GCR_HUMAN
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 03-AUG-2022, entry version 276.
DE RecName: Full=Glucocorticoid receptor;
DE Short=GR;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 1;
GN Name=NR3C1; Synonyms=GRL;
OS 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 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 [74]
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 [75]
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 [76]
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 [77]
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 [78]
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 [79]
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 [80]
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 [81]
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 [82]
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 [83]
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 [84]
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 [85]
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 [86]
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 [87]
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 [88]
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 [89]
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 [90]
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 [91]
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 [92]
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 [93]
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 [94]
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 [95]
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 [96]
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 [97]
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 [98]
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 [99]
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 [100]
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 [101]
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 Affects inflammatory responses, cellular proliferation and
CC differentiation in target tissues. Involved in chromatin remodeling
CC (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to
CC the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-
CC dependent manner which recruits the RNA helicase UPF1 and the mRNA-
CC decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could
CC act as a coactivator for STAT5-dependent transcription upon growth
CC hormone (GH) stimulation and could reveal an essential role of hepatic
CC GR in the control of body growth (By similarity).
CC {ECO:0000250|UniProtKB:P06537, ECO:0000269|PubMed:25775514,
CC ECO:0000269|PubMed:27120390, 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). {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:29127155, ECO:0000269|PubMed:9154805,
CC ECO:0000269|PubMed:9353307, 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";
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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. [P04150-3]
DR RefSeq; XP_005268480.1; XM_005268423.3. [P04150-3]
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; 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 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; 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 AlphaFoldDB; P04150; -.
DR SMR; P04150; -.
DR BioGRID; 109165; 1488.
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 GlyGen; P04150; 6 sites, 2 O-linked glycans (6 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; P04150; -.
DR PeptideAtlas; P04150; -.
DR PRIDE; 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 Antibodypedia; 1329; 1342 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 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; 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; NLPCMYD; -.
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 SignaLink; P04150; -.
DR SIGNOR; P04150; -.
DR BioGRID-ORCS; 2908; 13 hits in 1109 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 210 other tissues.
DR ExpressionAtlas; P04150; baseline and differential.
DR Genevisible; P04150; HS.
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:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
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: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: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: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:0007049; P:cell cycle; IEA:UniProtKB-KW.
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: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:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
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: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:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR DisProt; DP00030; -.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 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 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; SSF48508; SSF48508; 1.
DR PROSITE; PS51843; NR_LBD; 1.
DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1.
DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; 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 (variant of uncertain significance;
FT associated in cis with A-321 and S-766 in one individual;
FT 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 (variant of uncertain significance;
FT associated in cis with D-72 and S-766 in one individual;
FT 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; unknown pathological significance;
FT reduces transactivation activity; delays nuclear
FT translocation; does not exert a dominant negative effect;
FT impairs DNA 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 dexamethasone-
FT 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 dexamethasone-
FT 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; unknown pathological significance;
FT reduces 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; unknown pathological significance;
FT reduces transactivation; reduces affinity for ligand;
FT exerts a dominant negative effect; does not impair DNA
FT binding)"
FT /evidence="ECO:0000269|PubMed:20335448"
FT /id="VAR_075802"
FT VARIANT 726
FT /note="H -> R (in GCCR; unknown pathological significance;
FT reduces transactivation and transrepression activity;
FT reduces affinity for ligand; delays nuclear translocation;
FT does not 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 dominant
FT 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 (variant of uncertain significance;
FT associated in cis with D-72 and A-321 in one individual;
FT 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-ARNTL/BMAL1
FT heterodimer. Complete loss in acetylation and in repression
FT of its transcriptional activity by CLOCK-ARNTL/BMAL1
FT heterodimer; when 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-ARNTL/BMAL1
FT heterodimer. Complete loss in acetylation and in repression
FT of its transcriptional activity by CLOCK-ARNTL/BMAL1
FT heterodimer; when 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-ARNTL/BMAL1
FT heterodimer; when associated with A-495. Complete loss in
FT acetylation and in repression of its transcriptional
FT activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated
FT with A-480; A-492 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-ARNTL/BMAL1
FT heterodimer; when associated with A-494. Complete loss in
FT acetylation and in repression of its transcriptional
FT activity by CLOCK-ARNTL/BMAL1 heterodimer; when associated
FT with A-480; A-492 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
