5dvs - Revision history

OCA at 12:26, 6 March 2024

2024-03-06T12:26:15Z

← Older revision		Revision as of 12:26, 6 March 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>		[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Some estrogen receptor-alpha (ERalpha)-targeted breast cancer therapies such as tamoxifen have tissue-selective or cell-specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell-specific signaling and breast cancer cell proliferation, we synthesized 241 ERalpha ligands based on 19 chemical scaffolds, and compared ligand response using quantitative bioassays for canonical ERalpha activities and X-ray crystallography. Ligands that regulate the dynamics and stability of the coactivator-binding site in the C-terminal ligand-binding domain, called activation function-2 (AF-2), showed similar activity profiles in different cell types. Such ligands induced breast cancer cell proliferation in a manner that was predicted by the canonical recruitment of the coactivators NCOA1/2/3 and induction of the GREB1 proliferative gene. For some ligand series, a single inter-atomic distance in the ligand-binding domain predicted their proliferative effects. In contrast, the N-terminal coactivator-binding site, activation function-1 (AF-1), determined cell-specific signaling induced by ligands that used alternate mechanisms to control cell proliferation. Thus, incorporating systems structural analyses with quantitative chemical biology reveals how ligands can achieve distinct allosteric signaling outcomes through ERalpha.

	Predictive features of ligand-specific signaling through the estrogen receptor.,Nwachukwu JC, Srinivasan S, Zheng Y, Wang S, Min J, Dong C, Liao Z, Nowak J, Wright NJ, Houtman R, Carlson KE, Josan JS, Elemento O, Katzenellenbogen JA, Zhou HB, Nettles KW Mol Syst Biol. 2016 Apr 22;12(4):864. doi: 10.15252/msb.20156701. PMID:27107013<ref>PMID:27107013</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 5dvs" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==

OCA at 22:01, 28 June 2023

2023-06-28T22:01:54Z

← Older revision		Revision as of 22:01, 28 June 2023
Line 3:		Line 3:
	<StructureSection load='5dvs' size='340' side='right'caption='[[5dvs]], [[Resolution\|resolution]] 2.28Å' scene=''>		<StructureSection load='5dvs' size='340' side='right'caption='[[5dvs]], [[Resolution\|resolution]] 2.28Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dvs]] 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=5DVS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5DVS FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dvs]] 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=5DVS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DVS FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=5G7:4~~,4-[(2~~-METHYLPHENYL)CARBONIMIDOYL]DIPHENOL'>5G7</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]] 2.28Å</td></tr>
	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~ESR1~~, ~~ESR, NR3A1~~ (~~[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=5G7:4,4-[(2-METHYLPHENYL)CARBONIMIDOYL]DIPHENOL'>5G7</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=5dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvs OCA], [~~http~~://pdbe.org/5dvs PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5dvs RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5dvs PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5dvs 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=5dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvs OCA], [https://pdbe.org/5dvs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dvs RCSB], [https://www.ebi.ac.uk/pdbsum/5dvs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dvs ProSAT]</span></td></tr>
	</table>		</table>
	~~== Disease ==~~
	[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>		[https://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref>
	<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: Carlson~~, K E~~]]		[[Category: Carlson KE]]
	[[Category: Cavett, V]]		[[Category: Cavett V]]
	[[Category: Dong, C]]		[[Category: Dong C]]
	[[Category: Elemento, O]]		[[Category: Elemento O]]
	[[Category: Houtman, R]]		[[Category: Houtman R]]
	[[Category: Josan~~, J S~~]]		[[Category: Josan JS]]
	[[Category: Katzenellenbogen~~, J A~~]]		[[Category: Katzenellenbogen JA]]
	[[Category: Liao, Z]]		[[Category: Liao Z]]
	[[Category: Min, J]]		[[Category: Min J]]
	[[Category: Nettles~~, K W~~]]		[[Category: Nettles KW]]
	[[Category: Nowak, J]]		[[Category: Nowak J]]
	[[Category: Nwachukwu~~, J C~~]]		[[Category: Nwachukwu JC]]
	[[Category: Srinivasan, S]]		[[Category: Srinivasan S]]
	[[Category: Wang, S]]		[[Category: Wang S]]
	[[Category: Wright~~, N J~~]]		[[Category: Wright NJ]]
	[[Category: Zheng, Y]]		[[Category: Zheng Y]]
	[[Category: Zhou~~, H B]]~~		[[Category: Zhou HB]]
	~~[[Category: Ligand binding]]~~
	~~[[Category: Nuclear receptor]]~~
	~~[[Category: Protein-ligand complex]]~~
	~~[[Category: Transcription]]~~
	~~[[Category: Transcription factor~~]]

OCA at 08:09, 15 April 2020

2020-04-15T08:09:21Z

← Older revision		Revision as of 08:09, 15 April 2020
Line 1:		Line 1:

	==Crystal Structure of the ER-alpha Ligand-binding Domain in Complex with a 2-Methyl-substituted Triaryl-imine 4,4'-[(2-methylphenyl)carbonimidoyl]diphenol==		==Crystal Structure of the ER-alpha Ligand-binding Domain in Complex with a 2-Methyl-substituted Triaryl-imine 4,4'-[(2-methylphenyl)carbonimidoyl]diphenol==
	<StructureSection load='5dvs' size='340' side='right' caption='[[5dvs]], [[Resolution\|resolution]] 2.28Å' scene=''>		<StructureSection load='5dvs' size='340' side='right'caption='[[5dvs]], [[Resolution\|resolution]] 2.28Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dvs]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DVS OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5DVS FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dvs]] 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=5DVS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DVS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5G7:4,4-[(2-METHYLPHENYL)CARBONIMIDOYL]DIPHENOL'>5G7</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5G7:4,4-[(2-METHYLPHENYL)CARBONIMIDOYL]DIPHENOL'>5G7</scene></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=5dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvs OCA], [http://pdbe.org/5dvs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dvs RCSB], [http://www.ebi.ac.uk/pdbsum/5dvs PDBsum]</span></td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ESR1, ESR, NR3A1 ([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://proteopedia.org/fgij/fg.htm?mol=5dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvs OCA], [http://pdbe.org/5dvs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dvs RCSB], [http://www.ebi.ac.uk/pdbsum/5dvs PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dvs ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5dvs" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5dvs" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Estrogen receptor 3D structures\|Estrogen receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Carlson, K E]]		[[Category: Carlson, K E]]
	[[Category: Cavett, V]]		[[Category: Cavett, V]]

OCA at 03:36, 11 May 2016

2016-05-11T03:36:12Z

← Older revision		Revision as of 03:36, 11 May 2016
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	The ~~entry 5dvs~~ is ~~ON HOLD~~ ~~until Paper~~ Publication		==Crystal Structure of the ER-alpha Ligand-binding Domain in Complex with a 2-Methyl-substituted Triaryl-imine 4,4'-[(2-methylphenyl)carbonimidoyl]diphenol==
			<StructureSection load='5dvs' size='340' side='right' caption='[[5dvs]], [[Resolution\|resolution]] 2.28Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5dvs]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DVS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DVS FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5G7:4,4-[(2-METHYLPHENYL)CARBONIMIDOYL]DIPHENOL'>5G7</scene></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=5dvs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dvs OCA], [http://pdbe.org/5dvs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dvs RCSB], [http://www.ebi.ac.uk/pdbsum/5dvs PDBsum]</span></td></tr>
			</table>
			== Disease ==
			[[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Note=Chromosomal aberrations involving NCOA2 may be a cause of acute myeloid leukemias. Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation.
			== Function ==
			[[http://www.uniprot.org/uniprot/ESR1_HUMAN ESR1_HUMAN]] Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Isoform 3 can bind to ERE and inhibit isoform 1.<ref>PMID:7651415</ref> <ref>PMID:10970861</ref> <ref>PMID:9328340</ref> <ref>PMID:10681512</ref> <ref>PMID:10816575</ref> <ref>PMID:11477071</ref> <ref>PMID:11682626</ref> <ref>PMID:15078875</ref> <ref>PMID:16043358</ref> <ref>PMID:15891768</ref> <ref>PMID:16684779</ref> <ref>PMID:18247370</ref> <ref>PMID:17932106</ref> <ref>PMID:19350539</ref> <ref>PMID:20705611</ref> <ref>PMID:21937726</ref> <ref>PMID:21330404</ref> <ref>PMID:22083956</ref> [[http://www.uniprot.org/uniprot/NCOA2_HUMAN NCOA2_HUMAN]] Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues.<ref>PMID:9430642</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Some estrogen receptor-alpha (ERalpha)-targeted breast cancer therapies such as tamoxifen have tissue-selective or cell-specific activities, while others have similar activities in different cell types. To identify biophysical determinants of cell-specific signaling and breast cancer cell proliferation, we synthesized 241 ERalpha ligands based on 19 chemical scaffolds, and compared ligand response using quantitative bioassays for canonical ERalpha activities and X-ray crystallography. Ligands that regulate the dynamics and stability of the coactivator-binding site in the C-terminal ligand-binding domain, called activation function-2 (AF-2), showed similar activity profiles in different cell types. Such ligands induced breast cancer cell proliferation in a manner that was predicted by the canonical recruitment of the coactivators NCOA1/2/3 and induction of the GREB1 proliferative gene. For some ligand series, a single inter-atomic distance in the ligand-binding domain predicted their proliferative effects. In contrast, the N-terminal coactivator-binding site, activation function-1 (AF-1), determined cell-specific signaling induced by ligands that used alternate mechanisms to control cell proliferation. Thus, incorporating systems structural analyses with quantitative chemical biology reveals how ligands can achieve distinct allosteric signaling outcomes through ERalpha.

	~~Authors: Nwachukwu, J.C~~., ~~Wright, N.J.~~, Srinivasan, S., Zheng, Y., Wang, S., Min, J., Dong, C., Liao, Z~~., Cavett, V.~~, Nowak, J., Houtman, R., Carlson~~, K.E.~~, Josan~~, J.S.~~, Elemento, O., Katzenellenbogen~~, J.A.~~, Zhou, H.B.~~, Nettles, K~~.W.		Predictive features of ligand-specific signaling through the estrogen receptor.,Nwachukwu JC, Srinivasan S, Zheng Y, Wang S, Min J, Dong C, Liao Z, Nowak J, Wright NJ, Houtman R, Carlson KE, Josan JS, Elemento O, Katzenellenbogen JA, Zhou HB, Nettles KW Mol Syst Biol. 2016 Apr 22;12(4):864. doi: 10.15252/msb.20156701. PMID:27107013<ref>PMID:27107013</ref>

	~~Description~~:		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	[[Category: ~~Unreleased Structures~~]]		</div>
			<div class="pdbe-citations 5dvs" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Carlson, K E]]
			[[Category: Cavett, V]]
			[[Category: Dong, C]]
			[[Category: Elemento, O]]
	[[Category: Houtman, R]]		[[Category: Houtman, R]]
	[[Category: ~~Zheng, Y]]~~		[[Category: Josan, J S]]
	~~[[Category: Nwachukwu~~, J~~.C]]~~		[[Category: Katzenellenbogen, J A]]
	~~[[Category: Dong, C~~]]
	[[Category: ~~Cavett~~, ~~V]]~~
	~~[[Category: Wright, N.~~J]]
	~~[[Category: Wang, S~~]]
	[[Category: Liao, Z]]		[[Category: Liao, Z]]
	[[Category: ~~Katzenellenbogen~~, J.A]]		[[Category: Min, J]]
			[[Category: Nettles, K W]]
			[[Category: Nowak, J]]
			[[Category: Nwachukwu, J C]]
	[[Category: Srinivasan, S]]		[[Category: Srinivasan, S]]
	[[Category: ~~Nowak~~, J]]		[[Category: Wang, S]]
	[[Category: ~~Min~~, J]]		[[Category: Wright, N J]]
	[[Category: ~~Josan~~, ~~J.S~~]]		[[Category: Zheng, Y]]
	[[Category: ~~Nettles~~, ~~K.W~~]]		[[Category: Zhou, H B]]
	[[Category: ~~Carlson, K.E~~]]		[[Category: Ligand binding]]
	[[Category: ~~Zhou, H.B~~]]		[[Category: Nuclear receptor]]
	[[Category: ~~Elemento, O~~]]		[[Category: Protein-ligand complex]]
			[[Category: Transcription]]
			[[Category: Transcription factor]]

OCA at 11:27, 16 December 2015

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	[[Category: Nwachukwu, J.C]]		[[Category: Nwachukwu, J.C]]
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	[[Category: Nettles, K.W]]		[[Category: Nettles, K.W]]
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	[[Category: Zhou, H.B]]		[[Category: Zhou, H.B]]
	[[Category: Elemento, O]]		[[Category: Elemento, O]]

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	Authors: Nwachukwu, J.C., Wright, N.J., Srinivasan, S., Zheng, Y., Wang, S., Min, J., Dong, C., Liao, Z., Cavett, V., Nowak, J., Houtman, R., Carlson, K.E., Josan, J.S., Elemento, O., Katzenellenbogen, J.A., Zhou, H.B., Nettles, K.W.		Authors: Nwachukwu, J.C., Wright, N.J., Srinivasan, S., Zheng, Y., Wang, S., Min, J., Dong, C., Liao, Z., Cavett, V., Nowak, J., Houtman, R., Carlson, K.E., Josan, J.S., Elemento, O., Katzenellenbogen, J.A., Zhou, H.B., Nettles, K.W.

OCA: Protected "5dvs" [edit=sysop:move=sysop]

2015-09-30T13:35:56Z

Protected "5dvs" [edit=sysop:move=sysop]

← Older revision	Revision as of 13:35, 30 September 2015
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OCA: New page: '''Unreleased structure''' The entry 5dvs is ON HOLD Authors: Nwachukwu, J.C., Wright, N.J., Srinivasan, S., Zheng, Y., Wang, S., Min, J., Dong, C., Liao, Z., Cavett, V., Nowak, J., Hou...

2015-09-30T13:35:54Z

New page: '''Unreleased structure''' The entry 5dvs is ON HOLD Authors: Nwachukwu, J.C., Wright, N.J., Srinivasan, S., Zheng, Y., Wang, S., Min, J., Dong, C., Liao, Z., Cavett, V., Nowak, J., Hou...

New page

'''Unreleased structure'''

The entry 5dvs is ON HOLD

Authors: Nwachukwu, J.C., Wright, N.J., Srinivasan, S., Zheng, Y., Wang, S., Min, J., Dong, C., Liao, Z., Cavett, V., Nowak, J., Houtman, R., Carlson, K.E., Josan, J.S., Elemento, O., Katzenellenbogen, J.A., Zhou, H.B., Nettles, K.W.

Description:
[[Category: Unreleased Structures]]
[[Category: Zheng, Y]]
[[Category: Nwachukwu, J.C]]
[[Category: Liao, Z]]
[[Category: Katzenellenbogen, J.A]]
[[Category: Srinivasan, S]]
[[Category: Min, J]]
[[Category: Carlson, K.E]]
[[Category: Houtman, R]]
[[Category: Dong, C]]
[[Category: Cavett, V]]
[[Category: Wright, N.J]]
[[Category: Wang, S]]
[[Category: Nowak, J]]
[[Category: Josan, J.S]]
[[Category: Nettles, K.W]]
[[Category: Zhou, H.B]]
[[Category: Elemento, O]]