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| | <StructureSection load='4s14' size='340' side='right'caption='[[4s14]], [[Resolution|resolution]] 3.54Å' scene=''> | | <StructureSection load='4s14' size='340' side='right'caption='[[4s14]], [[Resolution|resolution]] 3.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4s14]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4S14 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4S14 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4s14]] is a 2 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=4S14 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4S14 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4D8:(3BETA,4ALPHA,5BETA,14BETA)-3-HYDROXY-4-METHYLCHOLESTA-8,24-DIENE-4-CARBOXYLIC+ACID'>4D8</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.542Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4s15|4s15]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D8:(3BETA,4ALPHA,5BETA,14BETA)-3-HYDROXY-4-METHYLCHOLESTA-8,24-DIENE-4-CARBOXYLIC+ACID'>4D8</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR1F3, RORC, RORG, RZRG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4s14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s14 OCA], [https://pdbe.org/4s14 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4s14 RCSB], [https://www.ebi.ac.uk/pdbsum/4s14 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4s14 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4s14 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4s14 OCA], [http://pdbe.org/4s14 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4s14 RCSB], [http://www.ebi.ac.uk/pdbsum/4s14 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4s14 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN]] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. [[http://www.uniprot.org/uniprot/NRIP1_HUMAN NRIP1_HUMAN]] Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors.<ref>PMID:7641693</ref> <ref>PMID:10364267</ref> <ref>PMID:11509661</ref> <ref>PMID:11518808</ref> <ref>PMID:12554755</ref> <ref>PMID:15060175</ref> | + | [https://www.uniprot.org/uniprot/RORG_HUMAN RORG_HUMAN] Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Huang, P]] | + | [[Category: Huang P]] |
| - | [[Category: Littman, D R]] | + | [[Category: Littman DR]] |
| - | [[Category: Rastinejad, F]] | + | [[Category: Rastinejad F]] |
| - | [[Category: Santori, F R]] | + | [[Category: Santori FR]] |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
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| Structural highlights
Function
RORG_HUMAN Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock.
Publication Abstract from PubMed
Mice deficient in the nuclear hormone receptor RORgammat have defective development of thymocytes, lymphoid organs, Th17 cells, and type 3 innate lymphoid cells. RORgammat binds to oxysterols derived from cholesterol catabolism, but it is not clear whether these are its natural ligands. Here, we show that sterol lipids are necessary and sufficient to drive RORgammat-dependent transcription. We combined overexpression, RNAi, and genetic deletion of metabolic enzymes to study RORgamma-dependent transcription. Our results are consistent with the RORgammat ligand(s) being a cholesterol biosynthetic intermediate (CBI) downstream of lanosterol and upstream of zymosterol. Analysis of lipids bound to RORgamma identified molecules with molecular weights consistent with CBIs. Furthermore, CBIs stabilized the RORgamma ligand-binding domain and induced coactivator recruitment. Genetic deletion of metabolic enzymes upstream of the RORgammat-ligand(s) affected the development of lymph nodes and Th17 cells. Our data suggest that CBIs play a role in lymphocyte development potentially through regulation of RORgammat.
Identification of Natural RORgamma Ligands that Regulate the Development of Lymphoid Cells.,Santori FR, Huang P, van de Pavert SA, Douglass EF Jr, Leaver DJ, Haubrich BA, Keber R, Lorbek G, Konijn T, Rosales BN, Rozman D, Horvat S, Rahier A, Mebius RE, Rastinejad F, Nes WD, Littman DR Cell Metab. 2015 Feb 3;21(2):286-97. doi: 10.1016/j.cmet.2015.01.004. PMID:25651181[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Santori FR, Huang P, van de Pavert SA, Douglass EF Jr, Leaver DJ, Haubrich BA, Keber R, Lorbek G, Konijn T, Rosales BN, Rozman D, Horvat S, Rahier A, Mebius RE, Rastinejad F, Nes WD, Littman DR. Identification of Natural RORgamma Ligands that Regulate the Development of Lymphoid Cells. Cell Metab. 2015 Feb 3;21(2):286-97. doi: 10.1016/j.cmet.2015.01.004. PMID:25651181 doi:http://dx.doi.org/10.1016/j.cmet.2015.01.004
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