.; RT "Circadian rhythm transcription factor CLOCK regulates the transcriptional RT activity of the glucocorticoid receptor by acetylating its hinge region RT lysine cluster: potential physiological implications."; RL FASEB J. 23:1572-1583(2009). RN [51] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [52] RP INTERACTION WITH TACC1. RX PubMed=20078863; DOI=10.1186/1471-2199-11-3; RA Guyot R., Vincent S., Bertin J., Samarut J., Ravel-Chapuis P.; RT "The transforming acidic coiled coil (TACC1) protein modulates the RT transcriptional activity of the nuclear receptors TR and RAR."; RL BMC Mol. Biol. 11:3-3(2010). RN [53] RP FUNCTION (ISOFORMS ALPHA; BETA; ALPHA-2 AND 10). RX PubMed=20484466; DOI=10.1210/en.2009-1254; RA Taniguchi Y., Iwasaki Y., Tsugita M., Nishiyama M., Taguchi T., Okazaki M., RA Nakayama S., Kambayashi M., Hashimoto K., Terada Y.; RT "Glucocorticoid receptor-beta and receptor-gamma exert dominant negative RT effect on gene repression but not on gene induction."; RL Endocrinology 151:3204-3213(2010). RN [54] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [55] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [56] RP FUNCTION (ISOFORM ALPHA), AND SUBCELLULAR LOCATION (ISOFORM ALPHA). RX PubMed=21664385; DOI=10.1016/j.bbamcr.2011.05.014; RA Psarra A.M., Sekeris C.E.; RT "Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: RT role of the mitochondrial glucocorticoid receptor."; RL Biochim. Biophys. Acta 1813:1814-1821(2011). RN [57] RP SUBUNIT. 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 a RT mitochondrial protein that translocates to the nucleus to protect cells RT against oxidative stress."; RL J. Biol. Chem. 286:30152-30160(2011). RN [58] RP INTERACTION WITH CRY1 AND CRY2. RX PubMed=22170608; DOI=10.1038/nature10700; RA Lamia K.A., Papp S.J., Yu R.T., Barish G.D., Uhlenhaut N.H., Jonker J.W., RA Downes M., Evans R.M.; RT "Cryptochromes mediate rhythmic repression of the glucocorticoid RT receptor."; RL Nature 480:552-556(2011). RN [59] RP ACETYLATION, AND INTERACTION WITH CLOCK. RX PubMed=21980503; DOI=10.1371/journal.pone.0025612; RA Charmandari E., Chrousos G.P., Lambrou G.I., Pavlaki A., Koide H., Ng S.S., RA Kino T.; RT "Peripheral CLOCK regulates target-tissue glucocorticoid receptor RT transcriptional activity in a circadian fashion in man."; RL PLoS ONE 6:E25612-E25612(2011). RN [60] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORMS ALPHA-B AND BETA-B), RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [61] RP FUNCTION (ISOFORMS ALPHA; ALPHA-C3 AND ALPHA-D3). RX PubMed=23303127; DOI=10.1038/cddis.2012.193; RA Wu I., Shin S.C., Cao Y., Bender I.K., Jafari N., Feng G., Lin S., RA Cidlowski J.A., Schleimer R.P., Lu N.Z.; RT "Selective glucocorticoid receptor translational isoforms reveal RT glucocorticoid-induced apoptotic transcriptomes."; RL Cell Death Dis. 4:E453-E453(2013). RN [62] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8; SER-45 AND SER-267, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [63] RP MUTAGENESIS OF LYS-703. RX PubMed=23508108; DOI=10.1128/mcb.01470-12; RA Druker J., Liberman A.C., Antunica-Noguerol M., Gerez J., Paez-Pereda M., RA Rein T., Iniguez-Lluhi J.A., Holsboer F., Arzt E.; RT "RSUME enhances glucocorticoid receptor SUMOylation and transcriptional RT activity."; RL Mol. Cell. Biol. 33:2116-2127(2013). RN [64] RP FUNCTION (ISOFORMS ALPHA; ALPHA-C3 AND ALPHA-D3), AND MUTAGENESIS OF RP ASP-101; 106-GLN-GLN-107 AND 113-SER-SER-114. RX PubMed=23820903; DOI=10.1210/me.2013-1009; RA Bender I.K., Cao Y., Lu N.Z.; RT "Determinants of the heightened activity of glucocorticoid receptor RT translational isoforms."; RL Mol. Endocrinol. 27:1577-1587(2013). RN [65] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [66] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-293, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25114211; DOI=10.1073/pnas.1413825111; RA Impens F., Radoshevich L., Cossart P., Ribet D.; RT "Mapping of SUMO sites and analysis of SUMOylation changes induced by RT external stimuli."; RL Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014). RN [67] RP FUNCTION (ISOFORM BETA), AND SUBCELLULAR LOCATION (ISOFORM BETA). RX PubMed=26711253; DOI=10.1128/mcb.00908-15; RA He B., Cruz-Topete D., Oakley R.H., Xiao X., Cidlowski J.A.; RT "Human Glucocorticoid Receptor beta (hGRbeta) Regulates Gluconeogenesis and RT Inflammation in Mouse Liver."; RL Mol. Cell. Biol. 36:714-730(2015). RN [68] RP FUNCTION, AND INTERACTION WITH PNRC2. RX PubMed=25775514; DOI=10.1073/pnas.1409612112; RA Cho H., Park O.H., Park J., Ryu I., Kim J., Ko J., Kim Y.K.; RT "Glucocorticoid receptor interacts with PNRC2 in a ligand-dependent manner RT to recruit UPF1 for rapid mRNA degradation."; RL Proc. Natl. Acad. Sci. U.S.A. 112:E1540-E1549(2015). RN [69] RP FUNCTION (ISOFORM ALPHA), SUBCELLULAR LOCATION (ISOFORM ALPHA), TISSUE RP SPECIFICITY, DOMAIN, AND PHOSPHORYLATION AT SER-203 AND SER-211. RX PubMed=25847991; DOI=10.1073/pnas.1411356112; RA Matthews L.C., Berry A.A., Morgan D.J., Poolman T.M., Bauer K., Kramer F., RA Spiller D.G., Richardson R.V., Chapman K.E., Farrow S.N., Norman M.R., RA Williamson A.J., Whetton A.D., Taylor S.S., Tuckermann J.P., White M.R., RA Ray D.W.; RT "Glucocorticoid receptor regulates accurate chromosome segregation and is RT associated with malignancy."; RL Proc. Natl. Acad. Sci. U.S.A. 112:5479-5484(2015). RN [70] RP INTERACTION WITH FNIP1 AND FNIP2. RX PubMed=27353360; DOI=10.1038/ncomms12037; RA Woodford M.R., Dunn D.M., Blanden A.R., Capriotti D., Loiselle D., RA Prodromou C., Panaretou B., Hughes P.F., Smith A., Ackerman W., RA Haystead T.A., Loh S.N., Bourboulia D., Schmidt L.S., Marston Linehan W., RA Bratslavsky G., Mollapour M.; RT "The FNIP co-chaperones decelerate the Hsp90 chaperone cycle and enhance RT drug binding."; RL Nat. Commun. 7:12037-12037(2016). RN [71] RP IDENTIFICATION IN A COMPLEX WITH HSP90; HSP70; CDC37; PPP5C; TSC1; TSC2; RP AKT; CDK4 AND RAF1. RX PubMed=29127155; DOI=10.15252/embj.201796700; RA Woodford M.R., Sager R.A., Marris E., Dunn D.M., Blanden A.R., Murphy R.L., RA Rensing N., Shapiro O., Panaretou B., Prodromou C., Loh S.N., Gutmann D.H., RA Bourboulia D., Bratslavsky G., Wong M., Mollapour M.; RT "Tumor suppressor Tsc1 is a new Hsp90 co-chaperone that facilitates folding RT of kinase and non-kinase clients."; RL EMBO J. 36:3650-3665(2017). RN [72] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-258 AND LYS-277, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [73] RP FUNCTION, AND INTERACTION WITH ZNF764. RX PubMed=28139699; DOI=10.1038/srep41598; RA Fadda A., Syed N., Mackeh R., Papadopoulou A., Suzuki S., Jithesh P.V., RA Kino T.; RT "Genome-wide Regulatory Roles of the C2H2-type Zinc Finger Protein ZNF764 RT on the Glucocorticoid Receptor."; RL Sci. Rep. 7:41598-41598(2017). RN [74] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 521-777 OF MUTANT SER-602 IN RP COMPLEX WITH NCOA2; DEXAMETHASONE AND RU-486, AND MUTAGENESIS OF ARG-585; RP ASP-590; PHE-602; PRO-625 AND ILE-628. RX PubMed=12151000; DOI=10.1016/s0092-8674(02)00817-6; RA Bledsoe R.K., Montana V.G., Stanley T.B., Delves C.J., Apolito C.J., RA McKee D.D., Consler T.G., Parks D.J., Stewart E.L., Willson T.M., RA Lambert M.H., Moore J.T., Pearce K.H., Xu H.E.; RT "Crystal structure of the glucocorticoid receptor ligand binding domain RT reveals a novel mode of receptor dimerization and coactivator RT recognition."; RL Cell 110:93-105(2002). RN [75] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 500-777 OF MUTANT SER-602 IN RP COMPLEX WITH COACTIVATOR PEPTIDE; DEXAMETHASONE AND WITH RU-486. RX PubMed=12686538; DOI=10.1074/jbc.m212711200; RA Kauppi B., Jakob C., Faernegaardh M., Yang J., Ahola H., Alarcon M., RA Calles K., Engstrom O., Harlan J., Muchmore S., Ramqvist A.-K., Thorell S., RA Oehman L., Greer J., Gustafsson J.-A., Carlstedt-Duke J., Carlquist M.; RT "The three-dimensional structures of antagonistic and agonistic forms of RT the glucocorticoid receptor ligand-binding domain: RU-486 induces a RT transconformation that leads to active antagonism."; RL J. Biol. Chem. 278:22748-22754(2003). RN [76] RP CHARACTERIZATION OF VARIANT GCCR VAL-641. RX PubMed=1704018; DOI=10.1172/jci115046; RA Hurley D.M., Accili D., Stratakis C.A., Karl M., Vamvakopoulos N., RA Rorer E., Constantine K., Taylor S.I., Chrousos G.P.; RT "Point mutation causing a single amino acid substitution in the hormone RT binding domain of the glucocorticoid receptor in familial glucocorticoid RT resistance."; RL J. Clin. Invest. 87:680-686(1991). RN [77] RP VARIANTS TYR-421 AND PHE-753. RX PubMed=8358735; RA Powers J.H., Hillmann A.G., Tang D.C., Harmon J.M.; RT "Cloning and expression of mutant glucocorticoid receptors from RT glucocorticoid-sensitive and -resistant human leukemic cells."; RL Cancer Res. 53:4059-4065(1993). RN [78] RP VARIANT SER-363. RX PubMed=8445027; DOI=10.1210/jcem.76.3.8445027; RA Karl M., Lamberts S.W.J., Detera-Wadleigh S.D., Encio I.J., Stratakis C.A., RA Hurley D.M., Accili D., Chrousos G.P.; RT "Familial glucocorticoid resistance caused by a splice site deletion in the RT human glucocorticoid receptor gene."; RL J. Clin. Endocrinol. Metab. 76:683-689(1993). RN [79] RP VARIANT GCCR ILE-729. RX PubMed=7683692; DOI=10.1172/jci116410; RA Malchoff D.M., Brufsky A., Reardon G., McDermott P., Javier E.C., RA Bergh C.H., Rowe D., Malchoff C.D.; RT "A mutation of the glucocorticoid receptor in primary cortisol RT resistance."; RL J. Clin. Invest. 91:1918-1925(1993). RN [80] RP VARIANT PHE-753. RX PubMed=8316249; DOI=10.1210/mend.7.5.8316249; RA Ashraf J., Thompson E.B.; RT "Identification of the activation-labile gene: a single point mutation in RT the human glucocorticoid receptor presents as two distinct receptor RT phenotypes."; RL Mol. Endocrinol. 7:631-642(1993). RN [81] RP VARIANTS LYS-23 AND SER-363. RX PubMed=9150737; DOI=10.1007/s004390050425; RA Koper J.W., Stolk R.P., de Lange P., Huizenga N.A.T.M., Molijn G.-J., RA Pols H.A.P., Grobbee D.E., Karl M., de Jong F.H., Brinkmann A.O., RA Lamberts S.W.J.; RT "Lack of association between five polymorphisms in the human glucocorticoid RT receptor gene and glucocorticoid resistance."; RL Hum. Genet. 99:663-668(1997). RN [82] RP VARIANTS LYS-23; VAL-65 AND SER-363. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [83] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [84] RP VARIANTS LYS-23; LEU-29; PHE-112; ASN-233 AND SER-363. RX PubMed=10898924; RX DOI=10.1002/1096-8628(20000612)96:3<412::aid-ajmg33>3.0.co;2-c; RA Feng J., Zheng J., Bennett W.P., Heston L.L., Jones I.R., Craddock N., RA Sommer S.S.; RT "Five missense variants in the amino-terminal domain of the glucocorticoid RT receptor: no association with puerperal psychosis or schizophrenia."; RL Am. J. Med. Genet. 96:412-417(2000). RN [85] RP VARIANTS GCCR HIS-477 AND SER-679. RX PubMed=11589680; DOI=10.1046/j.1365-2265.2001.01323.x; RA Ruiz M., Lind U., Gaafvels M., Eggertsen G., Carlstedt-Duke J., Nilsson L., RA Holtmann M., Stierna P., Wikstroem A.-C., Werner S.; RT "Characterization of two novel mutations in the glucocorticoid receptor RT gene in patients with primary cortisol resistance."; RL Clin. Endocrinol. (Oxf.) 55:363-371(2001). RN [86] RP VARIANT SER-363. RX PubMed=11344238; DOI=10.1210/jcem.86.5.7465; RA Dobson M.G., Redfern C.P.F., Unwin N., Weaver J.U.; RT "The N363S polymorphism of the glucocorticoid receptor: potential RT contribution to central obesity in men and lack of association with other RT risk factors for coronary heart disease and diabetes mellitus."; RL J. Clin. Endocrinol. Metab. 86:2270-2274(2001). RN [87] RP CHARACTERIZATION OF VARIANT GCCR ASN-559. RX PubMed=11701741; DOI=10.1210/jcem.86.11.8017; RA Kino T., Stauber R.H., Resau J.H., Pavlakis G.N., Chrousos G.P.; RT "Pathologic human GR mutant has a transdominant negative effect on the RT wild-type GR by inhibiting its translocation into the nucleus: importance RT of the ligand-binding domain for intracellular GR trafficking."; RL J. Clin. Endocrinol. Metab. 86:5600-5608(2001). RN [88] RP VARIANT LYS-23. RX PubMed=12351458; DOI=10.2337/diabetes.51.10.3128; RA van Rossum E.F.C., Koper J.W., Huizenga N.A.T.M., Uitterlinden A.G., RA Janssen J.A.M.J.L., Brinkmann A.O., Grobbee D.E., de Jong F.H., RA van Duyn C.M., Pols H.A.P., Lamberts S.W.J.; RT "A polymorphism in the glucocorticoid receptor gene, which decreases RT sensitivity to glucocorticoids in vivo, is associated with low insulin and RT cholesterol levels."; RL Diabetes 51:3128-3134(2002). RN [89] RP VARIANT PSEUDOHERMAPHRODITISM ALA-571. RX PubMed=11932321; DOI=10.1210/jcem.87.4.8379; RA Mendonca B.B., Leite M.V., de Castro M., Kino T., Elias L.L.K., RA Bachega T.A.S., Arnhold I.J.P., Chrousos G.P., Latronico A.C.; RT "Female pseudohermaphroditism caused by a novel homozygous missense RT mutation of the GR gene."; RL J. Clin. Endocrinol. Metab. 87:1805-1809(2002). RN [90] RP VARIANT GCCR MET-747, AND ALTERED INTERACTION WITH THE COACTIVATOR NCOA2. RX PubMed=12050230; DOI=10.1210/jcem.87.6.8520; RA Vottero A., Kino T., Combe H., Lecomte P., Chrousos G.P.; RT "A novel, C-terminal dominant negative mutation of the GR causes familial RT glucocorticoid resistance through abnormal interactions with p160 steroid RT receptor coactivators."; RL J. Clin. Endocrinol. Metab. 87:2658-2667(2002). RN [91] RP VARIANT LYS-23. RX PubMed=15276593; DOI=10.1016/j.amjmed.2004.01.027; RA van Rossum E.F.C., Feelders R.A., van den Beld A.W., Uitterlinden A.G., RA Janssen J.A.M.J.L., Ester W., Brinkmann A.O., Grobbee D.E., de Jong F.H., RA Pols H.A.P., Koper J.W., Lamberts S.W.J.; RT "Association of the ER22/23EK polymorphism in the glucocorticoid receptor RT gene with survival and C-reactive protein levels in elderly men."; RL Am. J. Med. 117:158-162(2004). RN [92] RP VARIANT LYS-23. RX PubMed=15292341; DOI=10.1210/jc.2003-031422; RA van Rossum E.F.C., Voorhoeve P.G., te Velde S.J., Koper J.W., RA Delemarre-van de Waal H.A., Kemper H.C.G., Lamberts S.W.J.; RT "The ER22/23EK polymorphism in the glucocorticoid receptor gene is RT associated with a beneficial body composition and muscle strength in young RT adults."; RL J. Clin. Endocrinol. Metab. 89:4004-4009(2004). RN [93] RP VARIANT GCCR PRO-773, CHARACTERIZATION OF VARIANT GCCR PRO-773, INVOLVEMENT RP IN GCCR, FUNCTION (ISOFORM ALPHA), INTERACTION WITH GRIP1, AND SUBCELLULAR RP LOCATION (ISOFORM ALPHA). RX PubMed=15769988; DOI=10.1210/jc.2004-1920; RA Charmandari E., Raji A., Kino T., Ichijo T., Tiulpakov A., Zachman K., RA Chrousos G.P.; RT "A novel point mutation in the ligand-binding domain (LBD) of the human RT glucocorticoid receptor (hGR) causing generalized glucocorticoid RT resistance: the importance of the C terminus of hGR LBD in conferring RT transactivational activity."; RL J. Clin. Endocrinol. Metab. 90:3696-3705(2005). RN [94] RP VARIANTS LYS-23 AND SER-363, AND CHARACTERIZATION OF VARIANTS LYS-23 AND RP SER-363. RX PubMed=16030164; DOI=10.1210/jc.2005-0646; RA Russcher H., Smit P., van den Akker E.L., van Rossum E.F., Brinkmann A.O., RA de Jong F.H., Lamberts S.W., Koper J.W.; RT "Two polymorphisms in the glucocorticoid receptor gene directly affect RT glucocorticoid-regulated gene expression."; RL J. Clin. Endocrinol. Metab. 90:5804-5810(2005). RN [95] RP VARIANT GCCR LEU-737, CHARACTERIZATION OF VARIANT GCCR LEU-737, FUNCTION RP (ISOFORM ALPHA), INTERACTION WITH GRIP1, AND SUBCELLULAR LOCATION (ISOFORM RP ALPHA). RX PubMed=17635946; DOI=10.1210/jc.2006-2830; RA Charmandari E., Kino T., Ichijo T., Jubiz W., Mejia L., Zachman K., RA Chrousos G.P.; RT "A novel point mutation in helix 11 of the ligand-binding domain of the RT human glucocorticoid receptor gene causing generalized glucocorticoid RT resistance."; RL J. Clin. Endocrinol. Metab. 92:3986-3990(2007). RN [96] RP VARIANT GCCR GLN-714, AND CHARACTERIZATION OF VARIANT GCCR GLN-714. RX PubMed=20335448; DOI=10.1210/jc.2009-2463; RA Nader N., Bachrach B.E., Hurt D.E., Gajula S., Pittman A., Lescher R., RA Kino T.; RT "A novel point mutation in helix 10 of the human glucocorticoid receptor RT causes generalized glucocorticoid resistance by disrupting the structure of RT the ligand-binding domain."; RL J. Clin. Endocrinol. Metab. 95:2281-2285(2010). RN [97] RP VARIANT GCCR ILE-556. RX PubMed=21362280; RA Zhu H.J., Dai Y.F., Wang O., Li M., Lu L., Zhao W.G., Xing X.P., Pan H., RA Li N.S., Gong F.Y.; RT "Generalized glucocorticoid resistance accompanied with an adrenocortical RT adenoma and caused by a novel point mutation of human glucocorticoid RT receptor gene."; RL Chin. Med. J. 124:551-555(2011). RN [98] RP CHARACTERIZATION OF VARIANT GCCR ALA-423. RX PubMed=23426617; DOI=10.1210/jc.2012-3549; RA Roberts M.L., Kino T., Nicolaides N.C., Hurt D.E., Katsantoni E., RA Sertedaki A., Komianou F., Kassiou K., Chrousos G.P., Charmandari E.; RT "A novel point mutation in the DNA-binding domain (DBD) of the human RT glucocorticoid receptor causes primary generalized glucocorticoid RT resistance by disrupting the hydrophobic structure of its DBD."; RL J. Clin. Endocrinol. Metab. 98:E790-E795(2013). RN [99] RP VARIANT GCCR GLY-575, AND CHARACTERIZATION OF VARIANT GCCR GLY-575. RX PubMed=24483153; DOI=10.1210/jc.2013-3005; RA Nicolaides N.C., Roberts M.L., Kino T., Braatvedt G., Hurt D.E., RA Katsantoni E., Sertedaki A., Chrousos G.P., Charmandari E.; RT "A novel point mutation of the human glucocorticoid receptor gene causes RT primary generalized glucocorticoid resistance through impaired interaction RT with the LXXLL motif of the p160 coactivators: dissociation of the RT transactivating and transreppressive activities."; RL J. Clin. Endocrinol. Metab. 99:E902-E907(2014). RN [100] RP VARIANT GCCR ARG-726, AND CHARACTERIZATION OF VARIANT GCCR ARG-726. RX PubMed=26031419; DOI=10.1111/eci.12470; RA Nicolaides N.C., Geer E.B., Vlachakis D., Roberts M.L., Psarra A.M., RA Moutsatsou P., Sertedaki A., Kossida S., Charmandari E.; RT "A novel mutation of the hGR gene causing Chrousos syndrome."; RL Eur. J. Clin. Invest. 45:782-791(2015). RN [101] RP CHARACTERIZATION OF VARIANT GCCR ILE-556. RX PubMed=26541474; DOI=10.1111/eci.12563; RA Nicolaides N.C., Skyrla E., Vlachakis D., Psarra A.M., Moutsatsou P., RA Sertedaki A., Kossida S., Charmandari E.; RT "Functional characterization of the hGRalphaT556I causing Chrousos RT syndrome."; RL Eur. J. Clin. Invest. 46:42-49(2016). RN [102] RP VARIANTS GCCR SER-477; CYS-478 AND PRO-672, CHARACTERIZATION OF VARIANTS RP GCCR SER-477; CYS-478 AND CYS-478, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27120390; DOI=10.1002/humu.23008; RA Vitellius G., Fagart J., Delemer B., Amazit L., Ramos N., Bouligand J., RA Le Billan F., Castinetti F., Guiochon-Mantel A., Trabado S., Lombes M.; RT "Three novel heterozygous point mutations of NR3C1 causing glucocorticoid RT resistance."; RL Hum. Mutat. 37:794-803(2016). CC -!- FUNCTION: Receptor for glucocorticoids (GC) (PubMed:27120390). Has a CC dual mode of action: as a transcription factor that binds to CC glucocorticoid response elements (GRE), both for nuclear and CC mitochondrial DNA, and as a modulator of other transcription factors CC (PubMed:28139699). Affects inflammatory responses, cellular CC proliferation and differentiation in target tissues. Involved in CC chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA CC degradation by binding to the 5' UTR of target mRNAs and interacting CC with PNRC2 in a ligand-dependent manner which recruits the RNA helicase CC UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay CC (PubMed:25775514). Could act as a coactivator for STAT5-dependent CC transcription upon growth hormone (GH) stimulation and could reveal an CC essential role of hepatic GR in the control of body growth (By CC similarity). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27120390, CC ECO:0000269|PubMed:28139699, ECO:0000269|PubMed:9590696}. CC -!- FUNCTION: [Isoform Alpha]: Has transcriptional activation and CC repression activity (PubMed:15866175, PubMed:19248771, PubMed:20484466, CC PubMed:23820903, PubMed:11435610, PubMed:15769988, PubMed:17635946, CC PubMed:19141540, PubMed:21664385). Mediates glucocorticoid-induced CC apoptosis (PubMed:23303127). Promotes accurate chromosome segregation CC during mitosis (PubMed:25847991). May act as a tumor suppressor CC (PubMed:25847991). May play a negative role in adipogenesis through the CC regulation of lipolytic and antilipogenic gene expression (By CC similarity). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:15866175, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:19248771, CC ECO:0000269|PubMed:20484466, ECO:0000269|PubMed:21664385, CC ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903, CC ECO:0000269|PubMed:25847991}. CC -!- FUNCTION: [Isoform Beta]: Acts as a dominant negative inhibitor of CC isoform Alpha (PubMed:7769088, PubMed:8621628, PubMed:20484466). Has CC intrinsic transcriptional activity independent of isoform Alpha when CC both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses CC this transcription modulator function on its own (PubMed:20484466). Has CC no hormone-binding activity (PubMed:8621628). May play a role in CC controlling glucose metabolism by maintaining insulin sensitivity (By CC similarity). Reduces hepatic gluconeogenesis through down-regulation of CC PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly CC regulates STAT1 expression in isoform Alpha-independent manner CC (PubMed:26711253). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:20484466, CC ECO:0000269|PubMed:26711253, ECO:0000269|PubMed:7769088, CC ECO:0000269|PubMed:8621628}. CC -!- FUNCTION: [Isoform Alpha-2]: Has lower transcriptional activation CC activity than isoform Alpha. Exerts a dominant negative effect on CC isoform Alpha trans-repression mechanism (PubMed:20484466). CC -!- FUNCTION: [Isoform GR-P]: Increases activity of isoform Alpha. CC {ECO:0000269|PubMed:11358809}. CC -!- FUNCTION: [Isoform Alpha-B]: More effective than isoform Alpha in CC transcriptional activation, but not repression activity. CC {ECO:0000269|PubMed:11435610, ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform 10]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:20484466}. CC -!- FUNCTION: [Isoform Alpha-C1]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-C2]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-C3]: Has highest transcriptional activation CC activity of all isoforms created by alternative initiation CC (PubMed:15866175, PubMed:23820903). Has transcriptional repression CC activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis CC (PubMed:23303127, PubMed:23820903). {ECO:0000269|PubMed:15866175, CC ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}. CC -!- FUNCTION: [Isoform Alpha-D1]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-D2]: Has transcriptional activation activity. CC {ECO:0000269|PubMed:15866175}. CC -!- FUNCTION: [Isoform Alpha-D3]: Has lowest transcriptional activation CC activity of all isoforms created by alternative initiation CC (PubMed:15866175, PubMed:23820903). Has transcriptional repression CC activity (PubMed:23303127). {ECO:0000269|PubMed:15866175, CC ECO:0000269|PubMed:23303127, ECO:0000269|PubMed:23820903}. CC -!- SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90AA1, CC HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, CC or the immunophilin homolog PPP5C (PubMed:21730050). Upon ligand CC binding FKBP5 dissociates from the complex and FKBP4 takes its place, CC thereby linking the complex to dynein and mediating transport to the CC nucleus, where the complex dissociates (By similarity). Probably forms CC a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, CC PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this CC complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 CC (PubMed:29127155). Directly interacts with UNC45A (PubMed:16478993). CC Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the CC retinoid X receptor. Binds STAT5A and STAT5B homodimers and CC heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 and CC TRIM28 (By similarity). Interacts with several coactivator complexes, CC including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and CC p160 coactivators such as NCOA2 and NCOA6 (PubMed:10866662, CC PubMed:12151000, PubMed:12686538, PubMed:9154805, PubMed:9590696). CC Interaction with BAG1 inhibits transactivation (PubMed:10477749). CC Interacts with HEXIM1 and TGFB1I1 (PubMed:12415108, PubMed:15211577, CC PubMed:15941832). Interacts with NCOA1 (PubMed:9590696). Interacts with CC NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). CC Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion CC (PubMed:19141540, PubMed:21980503, PubMed:22170608). Interacts with CC CIART (By similarity). Interacts with RWDD3 (By similarity). Interacts CC with UBE2I/UBC9 and this interaction is enhanced in the presence of CC RWDD3 (By similarity). Interacts with GRIP1 (PubMed:15769988, CC PubMed:17635946). Interacts with NR4A3 (via nuclear receptor DNA- CC binding domain), represses transcription activity of NR4A3 on the POMC CC promoter Nur response element (NurRE) (PubMed:15591535). Directly CC interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; CC the interaction leads to rapid mRNA degradation (PubMed:25775514). CC Interacts with GSK3B (PubMed:18838540). Interacts with FNIP1 and FNIP2 CC (PubMed:27353360). Interacts (via C-terminus) with HNRNPU (via C- CC terminus) (PubMed:9353307). Interacts with MCM3AP (PubMed:16914116). CC Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By CC similarity). In the absence of hormonal ligand, interacts with TACC1 CC (PubMed:20078863). Interacts (via NR LBD domain) with ZNF764 (via KRAB CC domain); the interaction regulates transcription factor activity of CC NR3C1 by directing its actions toward certain biologic pathways CC (PubMed:28139699). {ECO:0000250|UniProtKB:P06536, CC ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:10477749, CC ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:12151000, CC ECO:0000269|PubMed:12686538, ECO:0000269|PubMed:15211577, CC ECO:0000269|PubMed:15591535, ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:15941832, ECO:0000269|PubMed:16478993, CC ECO:0000269|PubMed:16914116, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:18838540, ECO:0000269|PubMed:19141540, CC ECO:0000269|PubMed:20078863, ECO:0000269|PubMed:21730050, CC ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22170608, CC ECO:0000269|PubMed:25775514, ECO:0000269|PubMed:27353360, CC ECO:0000269|PubMed:28139699, ECO:0000269|PubMed:29127155, CC ECO:0000269|PubMed:9154805, ECO:0000269|PubMed:9353307, CC ECO:0000269|PubMed:9590696}. CC -!- INTERACTION: CC P04150; P31749: AKT1; NbExp=5; IntAct=EBI-493507, EBI-296087; CC P04150; P01730: CD4; NbExp=2; IntAct=EBI-493507, EBI-353826; CC P04150; P00533: EGFR; NbExp=3; IntAct=EBI-493507, EBI-297353; CC P04150; P41235: HNF4A; NbExp=2; IntAct=EBI-493507, EBI-1049011; CC P04150; P07900: HSP90AA1; NbExp=8; IntAct=EBI-493507, EBI-296047; CC P04150; Q6ZU52: KIAA0408; NbExp=2; IntAct=EBI-493507, EBI-739493; CC P04150; P06239: LCK; NbExp=3; IntAct=EBI-493507, EBI-1348; CC P04150; P28702: RXRB; NbExp=4; IntAct=EBI-493507, EBI-748576; CC P04150; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-493507, EBI-745901; CC P04150; O95416: SOX14; NbExp=3; IntAct=EBI-493507, EBI-9087806; CC P04150; P82094: TMF1; NbExp=3; IntAct=EBI-493507, EBI-949763; CC P04150; P59598: Asxl1; Xeno; NbExp=2; IntAct=EBI-493507, EBI-5743705; CC P04150; Q62667: Mvp; Xeno; NbExp=2; IntAct=EBI-493507, EBI-918333; CC P04150-1; Q61026: Ncoa2; Xeno; NbExp=3; IntAct=EBI-15750116, EBI-688662; CC -!- SUBCELLULAR LOCATION: [Isoform Alpha]: Cytoplasm CC {ECO:0000269|PubMed:15769988, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:18838540, ECO:0000269|PubMed:27120390, CC ECO:0000269|PubMed:8621628}. Nucleus {ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:17635946, ECO:0000269|PubMed:18838540, CC ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:8621628}. Mitochondrion CC {ECO:0000269|PubMed:21664385}. Cytoplasm, cytoskeleton, spindle CC {ECO:0000269|PubMed:25847991}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:25847991}. Note=After CC ligand activation, translocates from the cytoplasm to the nucleus. In CC the presence of NR1D1 shows a time-dependent subcellular localization, CC localizing to the cytoplasm at ZT8 and to the nucleus at ZT20 (By CC similarity). Lacks this diurnal pattern of localization in the absence CC of NR1D1, localizing to both nucleus and the cytoplasm at ZT8 and ZT20 CC (By similarity). {ECO:0000250|UniProtKB:P06537, CC ECO:0000269|PubMed:18838540, ECO:0000269|PubMed:27120390, CC ECO:0000269|PubMed:8621628}. CC -!- SUBCELLULAR LOCATION: [Isoform Beta]: Nucleus CC {ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:26711253, CC ECO:0000269|PubMed:8621628}. Cytoplasm {ECO:0000269|PubMed:19248771, CC ECO:0000269|PubMed:26711253}. Note=Expressed predominantly in the CC nucleus with some expression also detected in the cytoplasm. CC {ECO:0000269|PubMed:19248771, ECO:0000269|PubMed:26711253}. CC -!- SUBCELLULAR LOCATION: [Isoform Alpha-B]: Nucleus CC {ECO:0000269|PubMed:15866175}. Cytoplasm {ECO:0000269|PubMed:15866175}. CC Note=After ligand activation, translocates from the cytoplasm to the CC nucleus. {ECO:0000269|PubMed:15866175}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=16; CC Name=Alpha; Synonyms=Alpha-A, GR-alphaA; CC IsoId=P04150-1; Sequence=Displayed; CC Name=Beta; Synonyms=Beta-A; CC IsoId=P04150-2; Sequence=VSP_003703; CC Name=Alpha-2; Synonyms=Gamma; CC IsoId=P04150-3; Sequence=VSP_007363; CC Name=Beta-2; CC IsoId=P04150-6; Sequence=VSP_007363, VSP_003703; CC Name=GR-A alpha; CC IsoId=P04150-5; Sequence=VSP_013340; CC Name=GR-A beta; CC IsoId=P04150-7; Sequence=VSP_013340, VSP_003703; CC Name=GR-P; CC IsoId=P04150-4; Sequence=Not described; CC Name=Alpha-B; Synonyms=GR-alphaB; CC IsoId=P04150-8; Sequence=VSP_018773; CC Name=Beta-B; CC IsoId=P04150-9; Sequence=VSP_018773, VSP_003703; CC Name=10; Synonyms=hGRDelta313-338; CC IsoId=P04150-10; Sequence=VSP_043908; CC Name=Alpha-C1; Synonyms=GR-alphaC1; CC IsoId=P04150-11; Sequence=VSP_058317; CC Name=Alpha-C2; Synonyms=GR-alphaC2; CC IsoId=P04150-12; Sequence=VSP_058316; CC Name=Alpha-C3; Synonyms=GR-alphaC3; CC IsoId=P04150-13; Sequence=VSP_058315; CC Name=Alpha-D1; Synonyms=GR-alphaD1; CC IsoId=P04150-14; Sequence=VSP_058314; CC Name=Alpha-D2; Synonyms=GR-alphaD2; CC IsoId=P04150-15; Sequence=VSP_058313; CC Name=Alpha-D3; Synonyms=GR-alphaD3; CC IsoId=P04150-16; Sequence=VSP_058312; CC -!- TISSUE SPECIFICITY: Widely expressed including bone, stomach, lung, CC liver, colon, breast, ovary, pancreas and kidney (PubMed:25847991). In CC the heart, detected in left and right atria, left and right ventricles, CC aorta, apex, intraventricular septum, and atrioventricular node as well CC as whole adult and fetal heart (PubMed:10902803). CC {ECO:0000269|PubMed:10902803, ECO:0000269|PubMed:25847991}. CC -!- TISSUE SPECIFICITY: [Isoform Beta]: Widely expressed including brain, CC bone marrow, thymus, spleen, liver, kidney, pancreas, lung, fat, CC skeletal muscle, heart, placenta and blood leukocytes. CC {ECO:0000269|PubMed:7769088, ECO:0000269|PubMed:8621628}. CC -!- TISSUE SPECIFICITY: [Isoform Alpha-2]: Widely expressed. CC {ECO:0000269|PubMed:10566686}. CC -!- INDUCTION: [Isoform Alpha]: Induced by TNF (at protein level). CC {ECO:0000269|PubMed:11381138}. CC -!- INDUCTION: [Isoform Beta]: Induced by TNF and becomes the predominant CC isoform which may lead to glucocorticoid resistance (at protein level). CC {ECO:0000269|PubMed:11381138}. CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a CC DNA-binding domain and a C-terminal ligand-binding domain CC (PubMed:3841189). The ligand-binding domain is required for correct CC chromosome segregation during mitosis although ligand binding is not CC required (PubMed:25847991). {ECO:0000269|PubMed:25847991, CC ECO:0000269|PubMed:3841189}. CC -!- PTM: Acetylation by CLOCK reduces its binding to glucocorticoid CC response elements and its transcriptional activity. CC {ECO:0000269|PubMed:19141540, ECO:0000269|PubMed:21980503}. CC -!- PTM: Increased proteasome-mediated degradation in response to CC glucocorticoids (PubMed:11555652). Isoform Alpha-B appears to be more CC susceptible to proteolytic degradation than isoform Alpha CC (PubMed:11435610). {ECO:0000269|PubMed:11435610, CC ECO:0000269|PubMed:11555652}. CC -!- PTM: Phosphorylated in the absence of hormone; becomes CC hyperphosphorylated in the presence of glucocorticoid. The Ser-203, CC Ser-226 and Ser-404-phosphorylated forms are mainly cytoplasmic, and CC the Ser-211-phosphorylated form is nuclear (PubMed:12000743, CC PubMed:18838540). Phosphorylation at Ser-211 increases transcriptional CC activity (PubMed:12000743, PubMed:18483179). Phosphorylation at Ser- CC 203, Ser-226 and Ser-404 decreases signaling capacity (PubMed:12000743, CC PubMed:18483179, PubMed:18838540). Phosphorylation at Ser-404 may CC protect from glucocorticoid-induced apoptosis (PubMed:18838540). CC Phosphorylation at Ser-203 and Ser-211 is not required in regulation of CC chromosome segregation (PubMed:25847991). May be dephosphorylated by CC PPP5C, attenuates NR3C1 action (By similarity). CC {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:12000743, CC ECO:0000269|PubMed:18483179, ECO:0000269|PubMed:18838540, CC ECO:0000269|PubMed:25847991}. CC -!- PTM: Sumoylation at Lys-277 and Lys-293 negatively regulates its CC transcriptional activity (PubMed:12144530). Sumoylation at Lys-703 CC positively regulates its transcriptional activity in the presence of CC RWDD3 (By similarity). Sumoylation at Lys-277 and Lys-293 is CC dispensable whereas sumoylation at Lys-703 is critical for the CC stimulatory effect of RWDD3 on its transcriptional activity (By CC similarity). Heat shock increases sumoylation in a RWDD3-dependent CC manner (By similarity). {ECO:0000250|UniProtKB:P06536, CC ECO:0000269|PubMed:12144530}. CC -!- PTM: Ubiquitinated; restricts glucocorticoid-mediated transcriptional CC signaling. {ECO:0000250|UniProtKB:P06537}. CC -!- POLYMORPHISM: Carriers of the 22-Glu-Lys-23 allele are relatively more CC resistant to the effects of GCs with respect to the sensitivity of the CC adrenal feedback mechanism than non-carriers, resulting in a better CC metabolic health profile. Carriers have a better survival than non- CC carriers, as well as lower serum CRP levels. The 22-Glu-Lys-23 CC polymorphism is associated with a sex-specific, beneficial body CC composition at young-adult age, as well as greater muscle strength in CC males. CC -!- DISEASE: Glucocorticoid resistance, generalized (GCCR) [MIM:615962]: An CC autosomal dominant disease characterized by increased plasma cortisol CC concentration and high urinary free cortisol, resistance to adrenal CC suppression by dexamethasone, and the absence of Cushing syndrome CC typical signs. Clinical features include hypoglycemia, hypertension, CC metabolic alkalosis, chronic fatigue and profound anxiety. CC {ECO:0000269|PubMed:11589680, ECO:0000269|PubMed:11701741, CC ECO:0000269|PubMed:12050230, ECO:0000269|PubMed:15769988, CC ECO:0000269|PubMed:1704018, ECO:0000269|PubMed:17635946, CC ECO:0000269|PubMed:20335448, ECO:0000269|PubMed:21362280, CC ECO:0000269|PubMed:23426617, ECO:0000269|PubMed:24483153, CC ECO:0000269|PubMed:26031419, ECO:0000269|PubMed:26541474, CC ECO:0000269|PubMed:27120390, ECO:0000269|PubMed:7683692}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform Beta]: High constitutive expression by CC neutrophils may provide a mechanism by which these cells escape CC glucocorticoid-induced cell death and up-regulation by pro-inflammatory CC cytokines such as IL8 further enhances their survival in the presence CC of glucocorticoids during inflammation. {ECO:0000269|PubMed:11238589}. CC -!- MISCELLANEOUS: Can up- or down-modulate aggregation and nuclear CC localization of expanded polyglutamine polypeptides derived from AR and CC HD through specific regulation of gene expression. Aggregation and CC nuclear localization of expanded polyglutamine proteins are regulated CC cellular processes that can be modulated by this receptor, a well- CC characterized transcriptional regulator. {ECO:0000269|PubMed:10639135}. CC -!- MISCELLANEOUS: [Isoform Alpha]: Predominant physiological form. CC {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-2]: Due to a partial intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform Beta-2]: Due to a partial intron retention. CC {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform GR-A alpha]: Lacks exons 5, 6 and 7. Found in CC glucocorticoid-resistant myeloma patients. CC {ECO:0000269|PubMed:8358712}. CC -!- MISCELLANEOUS: [Isoform GR-A beta]: Lacks exons 5, 6 and 7. CC {ECO:0000269|PubMed:8358712}. CC -!- MISCELLANEOUS: [Isoform GR-P]: Encoded by exons 2-7 plus several CC basepairs from the subsequent intron region. Lacks the ligand binding CC domain. Accounts for up to 10-20% of mRNAs. CC {ECO:0000269|PubMed:8358712}. CC -!- MISCELLANEOUS: [Isoform Alpha-B]: Produced by alternative initiation at CC Met-27 of isoform Alpha. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform Beta-B]: Produced by alternative initiation at CC Met-27 of isoform Beta. {ECO:0000269|PubMed:15866175, ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform Alpha-C1]: Produced by alternative initiation CC at Met-86 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-C2]: Produced by alternative initiation CC at Met-90 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-C3]: Produced by alternative initiation CC at Met-98 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-D1]: Produced by alternative initiation CC at Met-316 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-D2]: Produced by alternative initiation CC at Met-331 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- MISCELLANEOUS: [Isoform Alpha-D3]: Produced by alternative initiation CC at Met-336 of isoform Alpha. {ECO:0000269|PubMed:15866175}. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. {ECO:0000305}. CC -!- CAUTION: Had previously been shown to interact with PELP1. However this CC paper was retracted as cell-based data was viewed as unreliable. CC {ECO:0000305|PubMed:12415108, ECO:0000305|PubMed:19666546}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/nr3c1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glucocorticoid receptor entry; CC URL="https://en.wikipedia.org/wiki/Glucocorticoid_receptor"; 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; X03225; CAA26976.1; -; mRNA. DR EMBL; X03348; CAA27054.1; -; mRNA. DR EMBL; AH005496; AAB64353.1; -; Genomic_DNA. DR EMBL; AH005496; AAB64354.1; -; Genomic_DNA. DR EMBL; HQ205546; ADP91135.1; -; Genomic_DNA. DR EMBL; HQ205547; ADP91138.1; -; Genomic_DNA. DR EMBL; HQ205548; ADP91141.1; -; Genomic_DNA. DR EMBL; HQ205549; ADP91144.1; -; Genomic_DNA. DR EMBL; HQ205550; ADP91147.1; -; Genomic_DNA. DR EMBL; HQ205551; ADP91150.1; -; Genomic_DNA. DR EMBL; HQ205552; ADP91153.1; -; Genomic_DNA. DR EMBL; HQ205553; ADP91156.1; -; Genomic_DNA. DR EMBL; HQ205554; ADP91159.1; -; Genomic_DNA. DR EMBL; HQ205555; ADP91162.1; -; Genomic_DNA. DR EMBL; HQ205556; ADP91165.1; -; Genomic_DNA. DR EMBL; HQ205557; ADP91168.1; -; Genomic_DNA. DR EMBL; HQ205558; ADP91171.1; -; Genomic_DNA. DR EMBL; HQ205559; ADP91174.1; -; Genomic_DNA. DR EMBL; HQ205560; ADP91177.1; -; Genomic_DNA. DR EMBL; HQ205561; ADP91180.1; -; Genomic_DNA. DR EMBL; HQ205562; ADP91183.1; -; Genomic_DNA. DR EMBL; HQ205563; ADP91186.1; -; Genomic_DNA. DR EMBL; HQ205564; ADP91189.1; -; Genomic_DNA. DR EMBL; HQ205565; ADP91192.1; -; Genomic_DNA. DR EMBL; HQ205566; ADP91195.1; -; Genomic_DNA. DR EMBL; HQ205567; ADP91198.1; -; Genomic_DNA. DR EMBL; HQ205568; ADP91201.1; -; Genomic_DNA. DR EMBL; HQ205569; ADP91204.1; -; Genomic_DNA. DR EMBL; HQ205570; ADP91207.1; -; Genomic_DNA. DR EMBL; HQ205571; ADP91210.1; -; Genomic_DNA. DR EMBL; HQ205572; ADP91213.1; -; Genomic_DNA. DR EMBL; HQ205573; ADP91216.1; -; Genomic_DNA. DR EMBL; HQ205574; ADP91219.1; -; Genomic_DNA. DR EMBL; HQ205575; ADP91222.1; -; Genomic_DNA. DR EMBL; HQ205576; ADP91225.1; -; Genomic_DNA. DR EMBL; HQ205577; ADP91228.1; -; Genomic_DNA. DR EMBL; HQ205578; ADP91231.1; -; Genomic_DNA. DR EMBL; HQ205579; ADP91234.1; -; Genomic_DNA. DR EMBL; HQ205580; ADP91237.1; -; Genomic_DNA. DR EMBL; HQ205581; ADP91240.1; -; Genomic_DNA. DR EMBL; HQ205582; ADP91243.1; -; Genomic_DNA. DR EMBL; HQ205583; ADP91246.1; -; Genomic_DNA. DR EMBL; HQ205584; ADP91249.1; -; Genomic_DNA. DR EMBL; HQ205585; ADP91252.1; -; Genomic_DNA. DR EMBL; AM183262; CAJ65924.1; -; mRNA. DR EMBL; HQ450643; AED99114.1; -; mRNA. DR EMBL; U01351; AAA16603.1; -; mRNA. DR EMBL; AK223594; BAD97314.1; -; mRNA. DR EMBL; BX640610; CAE45716.1; -; mRNA. DR EMBL; AY436590; AAQ97180.1; -; Genomic_DNA. DR EMBL; EU332858; ABY87547.1; -; Genomic_DNA. DR EMBL; AC005601; AAC34207.1; -; Genomic_DNA. DR EMBL; AC004782; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091925; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW61872.1; -; Genomic_DNA. DR EMBL; CH471062; EAW61873.1; -; Genomic_DNA. DR EMBL; BC015610; AAH15610.1; -; mRNA. DR EMBL; M69104; AAA88049.1; -; Genomic_DNA. DR EMBL; AH002750; AAA53151.1; -; Genomic_DNA. DR EMBL; S68378; AAB20466.1; -; Genomic_DNA. DR CCDS; CCDS34258.1; -. [P04150-3] DR CCDS; CCDS4278.1; -. [P04150-1] DR CCDS; CCDS47298.1; -. [P04150-2] DR PIR; A93370; QRHUGA. DR PIR; B93370; QRHUGB. DR RefSeq; NP_000167.1; NM_000176.2. [P04150-1] DR RefSeq; NP_001018084.1; NM_001018074.1. [P04150-1] DR RefSeq; NP_001018085.1; NM_001018075.1. [P04150-1] DR RefSeq; NP_001018086.1; NM_001018076.1. [P04150-1] DR RefSeq; NP_001018087.1; NM_001018077.1. [P04150-1] DR RefSeq; NP_001018661.1; NM_001020825.1. [P04150-2] DR RefSeq; NP_001019265.1; NM_001024094.1. [P04150-3] DR RefSeq; NP_001191187.1; NM_001204258.1. [P04150-8] DR RefSeq; NP_001191188.1; NM_001204259.1. [P04150-11] DR RefSeq; NP_001191189.1; NM_001204260.1. [P04150-12] DR RefSeq; NP_001191190.1; NM_001204261.1. [P04150-13] DR RefSeq; NP_001191191.1; NM_001204262.1. [P04150-14] DR RefSeq; NP_001191192.1; NM_001204263.1. [P04150-15] DR RefSeq; NP_001191193.1; NM_001204264.1. [P04150-16] DR RefSeq; XP_005268476.1; XM_005268419.3. DR RefSeq; XP_005268477.1; XM_005268420.4. DR RefSeq; XP_005268479.1; XM_005268422.3. DR RefSeq; XP_005268480.1; XM_005268423.3. DR RefSeq; XP_016864886.1; XM_017009397.1. DR RefSeq; XP_016864887.1; XM_017009398.1. DR PDB; 1M2Z; X-ray; 2.50 A; A/D=521-777. DR PDB; 1NHZ; X-ray; 2.30 A; A=500-777. DR PDB; 1P93; X-ray; 2.70 A; A/B/C/D=500-777. DR PDB; 3BQD; X-ray; 2.50 A; A=525-777. DR PDB; 3CLD; X-ray; 2.84 A; A/B=521-777. DR PDB; 3E7C; X-ray; 2.15 A; A/B=521-777. DR PDB; 3H52; X-ray; 2.80 A; A/B/C/D=528-777. DR PDB; 3K22; X-ray; 2.10 A; A/B=521-777. DR PDB; 3K23; X-ray; 3.00 A; A/B/C=521-777. DR PDB; 4CSJ; X-ray; 2.30 A; A=500-777. DR PDB; 4HN5; X-ray; 1.90 A; A/B=417-506. DR PDB; 4HN6; X-ray; 2.55 A; A/B=417-506. DR PDB; 4LSJ; X-ray; 2.35 A; A=522-777. DR PDB; 4MDD; X-ray; 2.40 A; A/B=522-777. DR PDB; 4P6W; X-ray; 1.95 A; A=526-777. DR PDB; 4P6X; X-ray; 2.50 A; A/C/E/G/I/K=523-777. DR PDB; 4UDC; X-ray; 2.50 A; A=500-777. DR PDB; 4UDD; X-ray; 1.80 A; A=500-777. DR PDB; 5CBX; X-ray; 2.00 A; A/B/E/F=415-495. DR PDB; 5CBY; X-ray; 2.00 A; A/B=415-495. DR PDB; 5CBZ; X-ray; 2.20 A; A/B/E/F=419-495. DR PDB; 5CC1; X-ray; 2.30 A; A/B/W/X=417-506. DR PDB; 5E69; X-ray; 1.85 A; A/B=417-506. DR PDB; 5E6A; X-ray; 2.20 A; A/B=417-506. DR PDB; 5E6B; X-ray; 2.25 A; A/B=417-506. DR PDB; 5E6C; X-ray; 2.20 A; A/B=417-506. DR PDB; 5E6D; X-ray; 2.40 A; A/B=417-506. DR PDB; 5EMC; X-ray; 2.30 A; A/B=411-500. DR PDB; 5EMP; X-ray; 2.30 A; A/B=411-500. DR PDB; 5EMQ; X-ray; 2.30 A; A/B=411-500. DR PDB; 5G3J; X-ray; 2.40 A; A=500-777. DR PDB; 5G5W; X-ray; 2.20 A; A=500-777. DR PDB; 5NFP; X-ray; 2.10 A; A=500-777. DR PDB; 5NFT; X-ray; 2.30 A; A=500-777. DR PDB; 5UC1; X-ray; 2.35 A; A/B=522-549. DR PDB; 5UC3; X-ray; 2.01 A; A/B=522-777. DR PDB; 5VA0; X-ray; 2.29 A; A/B=419-490. DR PDB; 5VA7; X-ray; 2.15 A; A/B=419-488. DR PDB; 6BQU; X-ray; 2.50 A; A/B=421-490. DR PDB; 6CFN; X-ray; 2.50 A; A/B/C/D/E/F/G/H=418-506. DR PDB; 6DXK; X-ray; 3.05 A; A/B=522-777. DR PDB; 6EL6; X-ray; 2.40 A; A=500-777. DR PDB; 6EL7; X-ray; 2.18 A; A=500-777. DR PDB; 6EL9; X-ray; 2.19 A; A=500-777. DR PDB; 6X6D; X-ray; 2.48 A; A/B=417-490. DR PDB; 6X6E; X-ray; 2.00 A; A/B=417-491. DR PDB; 6YMO; X-ray; 2.02 A; C/D=611-623. DR PDB; 6YO8; X-ray; 2.09 A; E/F/G/H=518-530. DR PDB; 6YOS; X-ray; 2.75 A; C=518-530, C=611-623. DR PDB; 7KRJ; EM; 2.56 A; D=520-777. DR PDB; 7KW7; EM; 3.57 A; F=1-777. DR PDB; 7PRV; X-ray; 2.70 A; A/B=385-777. DR PDB; 7PRW; X-ray; 2.50 A; A/B=385-777. DR PDB; 7PRX; X-ray; 2.20 A; A=529-777. DR PDB; 8A9G; X-ray; 1.96 A; C/D=518-530. DR PDB; 8FFV; EM; 3.01 A; C=418-777. DR PDB; 8FFW; EM; 3.23 A; C=418-777. DR PDBsum; 1M2Z; -. DR PDBsum; 1NHZ; -. DR PDBsum; 1P93; -. DR PDBsum; 3BQD; -. DR PDBsum; 3CLD; -. DR PDBsum; 3E7C; -. DR PDBsum; 3H52; -. DR PDBsum; 3K22; -. DR PDBsum; 3K23; -. DR PDBsum; 4CSJ; -. DR PDBsum; 4HN5; -. DR PDBsum; 4HN6; -. DR PDBsum; 4LSJ; -. DR PDBsum; 4MDD; -. DR PDBsum; 4P6W; -. DR PDBsum; 4P6X; -. DR PDBsum; 4UDC; -. DR PDBsum; 4UDD; -. DR PDBsum; 5CBX; -. DR PDBsum; 5CBY; -. DR PDBsum; 5CBZ; -. DR PDBsum; 5CC1; -. DR PDBsum; 5E69; -. DR PDBsum; 5E6A; -. DR PDBsum; 5E6B; -. DR PDBsum; 5E6C; -. DR PDBsum; 5E6D; -. DR PDBsum; 5EMC; -. DR PDBsum; 5EMP; -. DR PDBsum; 5EMQ; -. DR PDBsum; 5G3J; -. DR PDBsum; 5G5W; -. DR PDBsum; 5NFP; -. DR PDBsum; 5NFT; -. DR PDBsum; 5UC1; -. DR PDBsum; 5UC3; -. DR PDBsum; 5VA0; -. DR PDBsum; 5VA7; -. DR PDBsum; 6BQU; -. DR PDBsum; 6CFN; -. DR PDBsum; 6DXK; -. DR PDBsum; 6EL6; -. DR PDBsum; 6EL7; -. DR PDBsum; 6EL9; -. DR PDBsum; 6X6D; -. DR PDBsum; 6X6E; -. DR PDBsum; 6YMO; -. DR PDBsum; 6YO8; -. DR PDBsum; 6YOS; -. DR PDBsum; 7KRJ; -. DR PDBsum; 7KW7; -. DR PDBsum; 7PRV; -. DR PDBsum; 7PRW; -. DR PDBsum; 7PRX; -. DR PDBsum; 8A9G; -. DR PDBsum; 8FFV; -. DR PDBsum; 8FFW; -. DR AlphaFoldDB; P04150; -. DR EMDB; EMD-23004; -. DR EMDB; EMD-23050; -. DR EMDB; EMD-29068; -. DR EMDB; EMD-29069; -. DR EMDB; EMD-5981; -. DR SMR; P04150; -. DR BioGRID; 109165; 1499. DR CORUM; P04150; -. DR DIP; DIP-576N; -. DR ELM; P04150; -. DR IntAct; P04150; 92. DR MINT; P04150; -. DR STRING; 9606.ENSP00000231509; -. DR BindingDB; P04150; -. DR ChEMBL; CHEMBL2034; -. DR DrugBank; DB00240; Alclometasone. DR DrugBank; DB04630; Aldosterone. DR DrugBank; DB00288; Amcinonide. DR DrugBank; DB00394; Beclomethasone dipropionate. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB14669; Betamethasone phosphate. DR DrugBank; DB01222; Budesonide. DR DrugBank; DB01410; Ciclesonide. DR DrugBank; DB01013; Clobetasol propionate. DR DrugBank; DB13158; Clobetasone. DR DrugBank; DB00838; Clocortolone. DR DrugBank; DB01380; Cortisone acetate. DR DrugBank; DB13003; Cortivazol. DR DrugBank; DB11921; Deflazacort. DR DrugBank; DB01260; Desonide. DR DrugBank; DB00547; Desoximetasone. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB00223; Diflorasone. DR DrugBank; DB09095; Difluocortolone. DR DrugBank; DB06781; Difluprednate. DR DrugBank; DB01395; Drospirenone. DR DrugBank; DB00687; Fludrocortisone. DR DrugBank; DB00663; Flumethasone. DR DrugBank; DB00180; Flunisolide. DR DrugBank; DB00591; Fluocinolone acetonide. DR DrugBank; DB01047; Fluocinonide. DR DrugBank; DB00324; Fluorometholone. DR DrugBank; DB01185; Fluoxymesterone. DR DrugBank; DB00846; Flurandrenolide. DR DrugBank; DB13867; Fluticasone. DR DrugBank; DB08906; Fluticasone furoate. DR DrugBank; DB00588; Fluticasone propionate. DR DrugBank; DB11619; Gestrinone. DR DrugBank; DB02210; Hexane-1,6-Diol. DR DrugBank; DB00769; Hydrocortamate. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB14538; Hydrocortisone aceponate. DR DrugBank; DB14539; Hydrocortisone acetate. DR DrugBank; DB14540; Hydrocortisone butyrate. DR DrugBank; DB14541; Hydrocortisone cypionate. DR DrugBank; DB14542; Hydrocortisone phosphate. DR DrugBank; DB14543; Hydrocortisone probutate. DR DrugBank; DB14544; Hydrocortisone valerate. DR DrugBank; DB00367; Levonorgestrel. DR DrugBank; DB14596; Loteprednol etabonate. DR DrugBank; DB00253; Medrysone. DR DrugBank; DB00351; Megestrol acetate. DR DrugBank; DB00959; Methylprednisolone. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB00764; Mometasone. DR DrugBank; DB14512; Mometasone furoate. DR DrugBank; DB00717; Norethisterone. DR DrugBank; DB12637; Onapristone. DR DrugBank; DB05423; ORG-34517. DR DrugBank; DB01384; Paramethasone. DR DrugBank; DB01130; Prednicarbate. DR DrugBank; DB00860; Prednisolone. DR DrugBank; DB15566; Prednisolone acetate. DR DrugBank; DB14631; Prednisolone phosphate. DR DrugBank; DB00635; Prednisone. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB00896; Rimexolone. DR DrugBank; DB14583; Segesterone acetate. DR DrugBank; DB00421; Spironolactone. DR DrugBank; DB09091; Tixocortol. DR DrugBank; DB00620; Triamcinolone. DR DrugBank; DB08867; Ulipristal. DR DrugBank; DB00596; Ulobetasol. DR DrugCentral; P04150; -. DR GuidetoPHARMACOLOGY; 625; -. DR GlyCosmos; P04150; 6 sites, 2 glycans. DR GlyGen; P04150; 7 sites, 2 O-linked glycans (7 sites). DR iPTMnet; P04150; -. DR PhosphoSitePlus; P04150; -. DR BioMuta; NR3C1; -. DR DMDM; 121069; -. DR EPD; P04150; -. DR jPOST; P04150; -. DR MassIVE; P04150; -. DR MaxQB; P04150; -. DR PaxDb; 9606-ENSP00000231509; -. DR PeptideAtlas; P04150; -. DR ProteomicsDB; 51657; -. [P04150-1] DR ProteomicsDB; 51658; -. [P04150-10] DR ProteomicsDB; 51659; -. [P04150-2] DR ProteomicsDB; 51660; -. [P04150-3] DR ProteomicsDB; 51661; -. [P04150-5] DR ProteomicsDB; 51662; -. [P04150-6] DR ProteomicsDB; 51663; -. [P04150-7] DR ProteomicsDB; 51664; -. [P04150-8] DR ProteomicsDB; 51665; -. [P04150-9] DR Pumba; P04150; -. DR Antibodypedia; 1329; 1586 antibodies from 44 providers. DR DNASU; 2908; -. DR Ensembl; ENST00000231509.7; ENSP00000231509.3; ENSG00000113580.15. [P04150-3] DR Ensembl; ENST00000343796.6; ENSP00000343205.2; ENSG00000113580.15. [P04150-1] DR Ensembl; ENST00000394464.7; ENSP00000377977.2; ENSG00000113580.15. [P04150-1] DR Ensembl; ENST00000394466.6; ENSP00000377979.2; ENSG00000113580.15. [P04150-3] DR Ensembl; ENST00000415690.6; ENSP00000387672.2; ENSG00000113580.15. [P04150-2] DR Ensembl; ENST00000424646.6; ENSP00000405282.2; ENSG00000113580.15. [P04150-10] DR Ensembl; ENST00000503201.1; ENSP00000427672.1; ENSG00000113580.15. [P04150-1] DR Ensembl; ENST00000504572.5; ENSP00000422518.1; ENSG00000113580.15. [P04150-3] DR GeneID; 2908; -. DR KEGG; hsa:2908; -. DR MANE-Select; ENST00000394464.7; ENSP00000377977.2; NM_000176.3; NP_000167.1. DR UCSC; uc003lmy.4; human. [P04150-1] DR AGR; HGNC:7978; -. DR CTD; 2908; -. DR DisGeNET; 2908; -. DR GeneCards; NR3C1; -. DR HGNC; HGNC:7978; NR3C1. DR HPA; ENSG00000113580; Low tissue specificity. DR MalaCards; NR3C1; -. DR MIM; 138040; gene. DR MIM; 615962; phenotype. DR neXtProt; NX_P04150; -. DR OpenTargets; ENSG00000113580; -. DR Orphanet; 96253; Cushing disease. DR Orphanet; 786; Generalized glucocorticoid resistance syndrome. DR PharmGKB; PA181; -. DR VEuPathDB; HostDB:ENSG00000113580; -. DR eggNOG; KOG3575; Eukaryota. DR GeneTree; ENSGT00940000156385; -. DR HOGENOM; CLU_020317_0_0_1; -. DR InParanoid; P04150; -. DR OMA; GLYMGDT; -. DR OrthoDB; 5305911at2759; -. DR PhylomeDB; P04150; -. DR TreeFam; TF106510; -. DR PathwayCommons; P04150; -. DR Reactome; R-HSA-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR Reactome; R-HSA-400253; Circadian Clock. DR Reactome; R-HSA-4090294; SUMOylation of intracellular receptors. DR Reactome; R-HSA-8849473; PTK6 Expression. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9768777; Regulation of NPAS4 gene transcription. DR SignaLink; P04150; -. DR SIGNOR; P04150; -. DR BioGRID-ORCS; 2908; 13 hits in 1195 CRISPR screens. DR ChiTaRS; NR3C1; human. DR EvolutionaryTrace; P04150; -. DR GeneWiki; Glucocorticoid_receptor; -. DR GenomeRNAi; 2908; -. DR Pharos; P04150; Tclin. DR PRO; PR:P04150; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; P04150; Protein. DR Bgee; ENSG00000113580; Expressed in endothelial cell and 212 other cell types or tissues. DR ExpressionAtlas; P04150; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016020; C:membrane; IEA:Ensembl. DR GO; GO:0005759; C:mitochondrial matrix; TAS:ProtInc. DR GO; GO:0016607; C:nuclear speck; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell. DR GO; GO:0045202; C:synapse; IEA:GOC. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:CAFA. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0034056; F:estrogen response element binding; IBA:GO_Central. DR GO; GO:0051879; F:Hsp90 protein binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0004883; F:nuclear glucocorticoid receptor activity; TAS:ProtInc. DR GO; GO:0004879; F:nuclear receptor activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL. DR GO; GO:0005496; F:steroid binding; IDA:UniProtKB. DR GO; GO:1990239; F:steroid hormone binding; IDA:UniProtKB. DR GO; GO:0017025; F:TBP-class protein binding; IPI:DisProt. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0030325; P:adrenal gland development; IEA:Ensembl. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IMP:CAFA. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IDA:UniProtKB. DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; IDA:UniProtKB. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:CAFA. DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW. DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0008211; P:glucocorticoid metabolic process; IEA:Ensembl. DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central. DR GO; GO:0060603; P:mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0042711; P:maternal behavior; IEA:Ensembl. DR GO; GO:0014004; P:microglia differentiation; IEA:Ensembl. DR GO; GO:0061744; P:motor behavior; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0150076; P:neuroinflammatory response; IEA:Ensembl. DR GO; GO:0051647; P:nucleus localization; IDA:DisProt. DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:ARUK-UCL. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0031946; P:regulation of glucocorticoid biosynthetic process; IEA:Ensembl. DR GO; GO:0006111; P:regulation of gluconeogenesis; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IEA:Ensembl. DR CDD; cd07172; NR_DBD_GR_PR; 1. DR CDD; cd07076; NR_LBD_GR; 1. DR DisProt; DP00030; -. DR Gene3D; 3.30.50.10; Erythroid Transcription Factor GATA-1, subunit A; 1. DR Gene3D; 1.10.565.10; Retinoid X Receptor; 1. DR IDEAL; IID00014; -. DR InterPro; IPR001409; Glcrtcd_rcpt. DR InterPro; IPR035500; NHR-like_dom_sf. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR PANTHER; PTHR48092:SF5; GLUCOCORTICOID RECEPTOR; 1. DR PANTHER; PTHR48092; KNIRPS-RELATED PROTEIN-RELATED; 1. DR Pfam; PF02155; GCR; 1. 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; SSF57716; Glucocorticoid receptor-like (DNA-binding domain); 1. DR SUPFAM; SSF48508; Nuclear receptor ligand-binding domain; 1. DR PROSITE; PS51843; NR_LBD; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. DR Genevisible; P04150; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing; KW Apoptosis; Cell cycle; Cell division; Chromatin regulator; KW Chromosome partition; Cytoplasm; Cytoskeleton; Disease variant; KW DNA-binding; Isopeptide bond; Lipid-binding; Metal-binding; Methylation; KW Mitochondrion; Mitosis; Nucleus; Phosphoprotein; Pseudohermaphroditism; KW Receptor; Reference proteome; RNA-binding; Steroid-binding; Transcription; KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..777 FT /note="Glucocorticoid receptor" FT /id="PRO_0000019937" FT DOMAIN 524..758 FT /note="NR LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189" FT DNA_BIND 418..493 FT /note="Nuclear receptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 421..441 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT ZN_FING 457..476 FT /note="NR C4-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407" FT REGION 1..420 FT /note="Modulating" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 98..115 FT /note="Required for high transcriptional activity of FT isoform Alpha-C3" FT /evidence="ECO:0000269|PubMed:23820903" FT REGION 130..183 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 394..415 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 485..777 FT /note="Interaction with CLOCK" FT REGION 487..523 FT /note="Hinge" FT REGION 532..697 FT /note="Interaction with CRY1" FT /evidence="ECO:0000269|PubMed:22170608" FT COMPBIAS 130..149 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 166..183 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 8 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 23 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P06537" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 113 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06537" FT MOD_RES 134 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 141 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06537" FT MOD_RES 203 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12000743, FT ECO:0000269|PubMed:18483179, ECO:0000269|PubMed:25847991, FT ECO:0007744|PubMed:24275569" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12000743, FT ECO:0000269|PubMed:18483179, ECO:0000269|PubMed:25847991" FT MOD_RES 226 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:18483179, FT ECO:0007744|PubMed:18669648" FT MOD_RES 267 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 404 FT /note="Phosphoserine; by GSK3-beta" FT /evidence="ECO:0000269|PubMed:18838540" FT MOD_RES 480 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT MOD_RES 492 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT MOD_RES 494 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT MOD_RES 495 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:19141540" FT CROSSLNK 258 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 277 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:12144530" FT CROSSLNK 277 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 293 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO); alternate" FT /evidence="ECO:0000269|PubMed:12144530" FT CROSSLNK 293 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25114211" FT CROSSLNK 419 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:P06537" FT CROSSLNK 703 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO)" FT /evidence="ECO:0000269|PubMed:12144530" FT VAR_SEQ 1..335 FT /note="Missing (in isoform Alpha-D3)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058312" FT VAR_SEQ 1..330 FT /note="Missing (in isoform Alpha-D2)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058313" FT VAR_SEQ 1..315 FT /note="Missing (in isoform Alpha-D1)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058314" FT VAR_SEQ 1..97 FT /note="Missing (in isoform Alpha-C3)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058315" FT VAR_SEQ 1..89 FT /note="Missing (in isoform Alpha-C2)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058316" FT VAR_SEQ 1..85 FT /note="Missing (in isoform Alpha-C1)" FT /evidence="ECO:0000269|PubMed:15866175" FT /id="VSP_058317" FT VAR_SEQ 1..26 FT /note="Missing (in isoform Alpha-B and isoform Beta-B)" FT /evidence="ECO:0000305" FT /id="VSP_018773" FT VAR_SEQ 313..338 FT /note="Missing (in isoform 10)" FT /evidence="ECO:0000303|PubMed:17404046" FT /id="VSP_043908" FT VAR_SEQ 451 FT /note="G -> GR (in isoform Alpha-2 and isoform Beta-2)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007363" FT VAR_SEQ 491..674 FT /note="Missing (in isoform GR-A alpha and isoform GR-A FT beta)" FT /evidence="ECO:0000305" FT /id="VSP_013340" FT VAR_SEQ 728..777 FT /note="VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK FT -> NVMWLKPESTSHTLI (in isoform Beta, isoform Beta-B, FT isoform Beta-2 and isoform GR-A beta)" FT /evidence="ECO:0000303|PubMed:2867473" FT /id="VSP_003703" FT VARIANT 23 FT /note="R -> K (reduces transactivation activity; does not FT affect transrepression activity; dbSNP:rs6190)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10898924, ECO:0000269|PubMed:12351458, FT ECO:0000269|PubMed:15276593, ECO:0000269|PubMed:15292341, FT ECO:0000269|PubMed:16030164, ECO:0000269|PubMed:9150737, FT ECO:0000269|Ref.9" FT /id="VAR_014140" FT VARIANT 29 FT /note="F -> L (in dbSNP:rs148102613)" FT /evidence="ECO:0000269|PubMed:10898924" FT /id="VAR_015628" FT VARIANT 65 FT /note="F -> V (in dbSNP:rs6192)" FT /evidence="ECO:0000269|PubMed:10391209, ECO:0000269|Ref.9" FT /id="VAR_014622" FT VARIANT 72 FT /note="N -> D (associated in cis with A-321 and S-766 in FT one individual; doubles transactivation potential)" FT /evidence="ECO:0000269|PubMed:21701417" FT /id="VAR_075797" FT VARIANT 112 FT /note="L -> F (in dbSNP:rs542110718)" FT /evidence="ECO:0000269|PubMed:10898924" FT /id="VAR_015629" FT VARIANT 233 FT /note="D -> N (in dbSNP:rs1241576112)" FT /evidence="ECO:0000269|PubMed:10898924" FT /id="VAR_015630" FT VARIANT 321 FT /note="V -> A (associated in cis with D-72 and S-766 in one FT individual; doubles transactivation potential)" FT /evidence="ECO:0000269|PubMed:21701417" FT /id="VAR_075798" FT VARIANT 363 FT /note="N -> S (enhances transactivation activity; does not FT affect transrepression activity; may increase sensitivity FT to exogenously administered glucocorticoids; may contribute FT to central obesity in men and show lack of association with FT other risk factors for coronary heart disease and diabetes FT mellitus; dbSNP:rs56149945)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10898924, ECO:0000269|PubMed:11344238, FT ECO:0000269|PubMed:16030164, ECO:0000269|PubMed:8445027, FT ECO:0000269|PubMed:9150737" FT /id="VAR_004675" FT VARIANT 421 FT /note="C -> Y" FT /evidence="ECO:0000269|PubMed:8358735" FT /id="VAR_015631" FT VARIANT 423 FT /note="V -> A (in GCCR; uncertain significance; reduces FT transactivation activity; delays nuclear translocation; FT does not exert a dominant negative effect; impairs DNA FT binding)" FT /evidence="ECO:0000269|PubMed:23426617" FT /id="VAR_075799" FT VARIANT 477 FT /note="R -> H (in GCCR; dbSNP:rs104893913)" FT /evidence="ECO:0000269|PubMed:11589680" FT /id="VAR_013472" FT VARIANT 477 FT /note="R -> S (in GCCR; loss of DNA-binding and of FT transactivation activity; incomplete dexamethasone-induced FT translocation to the nucleus; no effect on FT dexamethasone-binding affinity compared with wild-type)" FT /evidence="ECO:0000269|PubMed:27120390" FT /id="VAR_077143" FT VARIANT 478 FT /note="Y -> C (in GCCR; decreased DNA-binding and FT transactivation activity; incomplete dexamethasone-induced FT translocation to the nucleus; no effect on FT dexamethasone-binding affinity compared with wild-type)" FT /evidence="ECO:0000269|PubMed:27120390" FT /id="VAR_077144" FT VARIANT 556 FT /note="T -> I (in GCCR; reduces transactivation activity; FT enhances transrepression activity; reduces affinity for FT ligand; delays nuclear translocation; does not exert a FT dominant negative effect; does not impair DNA binding)" FT /evidence="ECO:0000269|PubMed:21362280, FT ECO:0000269|PubMed:26541474" FT /id="VAR_075800" FT VARIANT 559 FT /note="I -> N (in GCCR; interferes with translocation to FT the nucleus and thereby strongly reduces transcription FT activation; is equally impaired in nuclear export; acts as FT dominant negative mutant; dbSNP:rs104893909)" FT /evidence="ECO:0000269|PubMed:11701741" FT /id="VAR_015632" FT VARIANT 571 FT /note="V -> A (in pseudohermaphroditism; female with FT hypokalemia due to glucocorticoid resistance; 6-fold FT reduction in binding affinity compared with the wild-type FT receptor; dbSNP:rs104893911)" FT /evidence="ECO:0000269|PubMed:11932321" FT /id="VAR_025014" FT VARIANT 575 FT /note="V -> G (in GCCR; uncertain significance; reduces FT transactivation activity; enhances transrepression FT activity; reduces affinity for ligand; delays nuclear FT translocation; does not exert a dominant negative effect; FT does not impair DNA binding)" FT /evidence="ECO:0000269|PubMed:24483153" FT /id="VAR_075801" FT VARIANT 641 FT /note="D -> V (in GCCR; dbSNP:rs104893908)" FT /evidence="ECO:0000269|PubMed:1704018" FT /id="VAR_004676" FT VARIANT 672 FT /note="L -> P (in GCCR; loss of dexamethasone-binding, FT dexamethasone-induced translocation to the nucleus and of FT transactivation activity)" FT /evidence="ECO:0000269|PubMed:27120390" FT /id="VAR_077145" FT VARIANT 679 FT /note="G -> S (in GCCR; has 50% binding affinity; FT dbSNP:rs104893914)" FT /evidence="ECO:0000269|PubMed:11589680" FT /id="VAR_013473" FT VARIANT 714 FT /note="R -> Q (in GCCR; uncertain significance; reduces FT transactivation; reduces affinity for ligand; exerts a FT dominant negative effect; does not impair DNA binding)" FT /evidence="ECO:0000269|PubMed:20335448" FT /id="VAR_075802" FT VARIANT 726 FT /note="H -> R (in GCCR; uncertain significance; reduces FT transactivation and transrepression activity; reduces FT affinity for ligand; delays nuclear translocation; does not FT impair DNA binding)" FT /evidence="ECO:0000269|PubMed:26031419" FT /id="VAR_075803" FT VARIANT 729 FT /note="V -> I (in GCCR; dbSNP:rs1027058734)" FT /evidence="ECO:0000269|PubMed:7683692" FT /id="VAR_004677" FT VARIANT 737 FT /note="F -> L (in GCCR; reduces transactivation of the FT glucocorticoid-inducible tumor virus promoter; reduces FT affinity for ligand; delays its nuclear translocation; acts FT as dominant negative mutant; dbSNP:rs121909727)" FT /evidence="ECO:0000269|PubMed:17635946" FT /id="VAR_071935" FT VARIANT 747 FT /note="I -> M (in GCCR; alters interaction with NCOA2 and FT strongly reduces transcription activation; acts as a FT dominant negative mutant; dbSNP:rs104893910)" FT /evidence="ECO:0000269|PubMed:12050230" FT /id="VAR_015633" FT VARIANT 753 FT /note="L -> F (in dbSNP:rs121909726)" FT /evidence="ECO:0000269|PubMed:8316249, FT ECO:0000269|PubMed:8358735" FT /id="VAR_004678" FT VARIANT 766 FT /note="N -> S (associated in cis with D-72 and A-321 in one FT individual; doubles transactivation potential)" FT /evidence="ECO:0000269|PubMed:21701417" FT /id="VAR_075804" FT VARIANT 773 FT /note="L -> P (in GCCR; reduces transactivation of the FT glucocorticoid-inducible tumor virus promoter; reduces FT affinity for ligand; delays its nuclear translocation; acts FT as dominant negative mutant; dbSNP:rs104893912)" FT /evidence="ECO:0000269|PubMed:15769988" FT /id="VAR_071936" FT MUTAGEN 1 FT /note="M->T: Abolishes expression of A-type isoforms." FT /evidence="ECO:0000269|PubMed:11435610, FT ECO:0000269|PubMed:15866175" FT MUTAGEN 27 FT /note="M->T: Abolishes expression of B-type isoforms." FT /evidence="ECO:0000269|PubMed:11435610, FT ECO:0000269|PubMed:15866175" FT MUTAGEN 86 FT /note="M->I: Abolishes expression of C-type isoforms; when FT associated with I-90 and I-98." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 90 FT /note="M->I: Abolishes expression of C-type isoforms; when FT associated with I-86 and I-98." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 98 FT /note="M->I: Abolishes expression of C-type isoforms; when FT associated with I-86 and I-90." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 101 FT /note="D->A: Reduces transcription activation activity of FT isoform Alpha-C3 by half." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 101 FT /note="D->K: Reduces transcription activation activity of FT isoform Alpha-C3 by half. Suppresses apoptosis-inducing FT activity of isoform Alpha-C3. Impairs recruitment of FT selected coregulators onto DNA binding sites." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 106..107 FT /note="QQ->LL: Reduces activity of isoform Alpha-C3 by FT half." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 113..114 FT /note="SS->AA: Does not affect the activity of isoform FT Alpha-C3." FT /evidence="ECO:0000269|PubMed:23820903" FT MUTAGEN 191 FT /note="F->D: Reduces transactivation by the ADA complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 193 FT /note="I->D: Reduces transactivation by the ADA complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 194 FT /note="L->A: Strongly reduces transactivation by the ADA FT complex; when associated with V-224 and F-225." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 197 FT /note="L->E: Reduces transactivation by the ADA complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 211 FT /note="S->A: Reduces expression of target genes IGFBP1 and FT IRF8." FT /evidence="ECO:0000269|PubMed:18483179" FT MUTAGEN 213 FT /note="W->A: Strongly reduces transactivation by the ADA FT complex." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 224 FT /note="L->V: Strongly reduces transactivation by the ADA FT complex; when associated with A-194 and F-225." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 225 FT /note="L->F: Strongly reduces transactivation by the ADA FT complex; when associated with A-194 and V-224." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 226 FT /note="S->A: Abolishes phosphorylation and enhances FT transcriptional activation." FT /evidence="ECO:0000269|PubMed:18483179" FT MUTAGEN 235 FT /note="F->L: Strongly reduces transactivation by the ADA FT complex; when associated with V-236." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 236 FT /note="L->V: Strongly reduces transactivation by the ADA FT complex; when associated with L-235." FT /evidence="ECO:0000269|PubMed:9154805" FT MUTAGEN 277 FT /note="K->R: Strongly reduces sumoylation. Almost complete FT loss of sumoylation; when associated with R-293." FT /evidence="ECO:0000269|PubMed:12144530" FT MUTAGEN 293 FT /note="K->R: Strongly reduces sumoylation. Almost complete FT loss of sumoylation; when associated with R-277." FT /evidence="ECO:0000269|PubMed:12144530" FT MUTAGEN 316 FT /note="M->I: Abolishes expression of D-type isoforms; when FT associated with I-331 and I-336." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 331 FT /note="M->I: Abolishes expression of D-type isoforms; when FT associated with I-316 and I-336." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 336 FT /note="M->I: Abolishes expression of D-type isoforms; when FT associated with I-316 and I-331." FT /evidence="ECO:0000269|PubMed:15866175" FT MUTAGEN 404 FT /note="S->A: Abolishes phosphorylation. Does not affect FT translocation to the nucleus following ligand stimulation. FT Increases protein half-life and transcriptional repressor FT activity. Alters repertoire of regulated genes. Increases FT cell death." FT /evidence="ECO:0000269|PubMed:18838540" FT MUTAGEN 404 FT /note="S->D: Does not affect translocation to the nucleus FT following ligand stimulation." FT /evidence="ECO:0000269|PubMed:18838540" FT MUTAGEN 480 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer. FT Complete loss in acetylation and in repression of its FT transcriptional activity by CLOCK-BMAL1 heterodimer; when FT associated with A-492; A-494 and A-495." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 492 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer. FT Complete loss in acetylation and in repression of its FT transcriptional activity by CLOCK-BMAL1 heterodimer; when FT associated with A-480; A-494 and A-495." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 494 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer; FT when associated with A-495. Complete loss in acetylation FT and in repression of its transcriptional activity by FT CLOCK-BMAL1 heterodimer; when associated with A-480; A-492 FT and A-495." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 495 FT /note="K->A: Decrease in acetylation and in repression of FT its transcriptional activity by CLOCK-BMAL1 heterodimer; FT when associated with A-494. Complete loss in acetylation FT and in repression of its transcriptional activity by FT CLOCK-BMAL1 heterodimer; when associated with A-480; A-492 FT and A-494." FT /evidence="ECO:0000269|PubMed:19141540" FT MUTAGEN 585 FT /note="R->A: Reduces activation mediated by ligand binding FT domain; when associated with A-590." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 590 FT /note="D->A: Reduces activation mediated by ligand binding FT domain; when associated with A-585." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 602 FT /note="F->S: Increases solubility. No effect on FT transactivation by dexamethasone." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 625 FT /note="P->A: Decreases transactivation by dexamethasone by FT 95%." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 628 FT /note="I->A: Decreases dimerization and transactivation by FT dexamethasone; when associated with S-602." FT /evidence="ECO:0000269|PubMed:12151000" FT MUTAGEN 703 FT /note="K->R: Slightly reduces sumoylation. Inhibits the FT stimulatory effect of RWDD3 on its transcriptional FT activity." FT /evidence="ECO:0000269|PubMed:12144530, FT ECO:0000269|PubMed:23508108" FT CONFLICT 399 FT /note="R -> G (in Ref. 7; BAD97314)" FT /evidence="ECO:0000305" FT CONFLICT 754 FT /note="A -> T (in Ref. 7; BAD97314)" FT /evidence="ECO:0000305" FT TURN 422..424 FT /evidence="ECO:0007829|PDB:5E69" FT STRAND 430..432 FT /evidence="ECO:0007829|PDB:5E69" FT STRAND 435..437 FT /evidence="ECO:0007829|PDB:5E69" FT HELIX 439..450 FT /evidence="ECO:0007829|PDB:5E69" FT STRAND 458..461 FT /evidence="ECO:0007829|PDB:5E69" FT TURN 467..472 FT /evidence="ECO:0007829|PDB:5E69" FT HELIX 474..484 FT /evidence="ECO:0007829|PDB:5E69" FT HELIX 488..497 FT /evidence="ECO:0007829|PDB:6CFN" FT TURN 525..527 FT /evidence="ECO:0007829|PDB:1M2Z" FT HELIX 532..538 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 550..552 FT /evidence="ECO:0007829|PDB:3K22" FT HELIX 556..579 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 584..586 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 589..615 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 617..619 FT /evidence="ECO:0007829|PDB:4P6W" FT STRAND 621..624 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 627..629 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 631..634 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 639..655 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 660..671 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 673..675 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 683..702 FT /evidence="ECO:0007829|PDB:4UDD" FT STRAND 704..706 FT /evidence="ECO:0007829|PDB:4P6W" FT HELIX 708..741 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 743..745 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 751..765 FT /evidence="ECO:0007829|PDB:4UDD" FT HELIX 766..768 FT /evidence="ECO:0007829|PDB:6DXK" FT STRAND 769..771 FT /evidence="ECO:0007829|PDB:5UC3" FT MOD_RES P04150-8:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES P04150-9:1 FT /note="N-acetylmethionine" FT /evidence="ECO:0007744|PubMed:22814378" SQ SEQUENCE 777 AA; 85659 MW; C5C90C9A5DD16AAB CRC64; MDSKESLTPG REENPSSVLA QERGDVMDFY KTLRGGATVK VSASSPSLAV ASQSDSKQRR LLVDFPKGSV SNAQQPDLSK AVSLSMGLYM GETETKVMGN DLGFPQQGQI SLSSGETDLK LLEESIANLN RSTSVPENPK SSASTAVSAA PTEKEFPKTH SDVSSEQQHL KGQTGTNGGN VKLYTTDQST FDILQDLEFS SGSPGKETNE SPWRSDLLID ENCLLSPLAG EDDSFLLEGN SNEDCKPLIL PDTKPKIKDN GDLVLSSPSN VTLPQVKTEK EDFIELCTPG VIKQEKLGTV YCQASFPGAN IIGNKMSAIS VHGVSTSGGQ MYHYDMNTAS LSQQQDQKPI FNVIPPIPVG SENWNRCQGS GDDNLTSLGT LNFPGRTVFS NGYSSPSMRP DVSSPPSSSS TATTGPPPKL CLVCSDEASG CHYGVLTCGS CKVFFKRAVE GQHNYLCAGR NDCIIDKIRR KNCPACRYRK CLQAGMNLEA RKTKKKIKGI QQATTGVSQE TSENPGNKTI VPATLPQLTP TLVSLLEVIE PEVLYAGYDS SVPDSTWRIM TTLNMLGGRQ VIAAVKWAKA IPGFRNLHLD DQMTLLQYSW MFLMAFALGW RSYRQSSANL LCFAPDLIIN EQRMTLPCMY DQCKHMLYVS SELHRLQVSY EEYLCMKTLL LLSSVPKDGL KSQELFDEIR MTYIKELGKA IVKREGNSSQ NWQRFYQLTK LLDSMHEVVE NLLNYCFQTF LDKTMSIEFP EMLAEIITNQ IPKYSNGNIK KLLFHQK //