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| - | {{Seed}} | |
| - | [[Image:3e7c.png|left|200px]] | |
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| - | <!-- | + | ==Glucocorticoid Receptor LBD bound to GSK866== |
| - | The line below this paragraph, containing "STRUCTURE_3e7c", creates the "Structure Box" on the page.
| + | <StructureSection load='3e7c' size='340' side='right'caption='[[3e7c]], [[Resolution|resolution]] 2.15Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3e7c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7C FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=866:5-AMINO-N-[(2S)-2-({[(2,6-DICHLOROPHENYL)CARBONYL](ETHYL)AMINO}METHYL)-3,3,3-TRIFLUORO-2-HYDROXYPROPYL]-1-(4-FLUOROPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE'>866</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | {{STRUCTURE_3e7c| PDB=3e7c | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3e7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7c OCA], [https://pdbe.org/3e7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7c RCSB], [https://www.ebi.ac.uk/pdbsum/3e7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7c ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:[https://omim.org/entry/138040 138040]; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.<ref>PMID:12050230</ref> <ref>PMID:1704018</ref> <ref>PMID:7683692</ref> <ref>PMID:11589680</ref> <ref>PMID:11701741</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GCR_HUMAN GCR_HUMAN] Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.<ref>PMID:21664385</ref> |
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| - | ===Glucocorticoid Receptor LBD bound to GSK866=== | + | ==See Also== |
| - | | + | *[[Glucocorticoid receptor 3D structures|Glucocorticoid receptor 3D structures]] |
| - | | + | == References == |
| - | <!--
| + | <references/> |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_18952422}}, adds the Publication Abstract to the page
| + | __TOC__ |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 18952422 is the PubMed ID number.
| + | </StructureSection> |
| - | -->
| + | |
| - | {{ABSTRACT_PUBMED_18952422}}
| + | |
| - | | + | |
| - | ==About this Structure==
| + | |
| - | 3E7C is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7C OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:18952422</ref><references group="xtra"/> | + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Bledsoe, R K.]] | + | [[Category: Large Structures]] |
| - | [[Category: Madauss, K P.]] | + | [[Category: Bledsoe RK]] |
| - | [[Category: Mclay, I.]] | + | [[Category: Madauss KP]] |
| - | [[Category: Stewart, E L.]] | + | [[Category: Mclay I]] |
| - | [[Category: Williams, S P.]] | + | [[Category: Stewart EL]] |
| - | [[Category: Activator]] | + | [[Category: Williams SP]] |
| - | [[Category: Alternative initiation]]
| + | |
| - | [[Category: Alternative splicing]]
| + | |
| - | [[Category: Chromatin regulator]]
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| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Dna-binding]]
| + | |
| - | [[Category: Glucocorticoid receptor]]
| + | |
| - | [[Category: Gr]]
| + | |
| - | [[Category: Lipid-binding]]
| + | |
| - | [[Category: Metal-binding]]
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| - | [[Category: Nuclear receptor]]
| + | |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
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| - | [[Category: Pseudohermaphroditism]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Steroid-binding]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Ubl conjugation]]
| + | |
| - | [[Category: Zinc]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 10 15:16:37 2009''
| + | |
| Structural highlights
Disease
GCR_HUMAN Defects in NR3C1 are a cause of glucocorticoid resistance (GCRES) [MIM:138040; also known as cortisol resistance. It is a hypertensive, hyperandrogenic disorder characterized by increased serum cortisol concentrations. Inheritance is autosomal dominant.[1] [2] [3] [4] [5]
Function
GCR_HUMAN Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. Plays a significant role in transactivation.[6]
See Also
References
- ↑ Vottero A, Kino T, Combe H, Lecomte P, Chrousos GP. A novel, C-terminal dominant negative mutation of the GR causes familial glucocorticoid resistance through abnormal interactions with p160 steroid receptor coactivators. J Clin Endocrinol Metab. 2002 Jun;87(6):2658-67. PMID:12050230
- ↑ Hurley DM, Accili D, Stratakis CA, Karl M, Vamvakopoulos N, Rorer E, Constantine K, Taylor SI, Chrousos GP. Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest. 1991 Feb;87(2):680-6. PMID:1704018 doi:http://dx.doi.org/10.1172/JCI115046
- ↑ Malchoff DM, Brufsky A, Reardon G, McDermott P, Javier EC, Bergh CH, Rowe D, Malchoff CD. A mutation of the glucocorticoid receptor in primary cortisol resistance. J Clin Invest. 1993 May;91(5):1918-25. PMID:7683692 doi:http://dx.doi.org/10.1172/JCI116410
- ↑ Ruiz M, Lind U, Gafvels M, Eggertsen G, Carlstedt-Duke J, Nilsson L, Holtmann M, Stierna P, Wikstrom AC, Werner S. Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance. Clin Endocrinol (Oxf). 2001 Sep;55(3):363-71. PMID:11589680
- ↑ Kino T, Stauber RH, Resau JH, Pavlakis GN, Chrousos GP. Pathologic human GR mutant has a transdominant negative effect on the wild-type GR by inhibiting its translocation into the nucleus: importance of the ligand-binding domain for intracellular GR trafficking. J Clin Endocrinol Metab. 2001 Nov;86(11):5600-8. PMID:11701741
- ↑ Psarra AM, Sekeris CE. Glucocorticoids induce mitochondrial gene transcription in HepG2 cells: role of the mitochondrial glucocorticoid receptor. Biochim Biophys Acta. 2011 Oct;1813(10):1814-21. doi:, 10.1016/j.bbamcr.2011.05.014. Epub 2011 Jun 2. PMID:21664385 doi:10.1016/j.bbamcr.2011.05.014
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