4rix - Revision history

OCA at 17:50, 20 September 2023

2023-09-20T17:50:39Z

← Older revision		Revision as of 17:50, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rix]] 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=4RIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RIX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rix]] 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=4RIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RIX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 3.1Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [https://pdbe.org/4rix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [https://www.ebi.ac.uk/pdbsum/4rix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix 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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [https://pdbe.org/4rix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [https://www.ebi.ac.uk/pdbsum/4rix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix ProSAT]</span></td></tr>
	</table>		</table>

OCA at 06:58, 2 March 2023

2023-03-02T06:58:53Z

← Older revision		Revision as of 06:58, 2 March 2023
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	<StructureSection load='4rix' size='340' side='right'caption='[[4rix]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='4rix' size='340' side='right'caption='[[4rix]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rix]] 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=4RIX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RIX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rix]] 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=4RIX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RIX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4riw\|4riw]], [[4riy\|4riy]]</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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [https://pdbe.org/4rix PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [https://www.ebi.ac.uk/pdbsum/4rix PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix ProSAT]</span></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB3, HER3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EGFR ([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/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [~~http~~://pdbe.org/4rix PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rix PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[~~[http~~://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN]] Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:[~~http~~://omim.org/entry/607598 607598]]; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology.<ref>PMID:17701904</ref> [[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[http://omim.org/entry/211980 211980]]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis.		[https://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN] Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:[https://omim.org/entry/607598 607598]; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology.<ref>PMID:17701904</ref>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN]] Binds and is activated by neuregulins and NTAK.<ref>PMID:15358134</ref> [[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> Isoform 2 may act as an antagonist of EGF action.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref>		[https://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN] Binds and is activated by neuregulins and NTAK.<ref>PMID:15358134</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
	*[[Epidermal ~~Growth Factor Receptor~~\|Epidermal ~~Growth Factor Receptor~~]]		*[[Epidermal growth factor receptor 3D structures\|Epidermal growth factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Receptor protein-tyrosine kinase]]~~		[[Category: Jura N]]
	[[Category: Jura, N]]		[[Category: Littlefield P]]
	[[Category: Littlefield, P]]		[[Category: Liu L]]
	[[Category: Liu, L]]
	~~[[Category: Atp binding]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Membrane]]~~
	~~[[Category: Pseudokinase]]~~
	~~[[Category: Receptor tyrosine kinase]]~~
	~~[[Category: Transferase~~]]

OCA at 09:41, 1 May 2019

2019-05-01T09:41:23Z

← Older revision		Revision as of 09:41, 1 May 2019
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	==Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation==		==Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation==
	<StructureSection load='4rix' size='340' side='right' caption='[[4rix]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='4rix' size='340' side='right'caption='[[4rix]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rix]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RIX FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rix]] 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=4RIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RIX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4riw\|4riw]], [[4riy\|4riy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4riw\|4riw]], [[4riy\|4riy]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ERBB3, HER3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EGFR ([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/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [http://pdbe.org/4rix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [http://www.ebi.ac.uk/pdbsum/4rix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix 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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [http://pdbe.org/4rix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [http://www.ebi.ac.uk/pdbsum/4rix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Jura, N]]		[[Category: Jura, N]]

OCA at 09:20, 5 August 2016

2016-08-05T09:20:53Z

← Older revision		Revision as of 09:20, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation==		==Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation==
	<StructureSection load='4rix' size='340' side='right' caption='[[4rix]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='4rix' size='340' side='right' caption='[[4rix]], [[Resolution\|resolution]] 3.10Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4riw\|4riw]], [[4riy\|4riy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4riw\|4riw]], [[4riy\|4riy]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [http://www.ebi.ac.uk/pdbsum/4rix 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=4rix FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rix OCA], [http://pdbe.org/4rix PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rix RCSB], [http://www.ebi.ac.uk/pdbsum/4rix PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rix ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	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 4rix" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Epidermal Growth Factor Receptor\|Epidermal Growth Factor Receptor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:56, 17 December 2014

2014-12-17T08:56:19Z

← Older revision		Revision as of 08:56, 17 December 2014
Line 12:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN]] Binds and is activated by neuregulins and NTAK.<ref>PMID:15358134</ref> [[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> Isoform 2 may act as an antagonist of EGF action.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref>		[[http://www.uniprot.org/uniprot/ERBB3_HUMAN ERBB3_HUMAN]] Binds and is activated by neuregulins and NTAK.<ref>PMID:15358134</ref> [[http://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref> Isoform 2 may act as an antagonist of EGF action.<ref>PMID:7657591</ref> <ref>PMID:11602604</ref> <ref>PMID:12873986</ref> <ref>PMID:10805725</ref> <ref>PMID:11116146</ref> <ref>PMID:11483589</ref> <ref>PMID:17115032</ref> <ref>PMID:21258366</ref> <ref>PMID:12297050</ref> <ref>PMID:12620237</ref> <ref>PMID:15374980</ref> <ref>PMID:19560417</ref> <ref>PMID:20837704</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			The human epidermal growth factor receptor (HER) tyrosine kinases homo- and heterodimerize to activate downstream signaling pathways. HER3 is a catalytically impaired member of the HER family that contributes to the development of several human malignancies and is mutated in a subset of cancers. HER3 signaling depends on heterodimerization with a catalytically active partner, in particular epidermal growth factor receptor (EGFR) (the founding family member, also known as HER1) or HER2. The activity of homodimeric complexes of catalytically active HER family members depends on allosteric activation between the two kinase domains. To determine the structural basis for HER3 signaling through heterodimerization with a catalytically active HER family member, we solved the crystal structure of the heterodimeric complex formed by the isolated kinase domains of EGFR and HER3. The structure showed HER3 as an allosteric activator of EGFR and revealed a conserved role of the allosteric mechanism in activation of HER family members through heterodimerization. To understand the effects of cancer-associated HER3 mutations at the molecular level, we solved the structures of two kinase domains of HER3 mutants, each in a heterodimeric complex with the kinase domain of EGFR. These structures, combined with biochemical analysis and molecular dynamics simulations, indicated that the cancer-associated HER3 mutations enhanced the allosteric activator function of HER3 by redesigning local interactions at the dimerization interface.

			Structural analysis of the EGFR/HER3 heterodimer reveals the molecular basis for activating HER3 mutations.,Littlefield P, Liu L, Mysore V, Shan Y, Shaw DE, Jura N Sci Signal. 2014 Dec 2;7(354):ra114. doi: 10.1126/scisignal.2005786. PMID:25468994<ref>PMID:25468994</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:26, 10 December 2014

2014-12-10T16:26:07Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation==
+<StructureSection load='4rix' size='340' side='right' caption='[[4rix]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
-The entry 4rix is ON HOLD
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4rix]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RIX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RIX FirstGlance]. <br>
-Authors: Littlefield, P., Liu, L., Jura, N.
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4riw|4riw]], [[4riy|4riy]]</td></tr>
-Description: Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>

OCA: Protected "4rix" [edit=sysop:move=sysop]

2014-10-20T09:30:48Z

Protected "4rix" [edit=sysop:move=sysop]

← Older revision	Revision as of 09:30, 20 October 2014
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4rix is ON HOLD Authors: Littlefield, P., Liu, L., Jura, N. Description: Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the...

2014-10-20T09:30:46Z

New page: '''Unreleased structure''' The entry 4rix is ON HOLD Authors: Littlefield, P., Liu, L., Jura, N. Description: Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the...

New page

'''Unreleased structure'''

The entry 4rix is ON HOLD

Authors: Littlefield, P., Liu, L., Jura, N.

Description: Crystal structure of an EGFR/HER3 kinase domain heterodimer containing the cancer-associated HER3-Q790R mutation