2itp - Revision history

OCA at 14:25, 13 December 2023

OCA — Wed, 13 Dec 2023 14:25:03 GMT

←Older revision		Revision as of 14:25, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2itp' size='340' side='right'caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>		<StructureSection load='2itp' size='340' side='right'caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2itp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ITP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ITP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ITP FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=AEE:6-{4~~-[~~(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-~~[~~(1R)-1-PHENYLETHYL~~]~~-7H-PYRROLO[~~2~~,3-D]PYRIMIDIN-4-AMINE'>AEE</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]] 2.74Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>
-	~~<tr~~ id~~='activity'><td class~~="~~sblockLbl~~"><~~b>Activity:</b></td><td class~~=~~"sblockDat"><span class~~=~~'plainlinks'>[https~~:~~//en.wikipedia.org/wiki/Receptor_protein~~-~~tyrosine_kinase Receptor protein~~-~~tyrosine kinase~~]~~, with EC number~~ [~~https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [https://pdbe.org/2itp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [https://www.ebi.ac.uk/pdbsum/2itp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp 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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [https://pdbe.org/2itp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [https://www.ebi.ac.uk/pdbsum/2itp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[https://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/EGFR_HUMAN EGFR_HUMAN] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[https://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.
	== Function ==		== Function ==
-	[[https://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/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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Boggon TJ]]
-	[[Category: Boggon~~, T J~~]]	+	[[Category: Eck MJ]]
-	[[Category: Eck~~, M J~~]]	+	[[Category: Greulich H]]
-	[[Category: Greulich, H]]	+	[[Category: Li Y]]
-	[[Category: Li, Y]]	+	[[Category: Meyerson M]]
-	[[Category: Meyerson, M]]	+	[[Category: Woo S]]
-	[[Category: Woo, S]]	+	[[Category: Yun C-H]]
-	[[Category: Yun, C H]]	+
-	~~[[Category: Aee788]]~~	+
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Anti-oncogene]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Egfr]]~~	+
-	~~[[Category: Epidermal growth factor]]~~	+
-	~~[[Category: G719]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Tyrosine-protein kinase~~]]	+

OCA at 10:31, 12 January 2022

OCA — Wed, 12 Jan 2022 10:31:46 GMT

OCA at 07:50, 8 April 2020

OCA — Wed, 08 Apr 2020 07:50:27 GMT

←Older revision		Revision as of 07:50, 8 April 2020
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	==Crystal structure of EGFR kinase domain G719S mutation in complex with AEE788==		==Crystal structure of EGFR kinase domain G719S mutation in complex with AEE788==
-	<StructureSection load='2itp' size='340' side='right' caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>	+	<StructureSection load='2itp' size='340' side='right'caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2ITP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2ITP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://pdbe.org/2itp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp ProSAT]</span></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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://pdbe.org/2itp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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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/>
Line 40:		Line 40:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Boggon, T J]]		[[Category: Boggon, T J]]

OCA at 07:51, 4 July 2018

OCA — Wed, 04 Jul 2018 07:51:21 GMT

←Older revision		Revision as of 07:51, 4 July 2018
Line 1:		Line 1:
-	==~~CRYSTAL STRUCTURE OF~~ EGFR ~~KINASE DOMAIN~~ G719S ~~MUTATION IN COMPLEX WITH~~ AEE788==	+
		+	==Crystal structure of EGFR kinase domain G719S mutation in complex with AEE788==
	<StructureSection load='2itp' size='340' side='right' caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>		<StructureSection load='2itp' size='340' side='right' caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://pdbe.org/2itp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp 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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://pdbe.org/2itp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/it/2itp_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/it/2itp_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>
Line 48:		Line 49:
	[[Category: Yun, C H]]		[[Category: Yun, C H]]
	[[Category: Aee788]]		[[Category: Aee788]]
		+	[[Category: Alternative splicing]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
Line 60:		Line 62:
	[[Category: Nucleotide-binding]]		[[Category: Nucleotide-binding]]
	[[Category: Phosphorylation]]		[[Category: Phosphorylation]]
		+	[[Category: Polymorphism]]
	[[Category: Receptor]]		[[Category: Receptor]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
	[[Category: Tyrosine-protein kinase]]		[[Category: Tyrosine-protein kinase]]

OCA at 14:10, 7 February 2016

OCA — Sun, 07 Feb 2016 14:10:43 GMT

←Older revision		Revision as of 14:10, 7 February 2016
Line 20:		Line 20:
	<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=2itp ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 02:15, 10 September 2015

OCA — Thu, 10 Sep 2015 02:15:18 GMT

←Older revision		Revision as of 02:15, 10 September 2015
Line 2:		Line 2:
	<StructureSection load='2itp' size='340' side='right' caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>		<StructureSection load='2itp' size='340' side='right' caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ITP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ITP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp 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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://pdbe.org/2itp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 30:		Line 30:
	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 2itp" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Boggon, T J]]		[[Category: Boggon, T J]]

OCA at 07:54, 16 January 2015

OCA — Fri, 16 Jan 2015 07:54:56 GMT

←Older revision		Revision as of 07:54, 16 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ITP FirstGlance]. <br>		<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ITP FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>
-	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp 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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[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.		[[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.
Line 39:		Line 39:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Boggon, T J.]]	+	[[Category: Boggon, T J]]
-	[[Category: Eck, M J.]]	+	[[Category: Eck, M J]]
-	[[Category: Greulich, H.]]	+	[[Category: Greulich, H]]
-	[[Category: Li, Y.]]	+	[[Category: Li, Y]]
-	[[Category: Meyerson, M.]]	+	[[Category: Meyerson, M]]
-	[[Category: Woo, S.]]	+	[[Category: Woo, S]]
-	[[Category: Yun, C H.]]	+	[[Category: Yun, C H]]
	[[Category: Aee788]]		[[Category: Aee788]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]

OCA at 09:11, 30 September 2014

OCA — Tue, 30 Sep 2014 09:11:34 GMT

←Older revision		Revision as of 09:11, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2itp\| PDB=2itp \| SCENE= }}~~	+	==CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788==
-	===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788===	+	<StructureSection load='2itp' size='340' side='right' caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>
-	{~~{ABSTRACT_PUBMED_17349580}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ITP FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>
		+	<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [http://www.ebi.ac.uk/pdbsum/2itp PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
	[[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.		[[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.
		+	== Function ==
		+	[[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>
		+	== 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/it/2itp_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 ==
		+	Mutations in the EGFR kinase are a cause of non-small-cell lung cancer. To understand their mechanism of activation and effects on drug binding, we studied the kinetics of the L858R and G719S mutants and determined their crystal structures with inhibitors including gefitinib, AEE788, and a staurosporine. We find that the mutations activate the kinase by disrupting autoinhibitory interactions, and that they accelerate catalysis as much as 50-fold in vitro. Structures of inhibitors in complex with both wild-type and mutant kinases reveal similar binding modes for gefitinib and AEE788, but a marked rotation of the staurosporine in the G719S mutant. Strikingly, direct binding measurements show that gefitinib binds 20-fold more tightly to the L858R mutant than to the wild-type enzyme.

-	~~==Function==~~	+	Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity.,Yun CH, Boggon TJ, Li Y, Woo MS, Greulich H, Meyerson M, Eck MJ Cancer Cell. 2007 Mar;11(3):217-27. PMID:17349580<ref>PMID:17349580</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>	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[2itp]] is~~ a ~~1 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=2ITP OCA].~~	+	</div>

	==See Also==		==See Also==
	*[[Epidermal Growth Factor Receptor\|Epidermal Growth Factor Receptor]]		*[[Epidermal Growth Factor Receptor\|Epidermal Growth Factor Receptor]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:017349580</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 20:26, 24 March 2013

OCA — Sun, 24 Mar 2013 20:26:56 GMT

←Older revision		Revision as of 20:26, 24 March 2013
Line 1:		Line 1:
-	[[Image:2itp.png\|left\|200px]]
-
	{{STRUCTURE_2itp\| PDB=2itp \| SCENE= }}		{{STRUCTURE_2itp\| PDB=2itp \| SCENE= }}
-
	===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788===		===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN G719S MUTATION IN COMPLEX WITH AEE788===
		+	{{ABSTRACT_PUBMED_17349580}}

-	~~{{ABSTRACT_PUBMED_17349580}}~~	+	==Disease==
		+	[[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.
		+
		+	==Function==
		+	[[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>

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

	==Reference==		==Reference==
-	<ref group="xtra">PMID:017349580</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017349580</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 06:52, 20 October 2012

OCA — Sat, 20 Oct 2012 06:52:51 GMT

←Older revision		Revision as of 06:52, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[2itp]] is a 1 chain structure ~~of [[Epidermal Growth Factor Receptor]]~~ 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=2ITP OCA].	+	[[2itp]] is a 1 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=2ITP OCA].

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

←Older revision		Revision as of 10:31, 12 January 2022
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	<StructureSection load='2itp' size='340' side='right'caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>		<StructureSection load='2itp' size='340' side='right'caption='[[2itp]], [[Resolution\|resolution]] 2.74Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2itp]] is a 1 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=2ITP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2ITP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2itp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ITP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ITP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEE:6-{4-[(4-ETHYLPIPERAZIN-1-YL)METHYL]PHENYL}-N-[(1R)-1-PHENYLETHYL]-7H-PYRROLO[2,3-D]PYRIMIDIN-4-AMINE'>AEE</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xkk\|1xkk]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]]</div></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'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://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~~://proteopedia.org/fgij/fg.htm?mol=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [~~http~~://pdbe.org/2itp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2itp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp 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=2itp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2itp OCA], [https://pdbe.org/2itp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2itp RCSB], [https://www.ebi.ac.uk/pdbsum/2itp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2itp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~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/EGFR_HUMAN EGFR_HUMAN]] Defects in EGFR are associated with lung cancer (LNCR) [MIM:[https://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.
	== Function ==		== Function ==
-	[[~~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/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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]