ID GCR_HUMAN Reviewed; 777 AA. AC P04150; P04151; Q53EP5; Q6N0A4; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 07-JUL-2009, entry version 150. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). RC TISSUE=Fibroblast; RX MEDLINE=86092206; 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 MEDLINE=91201378; PubMed=1707881; 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 [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 RT isoform of the human glucocorticoid receptor."; RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] 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., Blocker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., RA Ottenwalder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] 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 [7] 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., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA 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 [8] 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-394. RX MEDLINE=91224961; PubMed=2026589; 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 RT factor."; RL J. Biol. Chem. 266:8711-8719(1991). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-394. RX MEDLINE=92068829; 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 RT regulation."; RL J. Steroid Biochem. Mol. Biol. 40:317-323(1991). RN [11] RP DOMAINS. RX MEDLINE=86092211; 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 RT relationship to the v-erb-A oncogene product."; RL Nature 318:670-672(1985). RN [12] RP ALTERNATIVE SPLICING (ISOFORMS GP-P; GP-A ALPHA AND GP-A BETA). RX MEDLINE=93364877; 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 [13] RP INTERACTION WITH TADA2L AND THE ADA COMPLEX, AND MUTAGENESIS OF RP PHE-191; ILE-193; LEU-194; LEU-197; TRP-213; LEU-224; LEU-225; PHE-235 RP AND LEU-236. RX MEDLINE=97299656; PubMed=9154805; 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 RT glucocorticoid receptor."; RL Mol. Cell. Biol. 17:3065-3073(1997). RN [14] RP INTERACTION WITH THE SMARCA4 COMPLEX; NCOA1; NCOA2 AND THE RP CREBBP/EP300 COMPLEX. RX MEDLINE=98250578; PubMed=9590696; DOI=10.1038/30032; RA Fryer C.J., Archer T.K.; RT "Chromatin remodelling by the glucocorticoid receptor requires the RT BRG1 complex."; RL Nature 393:88-91(1998). RN [15] RP INTERACTION WITH BAG1. RX MEDLINE=99408777; 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 RT downregulation of glucocorticoid receptor activity."; RL J. Cell Biol. 146:929-940(1999). RN [16] RP ALTERNATIVE SPLICING (ISOFORMS ALPHA-2 AND BETA-2). RX MEDLINE=20030962; PubMed=10566686; DOI=10.1210/jc.84.11.4283; RA Rivers C., Levy A., Hancock J., Lightman S., Norman M.; RT "Insertion of an amino acid in the DNA-binding domain of the RT glucocorticoid receptor as a result of alternative splicing."; RL J. Clin. Endocrinol. Metab. 84:4283-4286(1999). RN [17] RP TISSUE SPECIFICITY. RX MEDLINE=20358609; PubMed=10902803; DOI=10.1210/jc.85.7.2519; 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 [18] RP INTERACTION WITH NCOA6. RX MEDLINE=20325329; PubMed=10866662; RX 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 [19] RP EFFECT ON EXPANDED POLYGLUTAMINE PROTEIN. RX MEDLINE=20105528; 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 [20] RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION. RX MEDLINE=21560972; 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 [21] RP REDUCTION OF CELL DEATH IN RESPONSE TO CORTICOSTEROIDS. RX MEDLINE=21136238; PubMed=11238589; DOI=10.1084/jem.193.5.585; RA Strickland I., Kisich K., Hauk P.J., Vottero A., Chrousos G.P., RA Klemm D.J., 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 RT response to corticosteroids."; RL J. Exp. Med. 193:585-593(2001). RN [22] RP ALTERNATIVE INITIATION, AND MUTAGENESIS OF MET-1 AND MET-27. RX MEDLINE=21329577; PubMed=11435610; DOI=10.1210/me.15.7.1093; 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 [23] RP SUMOYLATION, AND MUTAGENESIS OF LYS-277; LYS-293 AND LYS-703. RX MEDLINE=22280317; 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 [24] RP PHOSPHORYLATION AT SER-203 AND SER-211. RX MEDLINE=22113030; PubMed=12000743; DOI=10.1074/jbc.M110530200; RA Wang Z., Frederick J., Garabedian M.J.; RT "Deciphering the phosphorylation 'code' of the glucocorticoid receptor RT in vivo."; RL J. Biol. Chem. 277:26573-26580(2002). RN [25] RP INTERACTION WITH PELP1. RX MEDLINE=22317447; 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 [26] RP REVIEW ON ALTERNATIVE SPLICING, ALTERNATIVE INITIATION, AND RP POST-TRANSLATIONAL MODIFICATIONS. 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 [27] 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 [28] RP INTERACTION WITH HEXIM1. RX PubMed=15941832; DOI=10.1073/pnas.0409863102; RA Shimizu N., Ouchida R., Yoshikawa N., Hisada T., Watanabe H., RA Okamoto K., 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 RT elongation factor b."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8555-8560(2005). RN [29] 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., RA Wood W.M., 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 [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-8 AND SER-45, AND MASS RP SPECTROMETRY. 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134; SER-226; SER-234 RP AND SER-267, AND MASS SPECTROMETRY. 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 [32] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [33] 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 RP ARG-585; ASP-590; PHE-602; PRO-625 AND ILE-628. RX MEDLINE=22145916; 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 RT domain reveals a novel mode of receptor dimerization and coactivator RT recognition."; RL Cell 110:93-105(2002). RN [34] 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 MEDLINE=22692510; 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., RA Thorell S., Oehman L., Greer J., Gustafsson J.-A., Carlstedt-Duke J., RA Carlquist M.; RT "The three-dimensional structures of antagonistic and agonistic forms RT of 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 [35] RP CHARACTERIZATION OF VARIANT GLUCOCORTICOID RESISTANCE VAL-641. RX MEDLINE=91123468; PubMed=1704018; 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 RT hormone binding domain of the glucocorticoid receptor in familial RT glucocorticoid resistance."; RL J. Clin. Invest. 87:680-686(1991). RN [36] RP VARIANTS TYR-421 AND PHE-753. RX MEDLINE=93364907; 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 [37] RP VARIANT SER-363. RX MEDLINE=93187003; PubMed=8445027; DOI=10.1210/jc.76.3.683; RA Karl M., Lamberts S.W.J., Detera-Wadleigh S.D., Encio I.J., RA Stratakis C.A., Hurley D.M., Accili D., Chrousos G.P.; RT "Familial glucocorticoid resistance caused by a splice site deletion RT in the human glucocorticoid receptor gene."; RL J. Clin. Endocrinol. Metab. 76:683-689(1993). RN [38] RP VARIANT GLUCOCORTICOID RESISTANCE ILE-729. RX MEDLINE=93253031; PubMed=7683692; 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 [39] RP VARIANT PHE-753. RX MEDLINE=93302771; PubMed=8316249; DOI=10.1210/me.7.5.631; RA Ashraf J., Thompson E.B.; RT "Identification of the activation-labile gene: a single point mutation RT in the human glucocorticoid receptor presents as two distinct receptor RT phenotypes."; RL Mol. Endocrinol. 7:631-642(1993). RN [40] RP VARIANTS LYS-23 AND SER-363. RX MEDLINE=97295085; 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 RT glucocorticoid receptor gene and glucocorticoid resistance."; RL Hum. Genet. 99:663-668(1997). RN [41] RP VARIANTS LYS-23; VAL-65 AND SER-363. RX MEDLINE=99318093; 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 RT of human genes."; RL Nat. Genet. 22:231-238(1999). RN [42] RP ERRATUM. 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 [43] RP VARIANTS LYS-23; LEU-29; PHE-112; ASN-233 AND SER-363. RX MEDLINE=20357652; 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 RT glucocorticoid receptor: no association with puerperal psychosis or RT schizophrenia."; RL Am. J. Med. Genet. 96:412-417(2000). RN [44] RP VARIANTS GLUCOCORTICOID RESISTANCE HIS-477 AND SER-679. RX MEDLINE=21473978; PubMed=11589680; RX DOI=10.1046/j.1365-2265.2001.01323.x; RA Ruiz M., Lind U., Gaafvels M., Eggertsen G., Carlstedt-Duke J., RA Nilsson L., Holtmann M., Stierna P., Wikstroem A.-C., Werner S.; RT "Characterization of two novel mutations in the glucocorticoid RT receptor gene in patients with primary cortisol resistance."; RL Clin. Endocrinol. (Oxf.) 55:363-371(2001). RN [45] RP VARIANT SER-363. RX MEDLINE=21242823; PubMed=11344238; DOI=10.1210/jc.86.5.2270; 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 RT other risk factors for coronary heart disease and diabetes mellitus."; RL J. Clin. Endocrinol. Metab. 86:2270-2274(2001). RN [46] RP CHARACTERIZATION OF VARIANT GLUCOCORTICOID RESISTANCE ASN-559. RX MEDLINE=21558592; PubMed=11701741; DOI=10.1210/jc.86.11.5600; 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: RT importance of the ligand-binding domain for intracellular GR RT trafficking."; RL J. Clin. Endocrinol. Metab. 86:5600-5608(2001). RN [47] RP VARIANT LYS-23. RX PubMed=12351458; 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 RT and cholesterol levels."; RL Diabetes 51:3128-3134(2002). RN [48] RP VARIANT PSEUDOHERMAPHRODITISM ALA-571. RX MEDLINE=21929897; PubMed=11932321; DOI=10.1210/jc.87.4.1805; 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 [49] RP VARIANT GLUCOCORTICOID RESISTANCE MET-747, AND ALTERED INTERACTION RP WITH THE COACTIVATOR NCOA2. RX MEDLINE=22045363; PubMed=12050230; DOI=10.1210/jc.87.6.2658; RA Vottero A., Kino T., Combe H., Lecomte P., Chrousos G.P.; RT "A novel, C-terminal dominant negative mutation of the GR causes RT familial glucocorticoid resistance through abnormal interactions with RT p160 steroid receptor coactivators."; RL J. Clin. Endocrinol. Metab. 87:2658-2667(2002). RN [50] 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., RA Uitterlinden A.G., Janssen J.A.M.J.L., Ester W., Brinkmann A.O., RA Grobbee D.E., de Jong F.H., Pols H.A.P., Koper J.W., Lamberts S.W.J.; RT "Association of the ER22/23EK polymorphism in the glucocorticoid RT receptor gene with survival and C-reactive protein levels in elderly RT men."; RL Am. J. Med. 117:158-162(2004). RN [51] 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 RT young adults."; RL J. Clin. Endocrinol. Metab. 89:4004-4009(2004). CC -!- FUNCTION: Receptor for glucocorticoids (GC). Has a dual mode of CC action: as a transcription factor that binds to glucocorticoid CC response elements (GRE) and as a modulator of other transcription CC factors. Affects inflammatory responses, cellular proliferation CC and differentiation in target tissues. Could act as a coactivator CC for STAT5-dependent transcription upon growth hormone (GH) CC stimulation and could reveal an essential role of hepatic GR in CC the control of body growth. Involved in chromatin remodeling. CC Plays a significant role in transactivation. Involved in nuclear CC translocation (By similarity). CC -!- SUBUNIT: Heteromultimeric cytoplasmic complex with HSP90, HSP70, CC and FKBP5 or another immunophilin, or the immunophilin homolog CC PPP5C. Directly interacts with UNC45A. Upon ligand binding FKBP5 CC dissociates from the complex and FKBP4 takes its place, thereby CC linking the complex to dynein and mediating transport to the CC nucleus, where the complex dissociates (By similarity). Binds to CC DNA as a homodimer, and as a heterodimer with NR3C2 or the CC retinoid X receptor. Binds STAT5A and STAT5B homodimers and CC heterodimers. Interacts with NRIP1, POU2F1, POU2F2 and TRIM28. CC Interacts with NCOA1, NCOA3, SMARCA4, SMARCC1, SMARCD1, and CC SMARCE1 (By similarity). Interacts with several coactivator CC complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L and CC p160 coactivators such as NCOA2 and NCOA6. Interaction with BAG1 CC inhibits transactivation. Interacts with HEXIM1, PELP1 and CC TGFB1I1. CC -!- INTERACTION: CC Q62667:Mvp (xeno); NbExp=1; IntAct=EBI-493507, EBI-918333; CC P51532:SMARCA4; NbExp=1; IntAct=EBI-493507, EBI-302489; CC Q92922:SMARCC1; NbExp=1; IntAct=EBI-493507, EBI-355653; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic in the CC absence of ligand, nuclear after ligand-binding. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=9; CC Comment=At least 4 isoforms, Alpha (shown here), Alpha-B, Beta CC and Beta-B, are produced by alternative initiation at Met-1 and CC Met-27. The existence of isoform Alpha and isoform Alpha-B has CC been proved by mutagenesis. As the sequence environment of the 2 CC potential ATG initiator codons is the same for the other CC altrnatively spliced isoforms, alternative initiation of CC translation could also occur on these transcripts. Additional CC isoforms seem to exist; CC Name=Alpha; Synonyms=Alpha-A; CC IsoId=P04150-1; Sequence=Displayed; CC Note=Predominant physiological form. Isoform Alpha-B is produced CC by alternative initiation at Met-27 of isoform Alpha. Both CC isoforms exhibit similar subcellular location and nuclear CC translocation after ligand activation. Isoform Alpha-B appears CC to be more susceptible to degradation, at least when expressed CC in mammalian cells, but more effective in transcriptional CC activation and not in transrepression; CC Name=Beta; Synonyms=Beta-A; CC IsoId=P04150-2; Sequence=VSP_003703; CC Note=No hormone-binding activity. Widely expressed at low level. CC Localized largely in the nucleus; CC Name=Alpha-2; Synonyms=Gamma; CC IsoId=P04150-3; Sequence=VSP_007363; CC Note=Due to a partial intron retention. Lower transcriptional CC activity. Expressed at low level; CC Name=Beta-2; CC IsoId=P04150-6; Sequence=VSP_007363, VSP_003703; CC Note=Due to a partial intron retention; CC Name=GR-A alpha; CC IsoId=P04150-5; Sequence=VSP_013340; CC Note=Lacks exons 5, 6 and 7. Found in glucocorticoid-resistant CC myeloma patients; CC Name=GR-A beta; CC IsoId=P04150-7; Sequence=VSP_013340, VSP_003703; CC Note=Lacks exons 5, 6 and 7; CC Name=GR-P; CC IsoId=P04150-4; Sequence=Not described; CC Note=Encoded by exons 2-7 plus several basepairs from the CC subsequent intron region. Lacks the ligand binding domain. CC Accounts for up to 10-20% of mRNAs; CC Name=Alpha-B; Synonyms=Beta-B; CC IsoId=P04150-8; Sequence=VSP_018773; CC Note=Produced by alternative initiation at Met-27 of isoform CC Alpha. Both isoforms exhibit similar subcellular location and CC nuclear translocation after ligand activation. Isoform Alpha-B CC appears to be more susceptible to degradation, at least when CC expressed in mammalian cells, but more effective in CC transcriptional activation and not in transrepression; CC Name=Beta-B; CC IsoId=P04150-9; Sequence=VSP_018773, VSP_003703; CC Note=Produced by alternative initiation at Met-27 of isoform CC Beta; CC -!- TISSUE SPECIFICITY: Widely expressed. In the heart, detected in CC left and right atria, left and right ventricles, aorta, apex, CC intraventricular septum, and atrioventricular node as well as CC whole adult and fetal heart. CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, CC a DNA-binding domain and a C-terminal steroid-binding domain. CC -!- PTM: Increased proteasome-mediated degradation in response to CC glucocorticoids. CC -!- PTM: Phosphorylated in the absence of hormone; becomes CC hyperphosphorylated in the presence of glucocorticoid. The Ser- CC 203-phosphorylated form is mainly cytoplasmic, and the Ser-211- CC phosphorylated form is nuclear. Transcriptional activity CC correlates with the amount of phosphorylation at Ser-211. CC -!- PTM: Sumoylated; this reduces transcription transactivation. CC -!- PTM: Ubiquitinated; restricts glucocorticoid-mediated CC transcriptional signaling (By similarity). CC -!- POLYMORPHISM: Carriers of the 22-Glu-Lys-23 allele are relatively CC more resistant to the effects of GCs with respect to the CC sensitivity of the adrenal feedback mechanism than non-carriers, CC resulting in a better metabolic health profile. Carriers have a CC better survival than non-carriers, as well as lower serum CRP CC levels. The 22-Glu-Lys-23 polymorphism is associated with a sex- CC specific, beneficial body composition at young-adult age, as well CC as greater muscle strength in males. CC -!- DISEASE: Defects in NR3C1 are a cause of glucocorticoid resistance CC [MIM:138040]; also known as cortisol resistance. It is a CC hypertensive, hyperandrogenic disorder characterized by increased CC serum cortisol concentrations. Inheritance is autosomal dominant. CC -!- MISCELLANEOUS: High constitutive expression of isoform beta by CC neutrophils may provide a mechanism by which these cells escape CC glucocorticoid-induced cell death. Up-regulation by CC proinflammatory cytokines such as IL8 further enhances their CC survival in the presence of glucocorticoids during inflammation. CC -!- MISCELLANEOUS: Can up- or down-modulate aggregation and nuclear CC localization of expanded polyglutamine polypeptides derived from CC AR and HD through specific regulation of gene expression. CC Aggregation and nuclear localization of expanded polyglutamine CC proteins are regulated cellular processes that can be modulated by CC this receptor, a well-characterized transcriptional regulator. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3 CC subfamily. CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=NR3C1"; 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="http://en.wikipedia.org/wiki/Glucocorticoid_receptor"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X03225; CAA26976.1; -; mRNA. DR EMBL; X03348; CAA27054.1; -; mRNA. DR EMBL; U80946; AAB64353.1; -; Genomic_DNA. DR EMBL; U78506; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U78507; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U78508; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U78509; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U78510; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U78511; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U78512; AAB64353.1; JOINED; Genomic_DNA. DR EMBL; U80947; AAB64354.1; -; Genomic_DNA. DR EMBL; U78506; AAB64354.1; JOINED; Genomic_DNA. DR EMBL; U78507; AAB64354.1; JOINED; Genomic_DNA. DR EMBL; U78508; AAB64354.1; JOINED; Genomic_DNA. DR EMBL; U78509; AAB64354.1; JOINED; Genomic_DNA. DR EMBL; U78510; AAB64354.1; JOINED; Genomic_DNA. DR EMBL; U78511; AAB64354.1; JOINED; Genomic_DNA. DR EMBL; U78512; AAB64354.1; JOINED; Genomic_DNA. 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; AC005601; AAC34207.1; -; Genomic_DNA. DR EMBL; AC004782; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091925; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015610; AAH15610.1; -; mRNA. DR EMBL; M69104; AAA88049.1; -; Genomic_DNA. DR EMBL; M73816; AAA53151.1; -; Genomic_DNA. DR EMBL; S68378; AAB20466.1; -; Genomic_DNA. DR IPI; IPI00022282; -. DR IPI; IPI00219946; -. DR IPI; IPI00251749; -. DR IPI; IPI00555880; -. DR IPI; IPI00604604; -. DR IPI; IPI00604725; -. DR IPI; IPI00759700; -. DR IPI; IPI00759729; -. DR PIR; A93370; QRHUGA. DR PIR; B93370; QRHUGB. DR RefSeq; NP_000167.1; -. DR RefSeq; NP_001018084.1; -. DR RefSeq; NP_001018085.1; -. DR RefSeq; NP_001018086.1; -. DR RefSeq; NP_001018087.1; -. DR RefSeq; NP_001018661.1; -. DR RefSeq; NP_001019265.1; -. DR UniGene; Hs.122926; -. 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 PDBsum; 1M2Z; -. DR PDBsum; 1NHZ; -. DR PDBsum; 1P93; -. DR PDBsum; 3BQD; -. DR PDBsum; 3CLD; -. DR PDBsum; 3E7C; -. DR SMR; P04150; 417-491. DR DisProt; DP00030; -. DR DIP; DIP:576N; -. DR IntAct; P04150; 3. DR PhosphoSite; P04150; -. DR PRIDE; P04150; -. DR Ensembl; ENSG00000113580; Homo sapiens. DR GeneID; 2908; -. DR KEGG; hsa:2908; -. DR UCSC; uc003lmy.1; human. DR UCSC; uc003lmz.1; human. DR UCSC; uc003lna.1; human. DR GeneCards; GC05M142639; -. DR H-InvDB; HIX0005273; -. DR HGNC; HGNC:7978; NR3C1. DR HPA; CAB010435; -. DR HPA; HPA004248; -. DR MIM; 138040; gene+phenotype. DR Orphanet; 786; Glucocorticoid resistance. DR PharmGKB; PA181; -. DR HOVERGEN; P04150; -. DR OMA; P04150; LPDTKPK. DR Pathway_Interaction_DB; hnf3bpathway; FOXA2 and FOXA3 transcription factor networks. DR Pathway_Interaction_DB; ar_tf_pathway; Regulation of Androgen receptor activity. DR Pathway_Interaction_DB; smad2_3nuclearpathway; Regulation of nuclear SMAD2/3 signaling. DR Pathway_Interaction_DB; hdac_classii_pathway; Signaling events mediated by HDAC Class II. DR Reactome; REACT_71; Gene Expression. DR BindingDB; P04150; -. DR DrugBank; DB00288; Amcinonide. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB01222; Budesonide. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB00663; Flumethasone Pivalate. DR DrugBank; DB00180; Flunisolide. DR DrugBank; DB00588; Fluticasone Propionate. DR DrugBank; DB00769; Hydrocortamate. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB00873; Loteprednol Etabonate. DR DrugBank; DB00959; Methylprednisolone. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB00764; Mometasone. DR DrugBank; DB00635; Prednisone. DR NextBio; 11517; -. DR ArrayExpress; P04150; -. DR Bgee; P04150; -. DR CleanEx; HS_NR3C1; -. DR GermOnline; ENSG00000113580; Homo sapiens. DR GO; GO:0005759; C:mitochondrial matrix; TAS:ProtInc. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0004883; F:glucocorticoid receptor activity; TAS:ProtInc. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0005496; F:steroid binding; IEA:UniProtKB-KW. DR GO; GO:0003700; F:transcription factor activity; TAS:ProtInc. DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW. DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; IEA:UniProtKB-KW. DR GO; GO:0051789; P:response to protein stimulus; IDA:MGI. DR GO; GO:0007530; P:sex determination; IEA:UniProtKB-KW. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; TAS:ProtInc. DR InterPro; IPR001409; Glcrtcd_rcpt. DR InterPro; IPR008946; Nucl_hormone_rcpt_ligand-bd. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd_core. DR InterPro; IPR001723; Str_hrmn_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR Gene3D; G3DSA:1.10.565.10; Nucl_hrmn_rcpt_lig_bd; 1. DR Gene3D; G3DSA:3.30.50.10; Znf_NHR/GATA; 1. DR Pfam; PF02155; GCR; 1. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00528; GLCORTICOIDR. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR ProDom; PD000035; Znf_C4steroid; 1. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 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; Alternative initiation; Alternative splicing; KW Chromatin regulator; Complete proteome; Cytoplasm; Disease mutation; KW DNA-binding; Isopeptide bond; Lipid-binding; Metal-binding; Nucleus; KW Phosphoprotein; Polymorphism; Pseudohermaphroditism; Receptor; KW Steroid-binding; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 777 Glucocorticoid receptor. FT /FTId=PRO_0000019937. FT DNA_BIND 421 486 Nuclear receptor. FT ZN_FING 421 441 NR C4-type. FT ZN_FING 457 481 NR C4-type. FT REGION 1 420 Modulating. FT REGION 487 527 Hinge. FT REGION 528 777 Steroid-binding. FT COMPBIAS 399 418 Glu/Pro/Ser/Thr-rich (PEST region). FT MOD_RES 8 8 Phosphothreonine. FT MOD_RES 45 45 Phosphoserine. FT MOD_RES 113 113 Phosphoserine (By similarity). FT MOD_RES 134 134 Phosphoserine. FT MOD_RES 141 141 Phosphoserine (By similarity). FT MOD_RES 203 203 Phosphoserine. FT MOD_RES 211 211 Phosphoserine. FT MOD_RES 226 226 Phosphoserine. FT MOD_RES 234 234 Phosphoserine. FT MOD_RES 267 267 Phosphoserine. FT CROSSLNK 277 277 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 293 293 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 419 419 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin) FT (Probable). FT VAR_SEQ 1 26 Missing (in isoform Alpha-B and isoform FT Beta-B). FT /FTId=VSP_018773. FT VAR_SEQ 451 451 G -> GR (in isoform Alpha-2 and isoform FT Beta-2). FT /FTId=VSP_007363. FT VAR_SEQ 491 674 Missing (in isoform GR-A alpha and FT isoform GR-A beta). FT /FTId=VSP_013340. FT VAR_SEQ 728 777 VVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGN FT IKKLLFHQK -> NVMWLKPESTSHTLI (in isoform FT Beta, isoform Beta-B, isoform Beta-2 and FT isoform GR-A beta). FT /FTId=VSP_003703. FT VARIANT 23 23 R -> K (in dbSNP:rs6190). FT /FTId=VAR_014140. FT VARIANT 29 29 F -> L. FT /FTId=VAR_015628. FT VARIANT 65 65 F -> V (in dbSNP:rs6192). FT /FTId=VAR_014622. FT VARIANT 112 112 L -> F. FT /FTId=VAR_015629. FT VARIANT 233 233 D -> N. FT /FTId=VAR_015630. FT VARIANT 363 363 N -> S (may increase sensitivity to FT exogenously administered glucocorticoids; FT may contribute to central obesity in men FT and show lack of association with other FT risk factors for coronary heart disease FT and diabetes mellitus; dbSNP:rs6195). FT /FTId=VAR_004675. FT VARIANT 421 421 C -> Y (in a glucocorticoid resistant FT leukemia cell line). FT /FTId=VAR_015631. FT VARIANT 477 477 R -> H (in glucocorticoid resistance). FT /FTId=VAR_013472. FT VARIANT 559 559 I -> N (in glucocorticoid resistance; FT interferes with translocation to the FT nucleus and thereby strongly reduces FT transcription activation. Is equally FT impaired in nuclear export. Acts as FT dominant negative mutant). FT /FTId=VAR_015632. FT VARIANT 571 571 V -> A (in pseudohermaphroditism; female FT with hypokalemia due to glucocorticoid FT resistance; 6-fold reduction in binding FT affinity compared with the wild-type FT receptor). FT /FTId=VAR_025014. FT VARIANT 641 641 D -> V (in glucocorticoid resistance). FT /FTId=VAR_004676. FT VARIANT 679 679 G -> S (in glucocorticoid resistance; has FT 50% binding affinity). FT /FTId=VAR_013473. FT VARIANT 729 729 V -> I (in glucocorticoid resistance). FT /FTId=VAR_004677. FT VARIANT 747 747 I -> M (in glucocorticoid resistance; FT alters interaction with NCOA2 and FT strongly reduces transcription FT activation; acts as dominant negative FT mutant). FT /FTId=VAR_015633. FT VARIANT 753 753 L -> F (in two glucocorticoid resistant FT leukemia cell lines lacking the normal FT allele). FT /FTId=VAR_004678. FT MUTAGEN 1 1 M->T: Abolishes expression of A-type FT isoforms. FT MUTAGEN 27 27 M->T: Abolishes expression of B-type FT isoforms. FT MUTAGEN 191 191 F->D: Reduces transactivation by the ADA FT complex. FT MUTAGEN 193 193 I->D: Reduces transactivation by the ADA FT complex. FT MUTAGEN 194 194 L->A: Strongly reduces transactivation by FT the ADA complex; when associated with V- FT 224 and F-225. FT MUTAGEN 197 197 L->E: Reduces transactivation by the ADA FT complex. FT MUTAGEN 213 213 W->A: Strongly reduces transactivation by FT the ADA complex. FT MUTAGEN 224 224 L->V: Strongly reduces transactivation by FT the ADA complex; when associated with A- FT 194 and F-225. FT MUTAGEN 225 225 L->F: Strongly reduces transactivation by FT the ADA complex; when associated with A- FT 194 and V-224. FT MUTAGEN 235 235 F->L: Strongly reduces transactivation by FT the ADA complex; when associated with V- FT 236. FT MUTAGEN 236 236 L->V: Strongly reduces transactivation by FT the ADA complex; when associated with L- FT 235. FT MUTAGEN 277 277 K->R: Strongly reduces sumoylation. FT Almost complete loss of sumoylation; when FT associated with R-293. FT MUTAGEN 293 293 K->R: Strongly reduces sumoylation. FT Almost complete loss of sumoylation; when FT associated with R-277. FT MUTAGEN 585 585 R->A: Reduces activation mediated by FT ligand binding domain; when associated FT with A-590. FT MUTAGEN 590 590 D->A: Reduces activation mediated by FT ligand binding domain; when associated FT with A-585. FT MUTAGEN 602 602 F->S: Increases solubility. No effect on FT transactivation by dexamethasone. FT MUTAGEN 625 625 P->A: Decreases transactivation by FT dexamethasone by 95%. FT MUTAGEN 628 628 I->A: Decreases dimerization and FT transactivation by dexamethasone; when FT associated with S-602. FT MUTAGEN 703 703 K->R: Slightly reduces sumoylation. FT CONFLICT 399 399 R -> G (in Ref. 4; BAD97314). FT CONFLICT 754 754 A -> T (in Ref. 4; BAD97314). FT TURN 525 527 FT HELIX 532 539 FT HELIX 556 578 FT HELIX 584 586 FT HELIX 589 616 FT STRAND 619 624 FT STRAND 627 629 FT HELIX 633 635 FT HELIX 639 655 FT HELIX 660 671 FT STRAND 673 676 FT HELIX 683 704 FT HELIX 709 732 FT STRAND 735 739 FT HELIX 740 746 FT HELIX 749 757 FT STRAND 769 771 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 //