2j5e - Revision history

OCA at 14:34, 13 December 2023

2023-12-13T14:34:49Z

←Older revision		Revision as of 14:34, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2j5e' size='340' side='right'caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2j5e' size='340' side='right'caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J5E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J5E FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=CL:CHLORIDE+ION'>CL</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='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene~~></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</div></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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [https://pdbe.org/2j5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [https://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e 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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [https://pdbe.org/2j5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [https://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e 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]]
Line 40:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Receptor protein-tyrosine kinase]]~~	+	[[Category: Eck MJ]]
-	[[Category: Eck~~, M J~~]]	+	[[Category: Yun C-H]]
-	[[Category: Yun, C H]]	+
-	~~[[Category: 13-jab]]~~	+
-	~~[[Category: Alternative splicing]]~~	+
-	~~[[Category: Anti-oncogene]]~~	+
-	~~[[Category: Atp-binding]]~~	+
-	~~[[Category: Cell cycle]]~~	+
-	~~[[Category: Disease mutation]]~~	+
-	~~[[Category: Egfr]]~~	+
-	~~[[Category: Epidermal growth factor]]~~	+
-	~~[[Category: Glycoprotein]]~~	+
-	~~[[Category: Irreversible inhibitor]]~~	+
-	~~[[Category: Kinase]]~~	+
-	~~[[Category: Membrane]]~~	+
-	~~[[Category: Nucleotide-binding]]~~	+
-	~~[[Category: Phosphorylation]]~~	+
-	~~[[Category: Polymorphism]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Tyrosine-protein kinase]]~~	+
-	~~[[Category: Ubl conjugation]]~~	+
-	~~[[Category: Wild-type~~]]	+

OCA at 08:01, 19 January 2022

2022-01-19T08:01:53Z

OCA at 07:40, 15 April 2020

2020-04-15T07:40:44Z

←Older revision		Revision as of 07:40, 15 April 2020
Line 1:		Line 1:

	==Crystal structure of EGFR kinase domain in complex with an irreversible inhibitor 13-jab==		==Crystal structure of EGFR kinase domain in complex with an irreversible inhibitor 13-jab==
-	<StructureSection load='2j5e' size='340' side='right' caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>	+	<StructureSection load='2j5e' size='340' side='right'caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2J5E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2J5E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://pdbe.org/2j5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e 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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://pdbe.org/2j5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 35:		Line 35:

	==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 41:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Eck, M J]]		[[Category: Eck, M J]]

OCA at 06:55, 11 July 2018

2018-07-11T06:55:53Z

←Older revision		Revision as of 06:55, 11 July 2018
Line 1:		Line 1:
-	==~~CRYSTAL STRUCTURE OF~~ EGFR ~~KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR~~ 13-~~JAB~~==	+
		+	==Crystal structure of EGFR kinase domain in complex with an irreversible inhibitor 13-jab==
	<StructureSection load='2j5e' size='340' side='right' caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2j5e' size='340' side='right' caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 7:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://pdbe.org/2j5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e 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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://pdbe.org/2j5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j5/2j5e_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j5/2j5e_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 44:		Line 45:
	[[Category: Yun, C H]]		[[Category: Yun, C H]]
	[[Category: 13-jab]]		[[Category: 13-jab]]
		+	[[Category: Alternative splicing]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
Line 56:		Line 58:
	[[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]]
		+	[[Category: Ubl conjugation]]
	[[Category: Wild-type]]		[[Category: Wild-type]]

OCA at 01:39, 10 February 2016

2016-02-10T01:39:29Z

←Older revision		Revision as of 01:39, 10 February 2016
Line 21:		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=2j5e ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 04:05, 11 September 2015

2015-09-11T04:05:54Z

←Older revision		Revision as of 04:05, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2j5e' size='340' side='right' caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2j5e' size='340' side='right' caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J5E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J5E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e 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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://pdbe.org/2j5e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		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 2j5e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
	[[Category: Eck, M J]]		[[Category: Eck, M J]]

OCA at 18:01, 19 January 2015

2015-01-19T18:01:55Z

←Older revision		Revision as of 18:01, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J5E FirstGlance]. <br>		<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J5E FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e 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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e 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 40:		Line 40:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]
-	[[Category: Eck, M J.]]	+	[[Category: Eck, M J]]
-	[[Category: Yun, C H.]]	+	[[Category: Yun, C H]]
	[[Category: 13-jab]]		[[Category: 13-jab]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]

OCA at 10:41, 30 September 2014

2014-09-30T10:41:19Z

←Older revision		Revision as of 10:41, 30 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_2j5e\| PDB=2j5e \| SCENE= }}~~	+	==CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 13-JAB==
-	===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 13-JAB===	+	<StructureSection load='2j5e' size='340' side='right' caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>
-	{~~{ABSTRACT_PUBMED_17334377}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J5E FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [http://www.ebi.ac.uk/pdbsum/2j5e 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/j5/2j5e_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 ==
		+	As key components in nearly every signal transduction pathway, protein kinases are attractive targets for the regulation of cellular signaling by small-molecule inhibitors. We report the structure-guided development of 6-acrylamido-4-anilinoquinazoline irreversible kinase inhibitors that potently and selectively target rationally designed kinases bearing two selectivity elements that are not found together in any wild-type kinase: an electrophile-targeted cysteine residue and a glycine gatekeeper residue. Cocrystal structures of two irreversible quinazoline inhibitors bound to either epidermal growth factor receptor (EGFR) or engineered c-Src show covalent inhibitor binding to the targeted cysteine (Cys797 in EGFR and Cys345 in engineered c-Src). To accommodate the new covalent bond, the quinazoline core adopts positions that are different from those seen in kinase structures with reversible quinazoline inhibitors. Based on these structures, we developed a fluorescent 6-acrylamido-4-anilinoquinazoline affinity probe to report the fraction of kinase necessary for cellular signaling, and we used these reagents to quantitate the relationship between EGFR stimulation by EGF and its downstream outputs-Akt, Erk1 and Erk2.

-	~~==Function==~~	+	Structure-guided development of affinity probes for tyrosine kinases using chemical genetics.,Blair JA, Rauh D, Kung C, Yun CH, Fan QW, Rode H, Zhang C, Eck MJ, Weiss WA, Shokat KM Nat Chem Biol. 2007 Apr;3(4):229-38. Epub 2007 Mar 4. PMID:17334377<ref>PMID:17334377</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>
-	~~[[2j5e]] 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=2J5E 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:017334377</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 22:08, 24 March 2013

2013-03-24T22:08:25Z

←Older revision		Revision as of 22:08, 24 March 2013
Line 1:		Line 1:
-	[[Image:2j5e.png\|left\|200px]]
-
	{{STRUCTURE_2j5e\| PDB=2j5e \| SCENE= }}		{{STRUCTURE_2j5e\| PDB=2j5e \| SCENE= }}
-
	===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 13-JAB===		===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 13-JAB===
		+	{{ABSTRACT_PUBMED_17334377}}

-	~~{{ABSTRACT_PUBMED_17334377}}~~	+	==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:017334377</ref><references group="xtra"/>	+	<ref group="xtra">PMID:017334377</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Receptor protein-tyrosine kinase]]		[[Category: Receptor protein-tyrosine kinase]]

OCA at 15:52, 20 October 2012

2012-10-20T15:52:01Z

←Older revision		Revision as of 15:52, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[2j5e]] 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=2J5E OCA].	+	[[2j5e]] 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=2J5E OCA].

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

←Older revision		Revision as of 08:01, 19 January 2022
Line 3:		Line 3:
	<StructureSection load='2j5e' size='340' side='right'caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2j5e' size='340' side='right'caption='[[2j5e]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2J5E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[2j5e]] 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=2J5E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J5E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CY0:S-{3-[(4-ANILINOQUINAZOLIN-6-YL)AMINO]-3-OXOPROPYL}-L-CYSTEINE'>CY0</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dnq\|1dnq]], [[1dnr\|1dnr]], [[1ivo\|1ivo]], [[1m14\|1m14]], [[1m17\|1m17]], [[1mox\|1mox]], [[1nql\|1nql]], [[1xkk\|1xkk]], [[1yy9\|1yy9]], [[1z9i\|1z9i]], [[2gs2\|2gs2]], [[2gs7\|2gs7]], [[2itn\|2itn]], [[2ito\|2ito]], [[2itp\|2itp]], [[2itq\|2itq]], [[2itt\|2itt]], [[2itu\|2itu]], [[2itv\|2itv]], [[2itw\|2itw]], [[2itx\|2itx]], [[2ity\|2ity]], [[2itz\|2itz]], [[2j5f\|2j5f]]</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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [~~http~~://pdbe.org/2j5e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e 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=2j5e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5e OCA], [https://pdbe.org/2j5e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j5e RCSB], [https://www.ebi.ac.uk/pdbsum/2j5e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j5e 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]]