
AC   T00337
XX
ID   T00337
XX
DT   15.10.1992 (created); ewi.
DT   31.12.2014 (updated); ros.
CO   Copyright (C), QIAGEN.
XX
FA   GR-alpha
XX
SY   Alpha-A; glucocorticoid receptor; GR; GR alpha; NR3C1.
XX
OS   human, Homo sapiens
OC   eukaryota; animalia; metazoa; chordata; vertebrata; tetrapoda; mammalia; eutheria; primates
XX
GE   G000268 NR3C1; HGNC: NR3C1.
XX
CL   C0002; CC (rec); 2.1.1.1.1.1.
XX
SZ   777 AA; 85.7 kDa (cDNA) (calc.), 88-94 kDa (SDS)
XX
SQ   MDSKESLTPGREENPSSVLAQERGDVMDFYKTLRGGATVKVSASSPSLAVASQSDSKQRR
SQ   LLVDFPKGSVSNAQQPDLSKAVSLSMGLYMGETETKVMGNDLGFPQQGQISLSSGETDLK
SQ   LLEESIANLNRSTSVPENPKSSASTAVSAAPTEKEFPKTHSDVSSEQQHLKGQTGTNGGN
SQ   VKLYTTDQSTFDILQDLEFSSGSPGKETNESPWRSDLLIDENCLLSPLAGEDDSFLLEGN
SQ   SNEDCKPLILPDTKPKIKDNGDLVLSSPSNVTLPQVKTEKEDFIELCTPGVIKQEKLGTV
SQ   YCQASFPGANIIGNKMSAISVHGVSTSGGQMYHYDMNTASLSQQQDQKPIFNVIPPIPVG
SQ   SENWNRCQGSGDDNLTSLGTLNFPGRTVFSNGYSSPSMRPDVSSPPSSSSTATTGPPPKL
SQ   CLVCSDEASGCHYGVLTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRYRK
SQ   CLQAGMNLEARKTKKKIKGIQQATTGVSQETSENPGNKTIVPATLPQLTPTLVSLLEVIE
SQ   PEVLYAGYDSSVPDSTWRIMTTLNMLGGRQVIAAVKWAKAIPGFRNLHLDDQMTLLQYSW
SQ   MFLMAFALGWRSYRQSSANLLCFAPDLIINEQRMTLPCMYDQCKHMLYVSSELHRLQVSY
SQ   EEYLCMKTLLLLSSVPKDGLKSQELFDEIRMTYIKELGKAIVKREGNSSQNWQRFYQLTK
SQ   LLDSMHEVVENLLNYCFQTFLDKTMSIEFPEMLAEIITNQIPKYSNGNIKKLLFHQK
XX
SC   Swiss-Prot#P04150-1
XX
FT       26    401   
   PF02155; Glucocorticoid receptor.
FT       78    262   
   trans-activating domain (tau1) [20].
FT      187    285   
   amino-terminal activation function AF-1 [24].
FT      187    285   
   functional cooperation with STAT5 [24].
FT      261    595   
   PF00478; IMP dehydrogenase / GMP reductase domai.
FT      418    489   
   SM00399; c4gold.
FT      418    493   
   PS51030; NUCLEAR_REC_DBD_2.
FT      419    494   
   PF00105; Zinc finger, C4 type (two domains).
FT      421    486   
   region C, DNA-binding domain (DBD) [19].
FT      482    777   
   C-terminal ligand binding domain, LBD [24].
FT      526    556   
   trans-activating domain (tau2) [21].
FT      565    729   
   SM00430; holi.
FT      568    752   
   PF00104; Ligand-binding domain of nuclear hormon.
FT      748    762   
   AF-2 domain (transactivation activity) [23].
XX
SF   2 splice variants alpha T00337 and beta T01920 (742 AA), differing in their C-termini [8];
SF   the first zinc finger binds specifically to the GRE, the second enhances the affinity [11];
SF   AGRND within the second finger mediates homodimerization and contributes to the differential DNA-binding specificity against other nuclear receptors [14];
SF   G->E-variant (after 3rd Cys of the zinc finger region) recognizes GRE as well as ERE;
SF   AGRND -> KYEGK (between 1st Cys doublet of the 2nd zinc finger): conversion to a TRE-binding receptor;
SF   cooperative binding to a double GRE through tau1 domain;
XX
FF   activator or repressor in response to glucocorticoid hormones [10];
FF   binds hormone, translocates into the nucleus, and activates transcription of hormone-sensitive gene in contrast to beta isoform T01920 which does not activate known hormone-sensitive genes [8];
FF   cooperating with other transcription factors, it may act through composite elements [15] [22];
FF   can be inhibited by physical interaction with c-Jun or c-Fos [2] [1];
FF   represses Oct-1 DNA binding [16];
FF   leukemic cell lethality through DBD (1st zinc finger and 1/2 of second) [5];
FF   often provides glucocorticoid-dependent gene activation acting as a co-activator rather than a DNA-binding factor, may function as a co-activator for STAT5 [24];
XX
IN   T00029 AP-1; human, Homo sapiens.
IN   T00123 c-Fos; human, Homo sapiens.
IN   T00133 c-Jun; human, Homo sapiens.
IN   T06596 C/EBPbeta-LIP; human, Homo sapiens.
IN   T08300 ER-alpha-L; human, Homo sapiens.
IN   T00990 FKBP59; human, Homo sapiens.
IN   T00337 GR-alpha; human, Homo sapiens.
IN   T01920 GR-beta; human, Homo sapiens.
IN   T00993 hsp56; human, Homo sapiens.
IN   T00992 Hsp90; human, Homo sapiens.
IN   T01466 POU2F1; Chinese hamster (Gray hamster), Cricetulus griseus.
IN   T00644 POU2F1a; mouse, Mus musculus.
IN   T30113 Trx1; human, Homo sapiens.
XX
MX   M00205 V$GRE_C.
MX   M07355 V$GR_Q4.
MX   M00192 V$GR_Q6.
MX   M00921 V$GR_Q6_01.
MX   M01836 V$GR_Q6_02.
MX   M02219 V$NR3C1_01.
MX   M00960 V$PR_Q2.
XX
BS   R03199.
BS   R03526.
BS   R03530.
BS   R03531.
BS   R03561.
BS   R03562.
BS   R00973.
BS   R00974.
BS   R00975.
BS   R02163.
BS   R12350.
BS   R35593.
BS   R38869.
BS   R38870.
BS   R00591.
BS   R00593.
BS   R00595.
BS   R12328.
BS   R12329.
BS   R12330.
BS   R73928.
BS   R73929.
BS   R03551.
BS   R03552.
BS   R03555.
BS   R03556.
BS   R39686.
BS   R01480.
BS   R01481.
BS   R26402.
BS   R26403.
BS   R26405.
XX
DR   TRANSPATH: MO000019614.
DR   TRANSCOMPEL: C00130.
DR   PATHODB: MT010635.
DR   PATHODB: MT010647.
DR   PATHODB: MT010651.
DR   PATHODB: MT010652.
DR   PATHODB: MT010653.
DR   PATHODB: MT010654.
DR   PATHODB: MT010655.
DR   PATHODB: MT010658.
DR   PATHODB: MT010660.
DR   PATHODB: MT010677.
DR   PATHODB: MT010678.
DR   PATHODB: MT010679.
DR   EMBL: M10901; HSGCRA.
DR   EMBL: M73050; HSGRA1.
DR   EMBL: X03225; HSGCRAR.
DR   UniProtKB: P04150-1;
XX
RN   [1]; RE0000168.
RX   PUBMED: 2169351.
RA   Jonat C., Rahmsdorf H. J., Park K.-K., Cato A. C. B., Gebel S., Ponta H., Herrlich P.
RT   Antitumor promotion and antiinflammation: Down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone
RL   Cell 62:1189-1204 (1990).
RN   [2]; RE0000247.
RX   PUBMED: 2169353.
RA   Schuele R., Rangarajan P., Kliewer S., Ransone L. J., Bolado J., Yang N., Verma I. M., Evans R. M.
RT   Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor
RL   Cell 62:1217-1226 (1990).
RN   [3]; RE0000271.
RX   PUBMED: 2500251.
RA   Umesono K., Evans R. M.
RT   Determinants of target gene specificity for steroid/thyroid hormone receptors
RL   Cell 57:1139-1146 (1989).
RN   [4]; RE0000998.
RX   PUBMED: 2037566.
RA   Alksnis M., Barkhem T., Stroemstedt P.-E., Ahola H., Kutoh E., Gustafsson J.-A., Poellinger L., Nilsson S.
RT   High level expression of functional full length and truncated glucocorticoid receptor in chinese hamster ovary cells
RL   J. Biol. Chem. 266:10078-10085 (1991).
RN   [5]; RE0001041.
RX   PUBMED: 2071584.
RA   Nazareth L. V., Harbour D. V., Thompson E. B.
RT   Mapping the human glucocorticoid receptor for leukemic cell death
RL   J. Biol. Chem. 266:12976-12980 (1991).
RN   [6]; RE0001752.
RX   PUBMED: 2172797.
RA   Forman B. M., Samuels H. H.
RT   Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model
RL   Mol. Endocrinol. 4:1293-1301 (1990).
RN   [7]; RE0001830.
RX   PUBMED: 3841189.
RA   Weinberger C., Hollenberg S. M., Rosenfeld G. M., Evans R. M.
RT   Domain structure of human glucocorticoid receptor and its relationship to the v-erb-A oncogene product
RL   Nature 318:670-672 (1985).
RN   [8]; RE0001831.
RX   PUBMED: 2867473.
RA   Hollenberg S. M., Weinberger C., Ong E. S., Cerelli G., Oro A., Lebo R., Thompson E. B., Rosenfeld G. M., Evans R. M.
RT   Primary structure and expression of a functional human glucocorticoid receptor cDNA
RL   Nature 318:635-641 (1985).
RN   [9]; RE0002533.
RX   PUBMED: 1924286.
RA   Wright A. P. H., Gustafsson J.-A.
RT   Mechanism of synergistic transcriptional transactivation by the human glucocorticoid receptor
RL   Proc. Natl. Acad. Sci. USA 88:8283-8287 (1991).
RN   [10]; RE0002597.
RX   PUBMED: 2838908.
RA   Akerblom I., Slater E. P., Beato M., Baxter J. D., Mellon P. L.
RT   Negative regulation by glucocorticoids through interference with a cAMP responsive enhancer
RL   Science 241:350-353 (1988).
RN   [11]; RE0002694.
RX   PUBMED: 2115209.
RA   Haerd T., Kelenbach E., Boelens R., Maler B. A., Dahlmann K., Freedman L. P., Carlstedt-Duke J., Yamamoto K. R., Gustafsson J.-A., Kaptein R.
RT   Solution structure of the glucocorticoid receptor DNA-binding domain
RL   Science 249:157-160 (1990).
RN   [12]; RE0002702.
RX   PUBMED: 1376003.
RA   Ku Tai P.-K., Albers M. W., Chang H., Faber L. E., Schreiber S. L.
RT   Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex
RL   Science 256:1315-1318 (1992).
RN   [13]; RE0002813.
RX   PUBMED: 2266108.
RA   Sanchez E. R.
RT   Hsp56: A novel heat shock protein associated with untransformed steroid receptor complexes
RL   J. Biol. Chem. 265:22067-22070 (1990).
RN   [14]; RE0002814.
RX   PUBMED: 1993683.
RA   Dahlman-Wright K., Wright A., Gustafsson J.-A., Carlstedt-Duke J.
RT   Interaction of the glucocorticoid receptor DNA-binding domain with DNA as a dimer is mediated by a short segment of five amino acids
RL   J. Biol. Chem. 266:3107-3112 (1991).
RN   [15]; RE0002818.
RX   PUBMED: 1708098.
RA   Chatterjee V. K. K., Madison L. D., Mayo S., Jameson J. L.
RT   Repression of the human glycoprotein hormone Alpha-subunit gene by glucocorticoids: Evidence for receptor interactions with limiting transcriptional activators
RL   Mol. Endocrinol. 5:100-110 (1991).
RN   [16]; RE0002981.
RX   PUBMED: 1406672.
RA   Kutoh E., Stroemstedt P.-E., Poellinger L.
RT   Functional interference between the ubiquitous and constitutive octamer transcription factor 1 (OTF-1) and the glucocorticoid receptor by direct protein-protein interaction involving the homeo subdomain of OTF-1
RL   Mol. Cell. Biol. 12:4960-4969 (1992).
RN   [17]; RE0003705.
RX   PUBMED: 1279700.
RA   Peattie D. A., Harding M. W., Fleming M. A., DeCenzo M. T., Lippke J. A., Livingston D. J., Benasutti M.
RT   Expression and characterization of the human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor proteins
RL   Proc. Natl. Acad. Sci. USA 89:10974-10978 (1992).
RN   [18]; RE0003707.
RX   PUBMED: 3829127.
RA   Hollenberg S. M., Giguere V., Segul P., Evans R. M.
RT   Colocalization of DNA-binding and transcriptional activation functions in the human glucocorticoid receptor
RL   Cell 49:39-46 (1987).
RN   [19]; RE0003708.
RX   PUBMED: 3742595.
RA   Giguere V., Hollenberg S. M., Rosenfeld M. G., Evans R. M.
RT   Functional domains of the human glucocorticoid receptor
RL   Cell 46:645-652 (1986).
RN   [20]; RE0003709.
RX   PUBMED: 3144438.
RA   Oro A. E., Hollenberg S. M., Evans R. M.
RT   Transcriptional inhibition by a glucocorticoid receptor-beta-galactosidase fusion protein
RL   Cell 55:1109-1114 (1988).
RN   [21]; RE0003710.
RX   PUBMED: 3191531.
RA   Hollenberg S. M., Evans R. M.
RT   Multiple and cooperative trans-activation domains of the human glucocorticoid receptor
RL   Cell 55:899-906 (1988).
RN   [22]; RE0003712.
RX   PUBMED: 2463158.
RA   Straehle U., Schmid W., Schuetz G.
RT   Synergistic action of the glucocorticoid receptor with transcription factors
RL   EMBO J. 7:3389-3395 (1988).
RN   [23]; RE0016449.
RX   PUBMED: 10428842.
RA   Hong H., Yang L., Stallcup M. R.
RT   Hormone-independent transcriptional activation and coactivator binding by novel orphan nuclear receptor ERR3
RL   J. Biol. Chem. 274:22618-22626 (1999).
RN   [24]; RE0023558.
RX   PUBMED: 9343435.
RA   Stoecklin E., Wissler M., Moriggl R., Groner B.
RT   Specific DNA binding of Stat5, but not of glucocorticoid receptor, is required for their functional cooperation in the regulation of gene transcription.
RL   Mol. Cell. Biol. 17:6708-6716 (1997).
RN   [25]; RE0044354.
RX   PUBMED: 11773445.
RA   Christian M., Pohnke Y., Kempf R., Gellersen B., Brosens J. J.
RT   Functional association of PR and CCAAT/enhancer-binding protein beta isoforms: promoter-dependent cooperation between PR-B and liver-enriched inhibitory protein, or liver-enriched activatory protein and PR-A in human endometrial stromal cells
RL   Mol. Endocrinol. 16:141-54 (2002).
RN   [26]; RE0045857.
RX   PUBMED: 12897156.
RA   Kinyamu H. K., Archer T. K.
RT   Estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression
RL   Mol. Cell. Biol. 23:5867-81 (2003).
RN   [27]; RE0047646.
RX   PUBMED: 15289446.
RA   Dschietzig T., Bartsch C., Stangl V., Baumann G., Stangl K.
RT   Identification of the pregnancy hormone relaxin as glucocorticoid receptor agonist.
RL   FASEB J. 18:1536-1538 (2004).
RN   [28]; RE0047761.
RX   PUBMED: 15955845.
RA   Kino T., Tiulpakov A., Ichijo T., Chheng L., Kozasa T., Chrousos G. P.
RT   G protein beta interacts with the glucocorticoid receptor and suppresses its transcriptional activity in the nucleus.
RL   J. Cell Biol. 169:885-896 (2005).
RN   [29]; RE0047789.
RX   PUBMED: 12730237.
RA   Kino T., Souvatzoglou E., De Martino M. U., Tsopanomihalu M., Wan Y., Chrousos G. P.
RT   Protein 14-3-3sigma interacts with and favors cytoplasmic subcellular localization of the glucocorticoid receptor, acting as a negative regulator of the glucocorticoid signaling pathway.
RL   J. Biol. Chem. 278:25651-25656 (2003).
RN   [30]; RE0048506.
RX   PUBMED: 16914745.
RA   Wu Y., Kawate H., Ohnaka K., Nawata H., Takayanagi R.
RT   Nuclear compartmentalization of N-CoR and its interactions with steroid receptors.
RL   Mol. Cell. Biol. 26:6633-6655 (2006).
XX
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