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| {{STRUCTURE_3op0| PDB=3op0 | SCENE= }}
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| ===Crystal structure of Cbl-c (Cbl-3) TKB domain in complex with EGFR pY1069 peptide===
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| ==Disease== | | ==Crystal structure of Cbl-c (Cbl-3) TKB domain in complex with EGFR pY1069 peptide== |
| [[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. | | <StructureSection load='3op0' size='340' side='right'caption='[[3op0]], [[Resolution|resolution]] 2.52Å' scene=''> |
| | | == Structural highlights == |
| ==Function== | | <table><tr><td colspan='2'>[[3op0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OP0 FirstGlance]. <br> |
| [[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> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.52Å</td></tr> |
| | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr> |
| ==About this Structure==
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3op0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3op0 OCA], [https://pdbe.org/3op0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3op0 RCSB], [https://www.ebi.ac.uk/pdbsum/3op0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3op0 ProSAT]</span></td></tr> |
| [[3op0]] is a 4 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=3OP0 OCA]. | | </table> |
| | | == Function == |
| ==Reference== | | [https://www.uniprot.org/uniprot/CBLC_HUMAN CBLC_HUMAN] Regulator of EGFR mediated signal transduction. |
| <references group="xtra"/><references/>
| | __TOC__ |
| | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| [[Category: Arrowsmith, C H.]] | | [[Category: Large Structures]] |
| [[Category: Ayinampudi, V.]] | | [[Category: Arrowsmith CH]] |
| [[Category: Bountra, C.]] | | [[Category: Ayinampudi V]] |
| [[Category: Bullock, A.]] | | [[Category: Bountra C]] |
| [[Category: Canning, P.]] | | [[Category: Bullock A]] |
| [[Category: Chaikuad, A.]] | | [[Category: Canning P]] |
| [[Category: Cooper, C D.O.]] | | [[Category: Chaikuad A]] |
| [[Category: Delft, F von.]]
| | [[Category: Cooper CDO]] |
| [[Category: Edwards, A M.]] | | [[Category: Edwards AM]] |
| [[Category: Guo, K.]] | | [[Category: Guo K]] |
| [[Category: Krojer, T.]] | | [[Category: Krojer T]] |
| [[Category: Muniz, J R.C.]] | | [[Category: Muniz JRC]] |
| [[Category: SGC, Structural Genomics Consortium.]]
| | [[Category: Ugochukwu E]] |
| [[Category: Ugochukwu, E.]] | | [[Category: Vollmar M]] |
| [[Category: Vollmar, M.]] | | [[Category: Weigelt J]] |
| [[Category: Weigelt, J.]] | | [[Category: Von Delft F]] |
| [[Category: Sgc]] | |
| [[Category: Sh3-binding protein]]
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| [[Category: Signal transduction protein]]
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| [[Category: Signaling protein-signaling protein regulator complex]]
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| [[Category: Structural genomic]]
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| [[Category: Structural genomics consortium]]
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