2jit - Revision history

OCA at 14:50, 13 December 2023

2023-12-13T14:50:36Z

← Older revision		Revision as of 14:50, 13 December 2023
Line 3:		Line 3:
	<StructureSection load='2jit' size='340' side='right'caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2jit' size='340' side='right'caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2jit]] is a 2 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=2JIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JIT FirstGlance]. <br>		<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JIT FirstGlance]. <br>
	</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</div></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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 ~~and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [https://pdbe.org/2jit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [https://www.ebi.ac.uk/pdbsum/2jit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit 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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [https://pdbe.org/2jit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [https://www.ebi.ac.uk/pdbsum/2jit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit 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 38:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Human~~]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	~~[[Category: Transferase]]~~		[[Category: Eck MJ]]
	[[Category: Eck~~, M J~~]]		[[Category: Greulich H]]
	[[Category: Greulich, H]]		[[Category: Mengwasser KE]]
	[[Category: Mengwasser~~, K E~~]]		[[Category: Meyerson M]]
	[[Category: Meyerson, M]]		[[Category: Toms AV]]
	[[Category: Toms~~, A V~~]]		[[Category: Wong K-K]]
	[[Category: Wong, K K]]		[[Category: Woo MS]]
	[[Category: Woo~~, M S~~]]		[[Category: Yun C-H]]
	[[Category: Yun, C H]]
	~~[[Category: Anti-oncogene]]~~
	~~[[Category: Atp-binding]]~~
	~~[[Category: Cell cycle]]~~
	~~[[Category: Disease mutation]]~~
	~~[[Category: Egfr]]~~
	~~[[Category: Epidermal growth factor]]~~
	~~[[Category: Kinase]]~~
	~~[[Category: Nucleotide-binding]]~~
	~~[[Category: Phosphorylation]]~~
	~~[[Category: Receptor]]~~
	~~[[Category: T790m]]~~
	~~[[Category: Tyrosine-protein kinase~~]]

OCA at 08:11, 19 January 2022

2022-01-19T08:11:51Z

OCA at 07:52, 15 April 2020

2020-04-15T07:52:35Z

← Older revision		Revision as of 07:52, 15 April 2020
Line 1:		Line 1:

	==Crystal structure of EGFR kinase domain T790M mutation==		==Crystal structure of EGFR kinase domain T790M mutation==
	<StructureSection load='2jit' size='340' side='right' caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2jit' size='340' side='right'caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2JIT FirstGlance]. <br>		<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2JIT FirstGlance]. <br>
	</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>		</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://pdbe.org/2jit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit 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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://pdbe.org/2jit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 33:		Line 33:

	==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 39:		Line 39:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Eck, M J]]		[[Category: Eck, M J]]

OCA at 06:48, 11 July 2018

2018-07-11T06:48:58Z

← Older revision		Revision as of 06:48, 11 July 2018
Line 1:		Line 1:
	==~~CRYSTAL STRUCTURE OF~~ EGFR ~~KINASE DOMAIN~~ T790M ~~MUTATION~~==
			==Crystal structure of EGFR kinase domain T790M mutation==
	<StructureSection load='2jit' size='340' side='right' caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2jit' size='340' side='right' caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
Line 5:		Line 6:
	</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>		</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://pdbe.org/2jit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit 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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://pdbe.org/2jit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 15:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ji/2jit_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ji/2jit_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>
	</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=2jit ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 14:32, 11 September 2015

2015-09-11T14:32:28Z

← Older revision		Revision as of 14:32, 11 September 2015
Line 2:		Line 2:
	<StructureSection load='2jit' size='340' side='right' caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2jit' size='340' side='right' caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JIT FirstGlance]. <br>		<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JIT FirstGlance]. <br>
	</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>		</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit 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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://pdbe.org/2jit PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 29:		Line 29:
	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 2jit" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 36:		Line 37:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Eck, M J]]		[[Category: Eck, M J]]

OCA at 15:27, 19 January 2015

2015-01-19T15:27:05Z

← Older revision		Revision as of 15:27, 19 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JIT FirstGlance]. <br>		<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JIT FirstGlance]. <br>
	</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>		</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>
	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit 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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit 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 38:		Line 38:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]
	[[Category: Eck, M J.]]		[[Category: Eck, M J]]
	[[Category: Greulich, H.]]		[[Category: Greulich, H]]
	[[Category: Mengwasser, K E.]]		[[Category: Mengwasser, K E]]
	[[Category: Meyerson, M.]]		[[Category: Meyerson, M]]
	[[Category: Toms, A V.]]		[[Category: Toms, A V]]
	[[Category: Wong, K K.]]		[[Category: Wong, K K]]
	[[Category: Woo, M S.]]		[[Category: Woo, M S]]
	[[Category: Yun, C H.]]		[[Category: Yun, C H]]
	[[Category: Anti-oncogene]]		[[Category: Anti-oncogene]]
	[[Category: Atp-binding]]		[[Category: Atp-binding]]
Line 57:		Line 57:
	[[Category: Receptor]]		[[Category: Receptor]]
	[[Category: T790m]]		[[Category: T790m]]
	~~[[Category: Transferase]]~~
	[[Category: Tyrosine-protein kinase]]		[[Category: Tyrosine-protein kinase]]

OCA at 08:42, 30 September 2014

2014-09-30T08:42:55Z

← Older revision		Revision as of 08:42, 30 September 2014
Line 1:		Line 1:
	~~{{STRUCTURE_2jit\| PDB=2jit \| SCENE= }}~~		==CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN T790M MUTATION==
	===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN T790M MUTATION===		<StructureSection load='2jit' size='340' side='right' caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>
	~~{{ABSTRACT_PUBMED_18227510}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2JIT FirstGlance]. <br>
	==Disease==		</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>
			<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [http://www.ebi.ac.uk/pdbsum/2jit 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/ji/2jit_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 ==
			Lung cancers caused by activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to small molecule tyrosine kinase inhibitors (TKIs), but the efficacy of these agents is often limited because of the emergence of drug resistance conferred by a second mutation, T790M. Threonine 790 is the "gatekeeper" residue, an important determinant of inhibitor specificity in the ATP binding pocket. The T790M mutation has been thought to cause resistance by sterically blocking binding of TKIs such as gefitinib and erlotinib, but this explanation is difficult to reconcile with the fact that it remains sensitive to structurally similar irreversible inhibitors. Here, we show by using a direct binding assay that T790M mutants retain low-nanomolar affinity for gefitinib. Furthermore, we show that the T790M mutation activates WT EGFR and that introduction of the T790M mutation increases the ATP affinity of the oncogenic L858R mutant by more than an order of magnitude. The increased ATP affinity is the primary mechanism by which the T790M mutation confers drug resistance. Crystallographic analysis of the T790M mutant shows how it can adapt to accommodate tight binding of diverse inhibitors, including the irreversible inhibitor HKI-272, and also suggests a structural mechanism for catalytic activation. We conclude that the T790M mutation is a "generic" resistance mutation that will reduce the potency of any ATP-competitive kinase inhibitor and that irreversible inhibitors overcome this resistance simply through covalent binding, not as a result of an alternative binding mode.

	~~==Function==~~		The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP.,Yun CH, Mengwasser KE, Toms AV, Woo MS, Greulich H, Wong KK, Meyerson M, Eck MJ Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5. Epub 2008 Jan 28. PMID:18227510<ref>PMID:18227510</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>
	~~[[2jit]] is~~ a ~~2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:/~~/~~oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT 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:018227510</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:44, 24 March 2013

2013-03-24T19:44:40Z

← Older revision		Revision as of 19:44, 24 March 2013
Line 1:		Line 1:
	~~[[Image:2jit.png\|left\|200px]]~~

	{{STRUCTURE_2jit\| PDB=2jit \| SCENE= }}		{{STRUCTURE_2jit\| PDB=2jit \| SCENE= }}
			===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN T790M MUTATION===
			{{ABSTRACT_PUBMED_18227510}}

	===~~CRYSTAL STRUCTURE OF~~ EGFR ~~KINASE DOMAIN T790M MUTATION===~~		==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.

	~~{{ABSTRACT_PUBMED_18227510}}~~		==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:018227510</ref><references group="xtra"/>		<ref group="xtra">PMID:018227510</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]

OCA at 19:36, 20 October 2012

2012-10-20T19:36:40Z

← Older revision		Revision as of 19:36, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
	[[2jit]] is a 2 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=2JIT OCA].		[[2jit]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA].

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

OCA at 07:55, 27 July 2012

2012-07-27T07:55:09Z

← Older revision		Revision as of 07:55, 27 July 2012
Line 1:		Line 1:
	[[Image:2jit.png\|left\|200px]]		[[Image:2jit.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2jit", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
	~~-->~~
	{{STRUCTURE_2jit\| PDB=2jit \| SCENE= }}		{{STRUCTURE_2jit\| PDB=2jit \| SCENE= }}

	===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN T790M MUTATION===		===CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN T790M MUTATION===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_18227510}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 18227510 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_18227510}}		{{ABSTRACT_PUBMED_18227510}}

Line 22:		Line 11:

	==See Also==		==See Also==
	*[[Epidermal Growth Factor Receptor]]		*[[Epidermal Growth Factor Receptor\|Epidermal Growth Factor Receptor]]

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~18227510~~</ref><references group="xtra"/>		<ref group="xtra">PMID:018227510</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Transferase]]		[[Category: Transferase]]

← Older revision		Revision as of 08:11, 19 January 2022
Line 3:		Line 3:
	<StructureSection load='2jit' size='340' side='right'caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='2jit' size='340' side='right'caption='[[2jit]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2jit]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JIT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=2JIT FirstGlance]. <br>		<table><tr><td colspan='2'>[[2jit]] is a 2 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=2JIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JIT FirstGlance]. <br>
	</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</td></tr>		</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]], [[2j5e\|2j5e]], [[2j5f\|2j5f]], [[2j6m\|2j6m]], [[2jiu\|2jiu]], [[2jiv\|2jiv]]</div></td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Transferase Transferase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Transferase Transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [~~http~~://pdbe.org/2jit PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2jit PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit 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=2jit FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jit OCA], [https://pdbe.org/2jit PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jit RCSB], [https://www.ebi.ac.uk/pdbsum/2jit PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jit 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]]