GCR_MOUSE
ID GCR_MOUSE Reviewed; 792 AA.
AC P06537; E0ZPU5; E9PUR6; E9PYV1; Q06VW2; Q3U126; Q3U2M7; Q61628; Q61629;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Glucocorticoid receptor;
DE Short=GR;
DE AltName: Full=Nuclear receptor subfamily 3 group C member 1;
GN Name=Nr3c1; Synonyms=Grl, Grl1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT 78-GLN--GLN-86 DEL.
RX PubMed=3780669; DOI=10.1002/j.1460-2075.1986.tb04529.x;
RA Danielsen M., Northrop J.P., Ringold G.M.;
RT "The mouse glucocorticoid receptor: mapping of functional domains by
RT cloning, sequencing and expression of wild-type and mutant receptor
RT proteins.";
RL EMBO J. 5:2513-2522(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-91 DEL, AND
RP POLYMORPHISM.
RX PubMed=17012242; DOI=10.1096/fj.06-5926fje;
RA Xu D., Buehner A., Xu J., Lambert T., Nekl C., Nielsen M.K., Zhou Y.;
RT "A polymorphic glucocorticoid receptor in a mouse population may explain
RT inherited altered stress response and increased anxiety-type behaviors.";
RL FASEB J. 20:2414-2416(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, INDUCTION, AND VARIANT 78-GLN--GLN-86 DEL.
RX PubMed=20660300; DOI=10.1210/me.2009-0411;
RA Hinds T.D. Jr., Ramakrishnan S., Cash H.A., Stechschulte L.A., Heinrich G.,
RA Najjar S.M., Sanchez E.R.;
RT "Discovery of glucocorticoid receptor-beta in mice with a role in
RT metabolism.";
RL Mol. Endocrinol. 24:1715-1727(2010).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP 78-GLN--GLN-86 DEL.
RC STRAIN=NOD;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP 78-GLN--GLN-86 DEL.
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-764 (ISOFORMS 1 AND 2).
RX PubMed=2911477; DOI=10.1093/nar/17.1.445;
RA Nohno T., Kasai Y., Saito T.;
RT "Novel cDNA sequence possibly generated by alternative splicing of a mouse
RT glucocorticoid receptor gene transcript from Shionogi carcinoma 115.";
RL Nucleic Acids Res. 17:445-445(1989).
RN [8]
RP GLUCOCORTICOID-MEDIATED DOWN-REGULATION.
RX PubMed=2702670;
RA Vedeckis W.V., Ali M., Allen H.R.;
RT "Regulation of glucocorticoid receptor protein and mRNA levels.";
RL Cancer Res. 49:2295-2302(1989).
RN [9]
RP PHOSPHORYLATION AT SER-131; SER-159; THR-168; SER-221; SER-229; SER-243 AND
RP SER-324.
RX PubMed=2019585; DOI=10.1016/s0021-9258(20)89482-4;
RA Bodwell J.E., Orti E., Coull J.M., Pappin D.J.C., Smith L.I., Swift F.;
RT "Identification of phosphorylated sites in the mouse glucocorticoid
RT receptor.";
RL J. Biol. Chem. 266:7549-7555(1991).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH NR3C1 AND FKBP4; PPID; PPP5C OR STIP1.
RX PubMed=9195923; DOI=10.1074/jbc.272.26.16224;
RA Silverstein A.M., Galigniana M.D., Chen M.S., Owens-Grillo J.K.,
RA Chinkers M., Pratt W.B.;
RT "Protein phosphatase 5 is a major component of glucocorticoid
RT receptor.hsp90 complexes with properties of an FK506-binding
RT immunophilin.";
RL J. Biol. Chem. 272:16224-16230(1997).
RN [11]
RP INTERACTION WITH STAT5A AND STAT5B.
RX PubMed=9528750; DOI=10.1128/mcb.18.4.1783;
RA Cella N., Groner B., Hynes N.E.;
RT "Characterization of Stat5a and Stat5b homodimers and heterodimers and
RT their association with the glucocortiocoid receptor in mammary cells.";
RL Mol. Cell. Biol. 18:1783-1792(1998).
RN [12]
RP INTERACTION WITH TRIM28.
RX PubMed=9742105; DOI=10.1128/mcb.18.10.5880;
RA Chang C.J., Chen Y.L., Lee S.C.;
RT "Coactivator TIF1beta interacts with transcription factor C/EBPbeta and
RT glucocorticoid receptor to induce alpha1-acid glycoprotein gene
RT expression.";
RL Mol. Cell. Biol. 18:5880-5887(1998).
RN [13]
RP INTERACTION WITH TGFB1I1.
RX PubMed=10848625; DOI=10.1091/mbc.11.6.2007;
RA Yang L., Guerrero J., Hong H., DeFranco D.B., Stallcup M.R.;
RT "Interaction of the tau2 transcriptional activation domain of
RT glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5,
RT which localizes to both focal adhesions and the nuclear matrix.";
RL Mol. Biol. Cell 11:2007-2018(2000).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10678832; DOI=10.1126/science.287.5456.1262;
RA McNally J.G., Mueller W.G., Walker D., Wolford R., Hager G.L.;
RT "The glucocorticoid receptor: rapid exchange with regulatory sites in
RT living cells.";
RL Science 287:1262-1265(2000).
RN [15]
RP SUBCELLULAR LOCATION, HETEROMULTIMERIC COMPLEX FORMATION, INTERACTION WITH
RP FKBP4, AND MECHANISM OF TRANSLOCATION TO THE NUCLEUS.
RX PubMed=11278753; DOI=10.1074/jbc.m010809200;
RA Galigniana M.D., Radanyi C., Renoir J.-M., Housley P.R., Pratt W.B.;
RT "Evidence that the peptidylprolyl isomerase domain of the hsp90-binding
RT immunophilin FKBP52 is involved in both dynein interaction and
RT glucocorticoid receptor movement to the nucleus.";
RL J. Biol. Chem. 276:14884-14889(2001).
RN [16]
RP UBIQUITINATION AT LYS-435, MUTAGENESIS OF LYS-435, AND
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 [17]
RP ALTERNATIVE INITIATION, AND MUTAGENESIS OF MET-1 AND MET-28.
RX PubMed=11435610; DOI=10.1210/mend.15.7.0667;
RA Yudt M.R., Cidlowski J.A.;
RT "Molecular identification and characterization of A and B forms of the
RT glucocorticoid receptor.";
RL Mol. Endocrinol. 15:1093-1103(2001).
RN [18]
RP HETEROMULTIMERIC COMPLEX FORMATION, AND MECHANISM OF TRANSLOCATION TO THE
RP NUCLEUS.
RX PubMed=11751894; DOI=10.1074/jbc.c100531200;
RA Davies T.H., Ning Y.M., Sanchez E.R.;
RT "A new first step in activation of steroid receptors: hormone-induced
RT switching of FKBP51 and FKBP52 immunophilins.";
RL J. Biol. Chem. 277:4597-4600(2002).
RN [19]
RP INVOLVEMENT IN IMMUNE SYSTEM DEVELOPMENT.
RX PubMed=12949501; DOI=10.1038/nm895;
RA Brewer J.A., Khor B., Vogt S.K., Muglia L.M., Fujiwara H., Haegele K.E.,
RA Sleckman B.P., Muglia L.J.;
RT "T-cell glucocorticoid receptor is required to suppress COX-2-mediated
RT lethal immune activation.";
RL Nat. Med. 9:1318-1322(2003).
RN [20]
RP POSSIBLE FUNCTION IN THE CONTROL OF BODY GROWTH.
RX PubMed=15037546; DOI=10.1101/gad.284704;
RA Tronche F., Opherk C., Moriggl R., Kellendonk C., Reimann A., Schwake L.,
RA Reichardt H.M., Stangl K., Gau D., Hoeflich A., Beug H., Schmid W.,
RA Schuetz G.;
RT "Glucocorticoid receptor function in hepatocytes is essential to promote
RT postnatal body growth.";
RL Genes Dev. 18:492-497(2004).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, and
RC Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP FUNCTION IN ADIPOGENESIS, INTERACTION WITH FKBP5 AND PPP5C, PHOSPHORYLATION
RP AT SER-221; SER-229 AND SER-243, AND DEPHOSPHORYLATION AT SER-221 AND
RP SER-243 BY PPP5C.
RX PubMed=21994940; DOI=10.1074/jbc.m111.311662;
RA Hinds T.D. Jr., Stechschulte L.A., Cash H.A., Whisler D., Banerjee A.,
RA Yong W., Khuder S.S., Kaw M.K., Shou W., Najjar S.M., Sanchez E.R.;
RT "Protein phosphatase 5 mediates lipid metabolism through reciprocal control
RT of glucocorticoid receptor and peroxisome proliferator-activated receptor-?
RT (PPAR?).";
RL J. Biol. Chem. 286:42911-42922(2011).
RN [23]
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 [24]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-24, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [25]
RP INTERACTION WITH CIART.
RX PubMed=24736997; DOI=10.1371/journal.pbio.1001839;
RA Goriki A., Hatanaka F., Myung J., Kim J.K., Yoritaka T., Tanoue S., Abe T.,
RA Kiyonari H., Fujimoto K., Kato Y., Todo T., Matsubara A., Forger D.,
RA Takumi T.;
RT "A novel protein, CHRONO, functions as a core component of the mammalian
RT circadian clock.";
RL PLoS Biol. 12:E1001839-E1001839(2014).
RN [26]
RP FUNCTION.
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 [27]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-493.
RX PubMed=25676786; DOI=10.1016/j.steroids.2015.01.022;
RA Banuelos J., Shin S.C., Lu N.Z.;
RT "A hotspot in the glucocorticoid receptor DNA-binding domain susceptible to
RT loss of function mutation.";
RL Steroids 96:115-120(2015).
RN [28]
RP INTERACTION WITH CRY1 AND CRY2.
RX PubMed=28751364; DOI=10.1073/pnas.1704955114;
RA Kriebs A., Jordan S.D., Soto E., Henriksson E., Sandate C.R., Vaughan M.E.,
RA Chan A.B., Duglan D., Papp S.J., Huber A.L., Afetian M.E., Yu R.T.,
RA Zhao X., Downes M., Evans R.M., Lamia K.A.;
RT "Circadian repressors CRY1 and CRY2 broadly interact with nuclear receptors
RT and modulate transcriptional activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:8776-8781(2017).
RN [29]
RP INTERACTION WITH HSP90AA1 AND HSP90AB1, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=27686098; DOI=10.1242/jcs.190959;
RA Okabe T., Chavan R., Fonseca Costa S.S., Brenna A., Ripperger J.A.,
RA Albrecht U.;
RT "REV-ERBalpha influences the stability and nuclear localization of the
RT glucocorticoid receptor.";
RL J. Cell Sci. 129:4143-4154(2016).
CC -!- FUNCTION: Receptor for glucocorticoids (GC). Has a dual mode of action:
CC as a transcription factor that binds to glucocorticoid response
CC elements (GRE), both for nuclear and mitochondrial DNA, and as a
CC modulator of other transcription factors. Affects inflammatory
CC responses, cellular proliferation and differentiation in target
CC tissues. Involved in chromatin remodeling (PubMed:10678832). Plays a
CC role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs
CC and interacting with PNRC2 in a ligand-dependent manner which recruits
CC the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to
CC RNA decay (By similarity). Could act as a coactivator for STAT5-
CC dependent transcription upon growth hormone (GH) stimulation and could
CC reveal an essential role of hepatic GR in the control of body growth
CC (PubMed:15037546). {ECO:0000250|UniProtKB:P04150,
CC ECO:0000269|PubMed:10678832, ECO:0000269|PubMed:15037546}.
CC -!- FUNCTION: [Isoform 1]: Has transcriptional activation and repression
CC activity (By similarity). Mediates glucocorticoid-induced apoptosis (By
CC similarity). Promotes accurate chromosome segregation during mitosis
CC (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May
CC play a negative role in adipogenesis through the regulation of
CC lipolytic and antilipogenic gene expression (PubMed:21994940).
CC {ECO:0000250|UniProtKB:P04150, ECO:0000269|PubMed:21994940,
CC ECO:0000269|PubMed:25847991}.
CC -!- FUNCTION: [Isoform 3]: Acts as a dominant negative inhibitor of isoform
CC 1 (PubMed:20660300). Has intrinsic transcriptional activity independent
CC of isoform Alpha when both isoforms are coexpressed (By similarity).
CC Loses this transcription modulator function on its own (By similarity).
CC Has no hormone-binding activity (PubMed:20660300). May play a role in
CC controlling glucose metabolism by maintaining insulin sensitivity
CC (PubMed:20660300). Reduces hepatic gluconeogenesis through down-
CC regulation of PEPCK in an isoform Alpha-dependent manner (By
CC similarity). Directly regulates STAT1 expression in isoform Alpha-
CC independent manner (By similarity). {ECO:0000250|UniProtKB:P04150,
CC ECO:0000269|PubMed:20660300}.
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:9195923, PubMed:21994940).
CC Upon ligand binding FKBP5 dissociates from the complex and FKBP4 takes
CC its place, thereby linking the complex to dynein and mediating
CC transport to the nucleus, where the complex dissociates
CC (PubMed:9195923, PubMed:11278753). Probably forms a complex composed of
CC chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client
CC protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain
CC co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Directly
CC interacts with UNC45A (By similarity). Binds to DNA as a homodimer, and
CC as heterodimer with NR3C2 or the retinoid X receptor. Binds STAT5A and
CC STAT5B homodimers and heterodimers (PubMed:9528750). Interacts with
CC NRIP1, POU2F1, POU2F2 and TRIM28 (PubMed:9742105). Interacts with
CC several coactivator complexes, including the SMARCA4 complex,
CC CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2
CC and NCOA6 (By similarity). Interaction with BAG1 inhibits
CC transactivation (By similarity). Interacts with HEXIM1 and TGFB1I1
CC (PubMed:10848625). Interacts with NCOA1 (By similarity). 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:22170608, PubMed:28751364). Interacts with CIART
CC (PubMed:24736997). Interacts with RWDD3 (By similarity). Interacts with
CC UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3
CC (By similarity). Interacts with GRIP1 (By similarity). Interacts with
CC NR4A3 (via nuclear receptor DNA-binding domain), represses
CC transcription activity of NR4A3 on the POMC promoter Nur response
CC element (NurRE) (By similarity). Directly interacts with PNRC2 to
CC attract and form a complex with UPF1 and DCP1A; the interaction leads
CC to rapid mRNA degradation (By similarity). Interacts with GSK3B (By
CC similarity). Interacts with FNIP1 and FNIP2 (By similarity). Interacts
CC (via C-terminus) with HNRNPU (via C-terminus) (By similarity).
CC Interacts with MCM3AP (By similarity). Interacts (via domain NR LBD)
CC with HSP90AA1 and HSP90AB1 (PubMed:27686098). In the absence of
CC hormonal ligand, interacts with TACC1 (By similarity).
CC {ECO:0000250|UniProtKB:P04150, ECO:0000250|UniProtKB:P06536,
CC ECO:0000269|PubMed:10678832, ECO:0000269|PubMed:10848625,
CC ECO:0000269|PubMed:11278753, ECO:0000269|PubMed:21994940,
CC ECO:0000269|PubMed:22170608, ECO:0000269|PubMed:24736997,
CC ECO:0000269|PubMed:27686098, ECO:0000269|PubMed:28751364,
CC ECO:0000269|PubMed:9195923, ECO:0000269|PubMed:9528750,
CC ECO:0000269|PubMed:9742105}.
CC -!- INTERACTION:
CC P06537; O88485: Dync1i1; NbExp=2; IntAct=EBI-492753, EBI-492834;
CC P06537; P30416: Fkbp4; NbExp=3; IntAct=EBI-492753, EBI-492746;
CC P06537; Q64378: Fkbp5; NbExp=2; IntAct=EBI-492753, EBI-492796;
CC P06537; P11499: Hsp90ab1; NbExp=2; IntAct=EBI-492753, EBI-492813;
CC P06537-1; P97784: Cry1; NbExp=3; IntAct=EBI-15959147, EBI-1266607;
CC P06537-1; Q9R194: Cry2; NbExp=3; IntAct=EBI-15959147, EBI-1266619;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11278753,
CC ECO:0000269|PubMed:25676786, ECO:0000269|PubMed:27686098}. Nucleus
CC {ECO:0000269|PubMed:10678832, ECO:0000269|PubMed:11278753,
CC ECO:0000269|PubMed:25676786, ECO:0000269|PubMed:27686098}.
CC Note=Cytoplasmic in the absence of ligand, nuclear after ligand-binding
CC (PubMed:11278753). The hormone-occupied receptor undergoes rapid
CC exchange between chromatin and the nucleoplasmic compartment
CC (PubMed:10678832). In the presence of NR1D1 shows a time-dependent
CC subcellular localization, localizing to the cytoplasm at ZT8 and to the
CC nucleus at ZT20 (PubMed:27686098). Lacks this diurnal pattern of
CC localization in the absence of NR1D1, localizing to both nucleus and
CC the cytoplasm at ZT8 and ZT20 (PubMed:27686098).
CC {ECO:0000269|PubMed:10678832, ECO:0000269|PubMed:11278753,
CC ECO:0000269|PubMed:27686098}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm
CC {ECO:0000250|UniProtKB:P04150}. Nucleus {ECO:0000250|UniProtKB:P04150}.
CC Mitochondrion {ECO:0000250|UniProtKB:P04150}. Cytoplasm, cytoskeleton,
CC spindle {ECO:0000250|UniProtKB:P04150}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:P04150}. Note=After ligand activation,
CC translocates from the cytoplasm to the nucleus.
CC {ECO:0000250|UniProtKB:P04150}.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus
CC {ECO:0000269|PubMed:20660300}. Cytoplasm {ECO:0000269|PubMed:20660300}.
CC Note=Expressed predominantly in the nucleus with some expression also
CC detected in the cytoplasm. {ECO:0000269|PubMed:20660300}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=5;
CC Name=1; Synonyms=1-A, GR form A, Alpha;
CC IsoId=P06537-1; Sequence=Displayed;
CC Name=2; Synonyms=2-A, GR form B, Gamma;
CC IsoId=P06537-2; Sequence=VSP_003704;
CC Name=1-B;
CC IsoId=P06537-3; Sequence=VSP_018774;
CC Name=2-B;
CC IsoId=P06537-4; Sequence=VSP_018774, VSP_003704;
CC Name=3; Synonyms=Beta;
CC IsoId=P06537-5; Sequence=VSP_058320, VSP_058321;
CC -!- TISSUE SPECIFICITY: Expressed in spleen, kidney and liver
CC (PubMed:20660300). Expressed in a circadian manner in the liver
CC (PubMed:27686098). {ECO:0000269|PubMed:20660300,
CC ECO:0000269|PubMed:27686098}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed at highest level in spleen
CC with lesser amounts in kidney and liver. {ECO:0000269|PubMed:20660300}.
CC -!- INDUCTION: [Isoform 1]: Down-regulated by glucocorticoids.
CC {ECO:0000269|PubMed:20660300}.
CC -!- INDUCTION: [Isoform 3]: Up-regulated by glucocorticoids and insulin.
CC {ECO:0000269|PubMed:20660300}.
CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, a
CC DNA-binding domain and a C-terminal ligand-binding domain. The ligand-
CC binding domain is required for correct chromosome segregation during
CC mitosis although ligand binding is not required.
CC {ECO:0000250|UniProtKB:P04150}.
CC -!- PTM: Acetylation by CLOCK reduces its binding to glucocorticoid
CC response elements and its transcriptional activity.
CC {ECO:0000250|UniProtKB:P04150}.
CC -!- PTM: Increased proteasome-mediated degradation in response to
CC glucocorticoids. {ECO:0000269|PubMed:11555652}.
CC -!- PTM: Phosphorylated in the absence of hormone; becomes
CC hyperphosphorylated in the presence of glucocorticoids. Phosphorylated
CC in the absence of hormone; becomes hyperphosphorylated in the presence
CC of glucocorticoid. The Ser-221, Ser-243 and Ser-421-phosphorylated
CC forms are mainly cytoplasmic, and the Ser-229-phosphorylated form is
CC nuclear (By similarity). Phosphorylation at Ser-229 increases
CC transcriptional activity (By similarity). Phosphorylation at Ser-221,
CC Ser-243 and Ser-421 decreases signaling capacity (By similarity).
CC Phosphorylation at Ser-421 may protect from glucocorticoid-induced
CC apoptosis (By similarity). Phosphorylation at Ser-221 and Ser-229 is
CC not required in regulation of chromosome segregation (By similarity).
CC May be dephosphorylated by PPP5C, attenuates NR3C1 action
CC (PubMed:21994940). {ECO:0000250|UniProtKB:P04150,
CC ECO:0000269|PubMed:2019585, ECO:0000269|PubMed:21994940}.
CC -!- PTM: Sumoylation at Lys-294 and Lys-310 negatively regulates its
CC transcriptional activity. Sumoylation at Lys-718 positively regulates
CC its transcriptional activity in the presence of RWDD3. Sumoylation at
CC Lys-294 and Lys-310 is dispensable whereas sumoylation at Lys-718 is
CC critical for the stimulatory effect of RWDD3 on its transcriptional
CC activity. Heat shock increases sumoylation in a RWDD3-dependent manner.
CC {ECO:0000250|UniProtKB:P06536}.
CC -!- PTM: Ubiquitinated; restricts glucocorticoid-mediated transcriptional
CC signaling. {ECO:0000269|PubMed:11555652}.
CC -!- POLYMORPHISM: The poly-Gln region in 78-91 is polymorphic
CC (PubMed:3780669, PubMed:17012242, PubMed:20660300, PubMed:16141072,
CC PubMed:15489334). Polymorphism plays a role in complex mechanisms
CC leading to lower corticosterone response to stress, and may also be
CC associated with decreased locomotive and increased anxiety-type
CC behaviors (PubMed:17012242). {ECO:0000269|PubMed:15489334,
CC ECO:0000269|PubMed:16141072, ECO:0000269|PubMed:17012242,
CC ECO:0000269|PubMed:20660300, ECO:0000269|PubMed:3780669}.
CC -!- MISCELLANEOUS: T-cell is a critical cellular target of GR, as immune
CC activation in mice lacking GR resulted in significant mortality. This
CC lethal activation is rescued by PTGS2 inhibition but not steroid
CC administration or cytokine neutralization.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 1-B]: Produced by alternative initiation at
CC Met-28 of isoform 1. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 2-B]: Produced by alternative initiation at
CC Met-28 of isoform 2. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR3
CC subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; X04435; CAA28031.1; -; mRNA.
DR EMBL; DQ504162; ABF57998.1; -; mRNA.
DR EMBL; HM236293; ADM18962.1; -; mRNA.
DR EMBL; AK155200; BAE33113.1; -; mRNA.
DR EMBL; AK156323; BAE33674.1; -; mRNA.
DR EMBL; GL456180; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC129912; AAI29913.1; -; mRNA.
DR EMBL; BC129913; AAI29914.1; -; mRNA.
DR EMBL; X13358; CAA31738.1; -; mRNA.
DR EMBL; X13359; CAA31739.1; -; mRNA.
DR CCDS; CCDS37791.1; -. [P06537-1]
DR PIR; A25691; A25691.
DR RefSeq; NP_032199.3; NM_008173.3. [P06537-1]
DR RefSeq; XP_006525721.1; XM_006525658.1. [P06537-2]
DR RefSeq; XP_006525722.1; XM_006525659.3. [P06537-2]
DR RefSeq; XP_006525723.1; XM_006525660.2. [P06537-2]
DR RefSeq; XP_006525724.1; XM_006525661.2. [P06537-2]
DR RefSeq; XP_006525725.1; XM_006525662.1. [P06537-2]
DR RefSeq; XP_006525726.1; XM_006525663.3. [P06537-2]
DR RefSeq; XP_006525727.1; XM_006525664.1. [P06537-2]
DR RefSeq; XP_006525728.1; XM_006525665.3. [P06537-2]
DR RefSeq; XP_006525729.1; XM_006525666.3.
DR RefSeq; XP_017173324.1; XM_017317835.1.
DR RefSeq; XP_017173325.1; XM_017317836.1.
DR RefSeq; XP_017173326.1; XM_017317837.1.
DR RefSeq; XP_017173327.1; XM_017317838.1.
DR PDB; 3MNE; X-ray; 1.96 A; A=536-792.
DR PDB; 3MNO; X-ray; 1.55 A; A=536-792.
DR PDB; 3MNP; X-ray; 1.50 A; A=536-792.
DR PDBsum; 3MNE; -.
DR PDBsum; 3MNO; -.
DR PDBsum; 3MNP; -.
DR AlphaFoldDB; P06537; -.
DR SMR; P06537; -.
DR CORUM; P06537; -.
DR DIP; DIP-11N; -.
DR IntAct; P06537; 12.
DR MINT; P06537; -.
DR STRING; 10090.ENSMUSP00000095199; -.
DR BindingDB; P06537; -.
DR ChEMBL; CHEMBL3144; -.
DR DrugCentral; P06537; -.
DR GuidetoPHARMACOLOGY; 625; -.
DR iPTMnet; P06537; -.
DR PhosphoSitePlus; P06537; -.
DR SwissPalm; P06537; -.
DR EPD; P06537; -.
DR jPOST; P06537; -.
DR MaxQB; P06537; -.
DR PaxDb; P06537; -.
DR PeptideAtlas; P06537; -.
DR PRIDE; P06537; -.
DR ProteomicsDB; 271197; -. [P06537-1]
DR ProteomicsDB; 271198; -. [P06537-2]
DR ProteomicsDB; 271199; -. [P06537-3]
DR ProteomicsDB; 271200; -. [P06537-4]
DR ProteomicsDB; 271201; -. [P06537-5]
DR ProteomicsDB; 333325; -.
DR ProteomicsDB; 355014; -.
DR Antibodypedia; 1329; 1342 antibodies from 44 providers.
DR DNASU; 14815; -.
DR Ensembl; ENSMUST00000025300; ENSMUSP00000025300; ENSMUSG00000024431. [P06537-1]
DR Ensembl; ENSMUST00000097592; ENSMUSP00000095199; ENSMUSG00000024431. [P06537-2]
DR Ensembl; ENSMUST00000115567; ENSMUSP00000111229; ENSMUSG00000024431. [P06537-1]
DR Ensembl; ENSMUST00000115571; ENSMUSP00000111233; ENSMUSG00000024431. [P06537-1]
DR GeneID; 14815; -.
DR KEGG; mmu:14815; -.
DR UCSC; uc008esx.1; mouse.
DR CTD; 2908; -.
DR MGI; MGI:95824; Nr3c1.
DR VEuPathDB; HostDB:ENSMUSG00000024431; -.
DR eggNOG; KOG3575; Eukaryota.
DR GeneTree; ENSGT00940000156385; -.
DR HOGENOM; CLU_020317_0_0_1; -.
DR InParanoid; P06537; -.
DR OMA; NLPCMYD; -.
DR OrthoDB; 333292at2759; -.
DR TreeFam; TF106510; -.
DR Reactome; R-MMU-3371497; HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand.
DR Reactome; R-MMU-383280; Nuclear Receptor transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR BioGRID-ORCS; 14815; 0 hits in 78 CRISPR screens.
DR ChiTaRS; Nr3c1; mouse.
DR EvolutionaryTrace; P06537; -.
DR PRO; PR:P06537; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P06537; protein.
DR Bgee; ENSMUSG00000024431; Expressed in median eminence of neurohypophysis and 271 other tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0031072; F:heat shock protein binding; ISO:MGI.
DR GO; GO:0042562; F:hormone binding; ISO:MGI.
DR GO; GO:0030544; F:Hsp70 protein binding; ISO:MGI.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0004883; F:nuclear glucocorticoid receptor activity; IDA:MGI.
DR GO; GO:0004879; F:nuclear receptor activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:ARUK-UCL.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0005496; F:steroid binding; ISS:UniProtKB.
DR GO; GO:1990239; F:steroid hormone binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030325; P:adrenal gland development; IMP:MGI.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:MGI.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISO:MGI.
DR GO; GO:0071383; P:cellular response to steroid hormone stimulus; ISO:MGI.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:MGI.
DR GO; GO:0006338; P:chromatin remodeling; ISO:MGI.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISO:MGI.
DR GO; GO:0008211; P:glucocorticoid metabolic process; IMP:MGI.
DR GO; GO:0042921; P:glucocorticoid receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0030518; P:intracellular steroid hormone receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060603; P:mammary gland duct morphogenesis; IMP:MGI.
DR GO; GO:0042711; P:maternal behavior; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0031914; P:negative regulation of synaptic plasticity; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0043116; P:negative regulation of vascular permeability; ISO:MGI.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI.
DR GO; GO:2000324; P:positive regulation of glucocorticoid receptor signaling pathway; ISO:MGI.
DR GO; GO:0014049; P:positive regulation of glutamate secretion; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IDA:BHF-UCL.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0031946; P:regulation of glucocorticoid biosynthetic process; IMP:MGI.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IMP:MGI.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISO:MGI.
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:CAFA.
DR GO; GO:0046685; P:response to arsenic-containing substance; ISO:MGI.
DR Gene3D; 1.10.565.10; -; 1.
DR Gene3D; 3.30.50.10; -; 1.
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 Chromatin regulator; Cytoplasm; Cytoskeleton; DNA-binding; Isopeptide bond;
KW Lipid-binding; Metal-binding; Methylation; Mitochondrion; Nucleus;
KW Phosphoprotein; Receptor; Reference proteome; Steroid-binding;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..792
FT /note="Glucocorticoid receptor"
FT /id="PRO_0000019939"
FT DOMAIN 539..773
FT /note="NR LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01189"
FT DNA_BIND 434..509
FT /note="Nuclear receptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 437..457
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT ZN_FING 473..497
FT /note="NR C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00407"
FT REGION 1..436
FT /note="Modulating"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 67..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 148..201
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..792
FT /note="Interaction with CLOCK"
FT /evidence="ECO:0000250"
FT REGION 503..538
FT /note="Hinge"
FT REGION 547..712
FT /note="Interaction with CRY1"
FT /evidence="ECO:0000250"
FT MOD_RES 24
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 46
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 131
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2019585"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2019585"
FT MOD_RES 168
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:2019585"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2019585,
FT ECO:0000269|PubMed:21994940"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2019585,
FT ECO:0000269|PubMed:21994940"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2019585,
FT ECO:0000269|PubMed:21994940"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 324
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2019585"
FT MOD_RES 421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 496
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 508
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 510
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT MOD_RES 511
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 294
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 294
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 310
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 310
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000305|PubMed:11555652"
FT CROSSLNK 718
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:P04150"
FT VAR_SEQ 1..27
FT /note="Missing (in isoform 1-B and isoform 2-B)"
FT /evidence="ECO:0000305"
FT /id="VSP_018774"
FT VAR_SEQ 467
FT /note="G -> GR (in isoform 2 and isoform 2-B)"
FT /evidence="ECO:0000303|PubMed:2911477"
FT /id="VSP_003704"
FT VAR_SEQ 744..757
FT /note="VENLLSYCFQTFLD -> STKHKSKTTAKKKK (in isoform 3)"
FT /id="VSP_058320"
FT VAR_SEQ 758..792
FT /note="Missing (in isoform 3)"
FT /id="VSP_058321"
FT VARIANT 78..86
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:16141072, ECO:0000269|PubMed:20660300,
FT ECO:0000269|PubMed:3780669"
FT VARIANT 91
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:17012242"
FT MUTAGEN 1
FT /note="M->T: Abolishes expression of A-type isoforms."
FT /evidence="ECO:0000269|PubMed:11435610"
FT MUTAGEN 28
FT /note="M->T: Abolishes expression of B-type isoforms. 1-B."
FT /evidence="ECO:0000269|PubMed:11435610"
FT MUTAGEN 435
FT /note="K->A: Abolishes glucocorticoid-mediated degradation
FT and enhances transcription trans-activation."
FT /evidence="ECO:0000269|PubMed:11555652"
FT MUTAGEN 493
FT /note="R->A: Abolishes transactivation activity."
FT /evidence="ECO:0000269|PubMed:25676786"
FT MUTAGEN 493
FT /note="R->C: Abolishes transcriptional activity. Does not
FT impair ligand binding."
FT /evidence="ECO:0000269|PubMed:25676786"
FT MUTAGEN 493
FT /note="R->K: Does not change transactivation activity."
FT /evidence="ECO:0000269|PubMed:25676786"
FT CONFLICT 432
FT /note="P -> L (in Ref. 4; BAE33674)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="G -> V (in Ref. 1; CAA28031)"
FT /evidence="ECO:0000305"
FT CONFLICT 792
FT /note="K -> E (in Ref. 4; BAE33674)"
FT /evidence="ECO:0000305"
FT HELIX 547..554
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 571..594
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 599..601
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 604..631
FT /evidence="ECO:0007829|PDB:3MNP"
FT STRAND 634..639
FT /evidence="ECO:0007829|PDB:3MNP"
FT STRAND 642..644
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 646..649
FT /evidence="ECO:0007829|PDB:3MNP"
FT TURN 652..654
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 655..671
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 675..686
FT /evidence="ECO:0007829|PDB:3MNP"
FT STRAND 688..691
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 698..717
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 723..756
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 758..760
FT /evidence="ECO:0007829|PDB:3MNP"
FT HELIX 766..780
FT /evidence="ECO:0007829|PDB:3MNP"
FT STRAND 784..786
FT /evidence="ECO:0007829|PDB:3MNP"
SQ SEQUENCE 792 AA; 87164 MW; 528730BD2C517554 CRC64;
MDSKESLAPP GRDEVPSSLL GRGRGSVMDL YKTLRGGATV KVSASSPSVA AASQADSKQQ
RILLDFSKGS ASNAQQQQQQ QQQQQQQQQQ QPQPDLSKAV SLSMGLYMGE TETKVMGNDL
GYPQQGQLGL SSGETDFRLL EESIANLNRS TSRPENPKSS TPAAGCATPT EKEFPQTHSD
PSSEQQNRKS QPGTNGGSVK LYTTDQSTFD ILQDLEFSAG SPGKETNESP WRSDLLIDEN
LLSPLAGEDD PFLLEGDVNE DCKPLILPDT KPKIQDTGDT ILSSPSSVAL PQVKTEKDDF
IELCTPGVIK QEKLGPVYCQ ASFSGTNIIG NKMSAISVHG VSTSGGQMYH YDMNTASLSQ
QQDQKPVFNV IPPIPVGSEN WNRCQGSGED NLTSLGAMNF AGRSVFSNGY SSPGMRPDVS
SPPSSSSTAT GPPPKLCLVC SDEASGCHYG VLTCGSCKVF FKRAVEGQHN YLCAGRNDCI
IDKIRRKNCP ACRYRKCLQA GMNLEARKTK KKIKGIQQAT AGVSQDTSEN ANKTIVPAAL
PQLTPTLVSL LEVIEPEVLY AGYDSSVPDS AWRIMTTLNM LGGRQVIAAV KWAKAIPGFR
NLHLDDQMTL LQYSWMFLMA FALGWRSYRQ ASGNLLCFAP DLIINEQRMT LPCMYDQCKH
MLFISTELQR LQVSYEEYLC MKTLLLLSSV PKEGLKSQEL FDEIRMTYIK ELGKAIVKRE
GNSSQNWQRF YQLTKLLDSM HDVVENLLSY CFQTFLDKSM SIEFPEMLAE IITNQIPKYS
NGNIKKLLFH QK
