3vrp

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==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-EGFR peptide==
==Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-EGFR peptide==
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<StructureSection load='3vrp' size='340' side='right' caption='[[3vrp]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
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<StructureSection load='3vrp' size='340' side='right'caption='[[3vrp]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3vrp]] 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=3VRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VRP FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3vrp]] 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=3VRP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VRP FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.52&#8491;</td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vrn|3vrn]], [[3vro|3vro]], [[3vrq|3vrq]], [[3vrr|3vrr]]</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vrp OCA], [https://pdbe.org/3vrp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vrp RCSB], [https://www.ebi.ac.uk/pdbsum/3vrp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vrp ProSAT]</span></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CBLC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<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=3vrp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vrp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vrp RCSB], [http://www.ebi.ac.uk/pdbsum/3vrp PDBsum]</span></td></tr>
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</table>
</table>
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== Disease ==
 
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[[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 ==
== Function ==
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[[http://www.uniprot.org/uniprot/CBLC_HUMAN CBLC_HUMAN]] Regulator of EGFR mediated signal transduction. [[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>
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[https://www.uniprot.org/uniprot/CBLC_HUMAN CBLC_HUMAN] Regulator of EGFR mediated signal transduction.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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<div class="pdbe-citations 3vrp" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Large Structures]]
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[[Category: Isozaki, Y]]
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[[Category: Isozaki Y]]
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[[Category: Nakagawa, A]]
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[[Category: Nakagawa A]]
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[[Category: Suzuki, M]]
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[[Category: Suzuki M]]
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[[Category: Takeshita, K]]
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[[Category: Takeshita K]]
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[[Category: Tezuka, T]]
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[[Category: Tezuka T]]
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[[Category: Yamamoto, T]]
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[[Category: Yamamoto T]]
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[[Category: Yamanashi, Y]]
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[[Category: Yamanashi Y]]
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[[Category: Yamashita, E]]
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[[Category: Yamashita E]]
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[[Category: Calcium-binding ef hand]]
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[[Category: Divergent sh2 domain]]
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[[Category: Protein binding-transferase complex]]
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[[Category: Ptb domain]]
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[[Category: Regulator of egfr mediated signal transduction]]
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[[Category: Ubiquitously expressed]]
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Current revision

Crystal structure of the tyrosine kinase binding domain of Cbl-c in complex with phospho-EGFR peptide

PDB ID 3vrp

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