1yuc

<StructureSection load='1yuc' size='340' side='right' caption='[[1yuc]], [[Resolution|resolution]] 1.90&Aring;' scene=''>

<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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1YUC FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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='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='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=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>

== Disease ==

[[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>

[[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>

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== Publication Abstract from PubMed ==

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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== References ==

[[Category: Human]]

[[Category: Choi, Y]]

[[Category: Guan, Z]]

[[Category: Hager, J M]]

[[Category: McDonnell, D P]]

[[Category: Moore, D D]]

[[Category: Ortlund, E A]]

[[Category: Raetz, C R.H]]

[[Category: Redinbo, M R]]

[[Category: Safi, R]]

[[Category: Solomon, I H]]

[[Category: Tripathy, A]]

[[Category: Yoonkwang, L]]

[[Category: Transcription regulation]]