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| | <StructureSection load='3p0u' size='340' side='right'caption='[[3p0u]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='3p0u' size='340' side='right'caption='[[3p0u]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3p0u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3P0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P0U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3p0u]] 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=3P0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P0U FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NR2C2, TAK1, TR4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 3Å</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=3p0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p0u OCA], [https://pdbe.org/3p0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p0u RCSB], [https://www.ebi.ac.uk/pdbsum/3p0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p0u 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=3p0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p0u OCA], [https://pdbe.org/3p0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p0u RCSB], [https://www.ebi.ac.uk/pdbsum/3p0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p0u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NR2C2_HUMAN NR2C2_HUMAN]] Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.<ref>PMID:7779113</ref> <ref>PMID:9556573</ref> <ref>PMID:10347174</ref> <ref>PMID:10644740</ref> <ref>PMID:17974920</ref>
| + | [https://www.uniprot.org/uniprot/NR2C2_HUMAN NR2C2_HUMAN] Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.<ref>PMID:7779113</ref> <ref>PMID:9556573</ref> <ref>PMID:10347174</ref> <ref>PMID:10644740</ref> <ref>PMID:17974920</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain which reveals an autorepressed conformation. The ligand-binding pocket of TR4 is filled by the C-terminal half of helix 10 and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding, substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors like TR4.
| + | |
| - | | + | |
| - | The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor.,Zhou XE, Suino-Powell KM, Xu Y, Chan CW, Kruse SW, Reynolds R, Engel JD, Xu HE J Biol Chem. 2010 Nov 9. PMID:21068381<ref>PMID:21068381</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3p0u" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chan, C W]] | + | [[Category: Chan C-W]] |
| - | [[Category: Engel, J D]] | + | [[Category: Engel JD]] |
| - | [[Category: Kruse, S W]] | + | [[Category: Kruse SW]] |
| - | [[Category: Reynolds, R]] | + | [[Category: Reynolds R]] |
| - | [[Category: Suino-Powell, K M]] | + | [[Category: Suino-Powell KM]] |
| - | [[Category: Xu, H E]] | + | [[Category: Xu HE]] |
| - | [[Category: Xu, Y]] | + | [[Category: Xu Y]] |
| - | [[Category: Zhou, X E]] | + | [[Category: Zhou XE]] |
| - | [[Category: Ligand binding domain]]
| + | |
| - | [[Category: Orphan nuclear receptor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Testicular receptor 4]]
| + | |
| Structural highlights
Function
NR2C2_HUMAN Orphan nuclear receptor that can act as a repressor or activator of transcription. An important repressor of nuclear recptor signaling pathways such as retinoic acid receptor, retinoid X, vitamin D3 receptor, thyroid hormone receptor and estrogen receptor pathways. May regulate gene expression during the late phase of spermatogenesis. Together with NR2C1, forms the core of the DRED (direct repeat erythroid-definitive) complex that represses embryonic and fetal globin transcription including that of GATA1. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences. Plays a fundamental role in early embryonic development and embryonic stem cells. Required for normal spermatogenesis and cerebellum development. Appears to be important for neurodevelopmentally regulated behavior (By similarity). Activates transcriptional activity of LHCG. Antagonist of PPARA-mediated transactivation.[1] [2] [3] [4] [5]
References
- ↑ Hirose T, Apfel R, Pfahl M, Jetten AM. The orphan receptor TAK1 acts as a repressor of RAR-, RXR- and T3R-mediated signaling pathways. Biochem Biophys Res Commun. 1995 Jun 6;211(1):83-91. PMID:7779113 doi:http://dx.doi.org/10.1006/bbrc.1995.1781
- ↑ Yan ZH, Karam WG, Staudinger JL, Medvedev A, Ghanayem BI, Jetten AM. Regulation of peroxisome proliferator-activated receptor alpha-induced transactivation by the nuclear orphan receptor TAK1/TR4. J Biol Chem. 1998 May 1;273(18):10948-57. PMID:9556573
- ↑ Lee YF, Young WJ, Lin WJ, Shyr CR, Chang C. Differential regulation of direct repeat 3 vitamin D3 and direct repeat 4 thyroid hormone signaling pathways by the human TR4 orphan receptor. J Biol Chem. 1999 Jun 4;274(23):16198-205. PMID:10347174
- ↑ Zhang Y, Dufau ML. Nuclear orphan receptors regulate transcription of the gene for the human luteinizing hormone receptor. J Biol Chem. 2000 Jan 28;275(4):2763-70. PMID:10644740
- ↑ Tanabe O, Shen Y, Liu Q, Campbell AD, Kuroha T, Yamamoto M, Engel JD. The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription. Genes Dev. 2007 Nov 1;21(21):2832-44. PMID:17974920 doi:10.1101/gad.1593307
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