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| <StructureSection load='1yuc' size='340' side='right'caption='[[1yuc]], [[Resolution|resolution]] 1.90Å' scene=''> | | <StructureSection load='1yuc' size='340' side='right'caption='[[1yuc]], [[Resolution|resolution]] 1.90Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[1yuc]] is a 4 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=1YUC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1YUC FirstGlance]. <br> | | <table><tr><td colspan='2'>[[1yuc]] 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=1YUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YUC FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.9Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR5A2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPH:L-ALPHA-PHOSPHATIDYL-BETA-OLEOYL-GAMMA-PALMITOYL-PHOSPHATIDYLETHANOLAMINE'>EPH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1yuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yuc OCA], [http://pdbe.org/1yuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1yuc RCSB], [http://www.ebi.ac.uk/pdbsum/1yuc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1yuc ProSAT]</span></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=1yuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yuc OCA], [https://pdbe.org/1yuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yuc RCSB], [https://www.ebi.ac.uk/pdbsum/1yuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yuc ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
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| [[http://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN]] Defects in NR0B2 may be associated with obesity (OBESITY) [MIM:[http://omim.org/entry/601665 601665]]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:11136233</ref>
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| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN]] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. [[http://www.uniprot.org/uniprot/NR0B2_HUMAN NR0B2_HUMAN]] Acts as a transcriptional regulator. Acts as a negative regulator of receptor-dependent signaling pathways. Specifically inhibits transactivation of the nuclear receptor with whom it interacts. Inhibits transcriptional activity of NEUROD1 on E-box-containing promoter by interfering with the coactivation function of the p300/CBP-mediated trancription complex for NEUROD1.<ref>PMID:14752053</ref> | | [https://www.uniprot.org/uniprot/NR5A2_HUMAN NR5A2_HUMAN] Binds to the sequence element 5'-AACGACCGACCTTGAG-3' of the enhancer II of hepatitis B virus genes, a critical cis-element of their expression and regulation. May be responsible for the liver-specific activity of enhancer II, probably in combination with other hepatocyte transcription factors. Key regulator of cholesterol 7-alpha-hydroxylase gene (CYP7A) expression in liver. May also contribute to the regulation of pancreas-specific genes and play important roles in embryonic development. |
| == Evolutionary Conservation == | | == Evolutionary Conservation == |
| [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yuc ConSurf]. | | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1yuc ConSurf]. |
| <div style="clear:both"></div> | | <div style="clear:both"></div> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| The human nuclear receptor liver receptor homolog 1 (hLRH-1) plays an important role in the development of breast carcinomas. This orphan receptor is efficiently downregulated by the unusual co-repressor SHP and has been thought to be ligand-independent. We present the crystal structure at a resolution of 1.9 A of the ligand-binding domain of hLRH-1 in complex with the NR box 1 motif of human SHP, which we find contacts the AF-2 region of hLRH-1 using selective structural motifs. Electron density indicates phospholipid bound within the ligand-binding pocket, which we confirm using mass spectrometry of solvent-extracted samples. We further show that pocket mutations reduce phospholipid binding and receptor activity in vivo. Our results indicate that hLRH-1's control of gene expression is mediated by phospholipid binding, and establish hLRH-1 as a novel target for compounds designed to slow breast cancer development.
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| Modulation of human nuclear receptor LRH-1 activity by phospholipids and SHP.,Ortlund EA, Lee Y, Solomon IH, Hager JM, Safi R, Choi Y, Guan Z, Tripathy A, Raetz CR, McDonnell DP, Moore DD, Redinbo MR Nat Struct Mol Biol. 2005 Apr;12(4):357-63. Epub 2005 Feb 22. PMID:15723037<ref>PMID:15723037</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 1yuc" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Liver receptor homolog-1|Liver receptor homolog-1]] | | *[[Liver receptor homolog-1|Liver receptor homolog-1]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]] | | [[Category: Homo sapiens]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Choi, Y]] | | [[Category: Choi Y]] |
| [[Category: Guan, Z]] | | [[Category: Guan Z]] |
| [[Category: Hager, J M]] | | [[Category: Hager JM]] |
| [[Category: McDonnell, D P]] | | [[Category: McDonnell DP]] |
| [[Category: Moore, D D]] | | [[Category: Moore DD]] |
| [[Category: Ortlund, E A]] | | [[Category: Ortlund EA]] |
| [[Category: Raetz, C R.H]] | | [[Category: Raetz CRH]] |
| [[Category: Redinbo, M R]] | | [[Category: Redinbo MR]] |
| [[Category: Safi, R]] | | [[Category: Safi R]] |
| [[Category: Solomon, I H]] | | [[Category: Solomon IH]] |
| [[Category: Tripathy, A]] | | [[Category: Tripathy A]] |
| [[Category: Yoonkwang, L]] | | [[Category: Yoonkwang L]] |
| [[Category: Liver receptor homologue 1]]
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| [[Category: Lrh-1]]
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| [[Category: Nuclear receptor ligand binding domain]]
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| [[Category: Phospholipid]]
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| [[Category: Shp]]
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| [[Category: Small heterodimer partner]]
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| [[Category: Transcription regulation]]
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