3kmr - Revision history

OCA at 08:19, 6 September 2023

OCA — Wed, 06 Sep 2023 08:19:21 GMT

←Older revision		Revision as of 08:19, 6 September 2023
Line 1:		Line 1:

	==Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment==		==Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment==
-	<StructureSection load='3kmr' size='340' side='right' caption='[[3kmr]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='3kmr' size='340' side='right'caption='[[3kmr]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3kmr]] 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=3KMR OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3KMR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3kmr]] 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=3KMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KMR FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=EQN:4~~-{[~~(5,5,~~8~~,8-TETRAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CARBONYL]AMINO}BENZOIC+ACID'>EQN</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]] 1.8Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat"~~>NR1B1, RARA ([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=EQN:4-{[(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CARBONYL]AMINO}BENZOIC+ACID'>EQN</scene></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks'>~~[~~http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase]~~, ~~with EC number [http://www.brenda~~-~~enzymes.info/php/result_flat.php4?ecno=~~2~~.3.1.48 2.3.1.48~~] </~~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=3kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmr OCA], [https://pdbe.org/3kmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3kmr RCSB], [https://www.ebi.ac.uk/pdbsum/3kmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3kmr 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=3kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmr OCA], [~~http~~://pdbe.org/3kmr PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3kmr RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3kmr PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3kmr ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation. [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.	+	[https://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN] Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation.
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis.<ref>PMID:16417524</ref> <ref>PMID:19850744</ref> <ref>PMID:19377461</ref> <ref>PMID:20215566</ref> [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref>	+	[https://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis.<ref>PMID:16417524</ref> <ref>PMID:19850744</ref> <ref>PMID:19377461</ref> <ref>PMID:20215566</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 34:		Line 33:

	==See Also==		==See Also==
-	*[[Retinoic acid receptor\|Retinoic acid receptor]]	+	*[[Retinoic acid receptor 3D structures\|Retinoic acid receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Histone acetyltransferase~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
-	[[Category: Bourguet, W]]	+	[[Category: Bourguet W]]
-	[[Category: Teyssier, C]]	+	[[Category: Teyssier C]]
-	~~[[Category: Activator]]~~	+
-	~~[[Category: Acyltransferase]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Isopeptide bond]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Nuclear receptor transcription factor ligand binding domain]]~~	+
-	~~[[Category: Nucleus]]~~	+
-	~~[[Category: Phosphoprotein]]~~	+
-	~~[[Category: Proto-oncogene]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription regulation]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Zinc-finger~~]]	+

OCA at 09:14, 26 December 2018

OCA — Wed, 26 Dec 2018 09:14:24 GMT

←Older revision		Revision as of 09:14, 26 December 2018
Line 17:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3kmr_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3kmr_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 18:19, 4 August 2016

OCA — Thu, 04 Aug 2016 18:19:28 GMT

←Older revision		Revision as of 18:19, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment==		==Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment==
	<StructureSection load='3kmr' size='340' side='right' caption='[[3kmr]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='3kmr' size='340' side='right' caption='[[3kmr]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3kmr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KMR FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3kmr]] 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=3KMR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KMR FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EQN:4-{[(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CARBONYL]AMINO}BENZOIC+ACID'>EQN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EQN:4-{[(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CARBONYL]AMINO}BENZOIC+ACID'>EQN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1B1, RARA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1B1, RARA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=3kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kmr RCSB], [http://www.ebi.ac.uk/pdbsum/3kmr PDBsum]</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=3kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmr OCA], [http://pdbe.org/3kmr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3kmr RCSB], [http://www.ebi.ac.uk/pdbsum/3kmr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3kmr ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ 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=3kmr ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 31:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3kmr" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Bourguet, W]]		[[Category: Bourguet, W]]
	[[Category: Teyssier, C]]		[[Category: Teyssier, C]]

OCA at 16:04, 18 December 2014

OCA — Thu, 18 Dec 2014 16:04:05 GMT

←Older revision		Revision as of 16:04, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3kmr\| PDB=3kmr \| SCENE= }}~~	+	==Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment==
-	===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===	+	<StructureSection load='3kmr' size='340' side='right' caption='[[3kmr]], [[Resolution\|resolution]] 1.80Å' scene=''>
-	{~~{ABSTRACT_PUBMED_20543827}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3kmr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KMR FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EQN:4-{[(5,5,8,8-TETRAMETHYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CARBONYL]AMINO}BENZOIC+ACID'>EQN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NR1B1, RARA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] </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=3kmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3kmr OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3kmr RCSB], [http://www.ebi.ac.uk/pdbsum/3kmr PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
	[[http://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation. [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.		[[http://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation. [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis.<ref>PMID:16417524</ref> <ref>PMID:19850744</ref> <ref>PMID:19377461</ref> <ref>PMID:20215566</ref> [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref> <ref>PMID:7481822</ref> <ref>PMID:9223431</ref> <ref>PMID:9296499</ref> <ref>PMID:9223281</ref> <ref>PMID:10449719</ref> <ref>PMID:12954634</ref>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/km/3kmr_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</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/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	In the absence of ligand, some nuclear receptors, including retinoic acid receptor (RAR), act as transcriptional repressors by recruiting corepressor complexes to target genes. This constitutive repression is crucial in metazoan reproduction, development and homeostasis. However, its specific molecular determinants had remained obscure. Using structural, biochemical and cell-based assays, we show that the basal repressive activity of RAR is conferred by an extended beta-strand that forms an antiparallel beta-sheet with specific corepressor residues. Agonist binding induces a beta-strand-to-alpha-helix transition that allows for helix H11 formation, which in turn provokes corepressor release, repositioning of helix H12 and coactivator recruitment. Several lines of evidence suggest that this structural switch could be implicated in the intrinsic repressor function of other nuclear receptors. Finally, we report on the molecular mechanism by which inverse agonists strengthen corepressor interaction and enhance gene silencing by RAR.

-	~~==Function==~~	+	A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor.,le Maire A, Teyssier C, Erb C, Grimaldi M, Alvarez S, de Lera AR, Balaguer P, Gronemeyer H, Royer CA, Germain P, Bourguet W Nat Struct Mol Biol. 2010 Jul;17(7):801-7. Epub 2010 Jun 13. PMID:20543827<ref>PMID:20543827</ref>
-	~~[[http://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all~~-~~trans or 9-cis retinoic acid, and regulate~~ gene ~~expression in various biological processes. The RXR/RAR heterodimers bind to the~~ retinoic acid ~~response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5~~. ~~In the absence of ligand~~, ~~the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation~~, ~~chromatin condensation and transcriptional suppression. On ligand binding~~, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, ~~may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG~~, ~~required for skeletal growth~~, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis.<ref>PMID:16417524</ref><ref>PMID:19850744</ref><ref>PMID:19377461</ref><ref>PMID:20215566</ref> [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, ~~such as for steroids (PGR~~, ~~GR and ER)~~, ~~retinoids (RXRs)~~, ~~thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3~~, ~~STAT5A, STAT5B and STAT6 transcription factors~~. ~~Displays histone acetyltransferase activity toward H3 and H4~~; ~~the relevance of such activity remains however unclear~~. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:~~9427757</ref><ref>PMID:7481822</ref><ref>PMID:9223431</ref><ref>PMID:9296499</ref><ref>PMID:9223281</ref><ref>PMID:10449719</ref>~~<ref>PMID:~~12954634~~</ref>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[3kmr]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Retinoic acid receptor\|Retinoic acid receptor]]		*[[Retinoic acid receptor\|Retinoic acid receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:020543827</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Bourguet, W.]]	+	[[Category: Bourguet, W]]
-	[[Category: Teyssier, C.]]	+	[[Category: Teyssier, C]]
	[[Category: Activator]]		[[Category: Activator]]
	[[Category: Acyltransferase]]		[[Category: Acyltransferase]]

OCA at 00:13, 25 March 2013

OCA — Mon, 25 Mar 2013 00:13:21 GMT

←Older revision		Revision as of 00:13, 25 March 2013
Line 1:		Line 1:
-	[[Image:3kmr.png\|left\|200px]]
-
	{{STRUCTURE_3kmr\| PDB=3kmr \| SCENE= }}		{{STRUCTURE_3kmr\| PDB=3kmr \| SCENE= }}
-
	===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===		===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===
		+	{{ABSTRACT_PUBMED_20543827}}

-	~~{{ABSTRACT_PUBMED_20543827}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Note=Chromosomal aberrations involving RARA are commonly found in acute promyelocytic leukemia. Translocation t(11;17)(q32;q21) with ZBTB16/PLZF; translocation t(15;17)(q21;q21) with PML; translocation t(5;17)(q32;q11) with NPM. The PML-RARA oncoprotein requires both the PML ring structure and coiled-coil domain for both interaction with UBE2I, nuclear microspeckle location and sumoylation. In addition, the coiled-coil domain functions in blocking RA-mediated transactivation and cell differentiation. [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Note=A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/RARA_HUMAN RARA_HUMAN]] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. RARA plays an essential role in the regulation of retinoic acid-induced germ cell development during spermatogenesis. Has a role in the survival of early spermatocytes at the beginning prophase of meiosis. In Sertoli cells, may promote the survival and development of early meiotic prophase spermatocytes. In concert with RARG, required for skeletal growth, matrix homeostasis and growth plate function (By similarity). Regulates expression of target genes in a ligand-dependent manner by recruiting chromatin complexes containing MLL5. Mediates retinoic acid-induced granulopoiesis.<ref>PMID:16417524</ref><ref>PMID:19850744</ref><ref>PMID:19377461</ref><ref>PMID:20215566</ref> [[http://www.uniprot.org/uniprot/NCOA1_HUMAN NCOA1_HUMAN]] Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.<ref>PMID:9427757</ref><ref>PMID:7481822</ref><ref>PMID:9223431</ref><ref>PMID:9296499</ref><ref>PMID:9223281</ref><ref>PMID:10449719</ref><ref>PMID:12954634</ref>

	==About this Structure==		==About this Structure==
Line 14:		Line 16:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:020543827</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020543827</ref><references group="xtra"/><references/>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA: Protected "3kmr" [edit=sysop:move=sysop]

OCA — Sat, 20 Oct 2012 16:21:44 GMT

Protected "3kmr" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:21, 20 October 2012

OCA at 16:21, 20 October 2012

OCA — Sat, 20 Oct 2012 16:21:41 GMT

←Older revision		Revision as of 16:21, 20 October 2012
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-	{{Seed}}
	[[Image:3kmr.png\|left\|200px]]		[[Image:3kmr.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3kmr", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3kmr\| PDB=3kmr \| SCENE= }}		{{STRUCTURE_3kmr\| PDB=3kmr \| SCENE= }}

	===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===		===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20543827}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20543827 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20543827}}		{{ABSTRACT_PUBMED_20543827}}

	==About this Structure==		==About this Structure==
-	~~3KMR~~ is a 2 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA].	+	[[3kmr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA].
		+
		+	==See Also==
		+	*[[Retinoic acid receptor\|Retinoic acid receptor]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20543827~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020543827</ref><references group="xtra"/>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
Line 42:		Line 33:
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 14 15:52:31 2010''

OCA at 11:46, 14 July 2010

OCA — Wed, 14 Jul 2010 11:46:22 GMT

←Older revision		Revision as of 11:46, 14 July 2010
Line 30:		Line 30:
	[[Category: Activator]]		[[Category: Activator]]
	[[Category: Acyltransferase]]		[[Category: Acyltransferase]]
-	[[Category: Alternative splicing]]
-	[[Category: Chromosomal rearrangement]]
	[[Category: Dna-binding]]		[[Category: Dna-binding]]
	[[Category: Isopeptide bond]]		[[Category: Isopeptide bond]]
Line 38:		Line 36:
	[[Category: Nucleus]]		[[Category: Nucleus]]
	[[Category: Phosphoprotein]]		[[Category: Phosphoprotein]]
-	[[Category: Polymorphism]]
	[[Category: Proto-oncogene]]		[[Category: Proto-oncogene]]
	[[Category: Receptor]]		[[Category: Receptor]]
Line 44:		Line 41:
	[[Category: Transcription regulation]]		[[Category: Transcription regulation]]
	[[Category: Transferase]]		[[Category: Transferase]]
-	[[Category: Ubl conjugation]]
-	[[Category: Zinc]]
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Jun 23 08~~:32:08 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 14 15:52:31 2010''

OCA at 04:26, 23 June 2010

OCA — Wed, 23 Jun 2010 04:26:50 GMT

←Older revision		Revision as of 04:26, 23 June 2010
Line 1:		Line 1:
	{{Seed}}		{{Seed}}
-	[[Image:3kmr.~~jpg~~\|left\|200px]]	+	[[Image:3kmr.png\|left\|200px]]

	<!--		<!--
Line 12:		Line 12:
	===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===		===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20543827}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20543827 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20543827}}

	==About this Structure==		==About this Structure==
	3KMR is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA].		3KMR is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20543827</ref><references group="xtra"/>
	[[Category: Histone acetyltransferase]]		[[Category: Histone acetyltransferase]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
Line 39:		Line 48:
	[[Category: Zinc-finger]]		[[Category: Zinc-finger]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 2 08:38:27 2010''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 23 08:32:08 2010''

OCA at 04:34, 2 June 2010

OCA — Wed, 02 Jun 2010 04:34:02 GMT

←Older revision		Revision as of 04:34, 2 June 2010
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3kmr.jpg\|left\|200px]]

-	The ~~entry 3kmr~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3kmr", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3kmr\| PDB=3kmr \| SCENE= }}

-	~~Authors: Bourguet, W., Teyssier, C.~~	+	===Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment===

-	Description: Crystal structure of RARalpha ligand binding domain in complex with an agonist ligand (Am580) and a coactivator fragment

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Dec 23 09~~:22:~~47 2009~~''	+	==About this Structure==
		+	3KMR is a 2 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KMR OCA].
		+	[[Category: Histone acetyltransferase]]
		+	[[Category: Homo sapiens]]
		+	[[Category: Bourguet, W.]]
		+	[[Category: Teyssier, C.]]
		+	[[Category: Activator]]
		+	[[Category: Acyltransferase]]
		+	[[Category: Alternative splicing]]
		+	[[Category: Chromosomal rearrangement]]
		+	[[Category: Dna-binding]]
		+	[[Category: Isopeptide bond]]
		+	[[Category: Metal-binding]]
		+	[[Category: Nuclear receptor transcription factor ligand binding domain]]
		+	[[Category: Nucleus]]
		+	[[Category: Phosphoprotein]]
		+	[[Category: Polymorphism]]
		+	[[Category: Proto-oncogene]]
		+	[[Category: Receptor]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription regulation]]
		+	[[Category: Transferase]]
		+	[[Category: Ubl conjugation]]
		+	[[Category: Zinc]]
		+	[[Category: Zinc-finger]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 2 08:38:27 2010''