2bz8

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{{Seed}}
 
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[[Image:2bz8.png|left|200px]]
 
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==N-terminal Sh3 domain of CIN85 bound to Cbl-b peptide==
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The line below this paragraph, containing "STRUCTURE_2bz8", creates the "Structure Box" on the page.
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<StructureSection load='2bz8' size='340' side='right'caption='[[2bz8]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2bz8]] is a 3 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=2BZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BZ8 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2&#8491;</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=NA:SODIUM+ION'>NA</scene></td></tr>
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{{STRUCTURE_2bz8| PDB=2bz8 | SCENE= }}
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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=2bz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bz8 OCA], [https://pdbe.org/2bz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bz8 RCSB], [https://www.ebi.ac.uk/pdbsum/2bz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bz8 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SH3K1_HUMAN SH3K1_HUMAN] Adapter protein involved in regulating diverse signal transduction pathways. Involved in the regulation of endocytosis and lysosomal degradation of ligand-induced receptor tyrosine kinases, including EGFR and MET/hepatocyte growth factor receptor, through a association with CBL and endophilins. The association with CBL, and thus the receptor internalization, may inhibited by an interaction with PDCD6IP and/or SPRY2. Involved in regulation of ligand-dependent endocytosis of the IgE receptor. Attenuates phosphatidylinositol 3-kinase activity by interaction with its regulatory subunit (By similarity). May be involved in regulation of cell adhesion; promotes the interaction between TTK2B and PDCD6IP. May be involved in the regulation of cellular stress response via the MAPK pathways through its interaction with MAP3K4. Is involved in modulation of tumor necrosis factor mediated apoptosis. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration.<ref>PMID:12177062</ref> <ref>PMID:11894095</ref> <ref>PMID:11894096</ref> <ref>PMID:12771190</ref> <ref>PMID:12734385</ref> <ref>PMID:15090612</ref> <ref>PMID:16256071</ref> <ref>PMID:15707590</ref> <ref>PMID:16177060</ref> <ref>PMID:21834987</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bz/2bz8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2bz8 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The ubiquitin ligases c-Cbl and Cbl-b play a crucial role in receptor downregulation by mediating multiple monoubiquitination of receptors and promoting their sorting for lysosomal degradation. Their function is modulated through interactions with regulatory proteins including CIN85 and PIX, which recognize a proline-arginine motif in Cbl and thus promote or inhibit receptor endocytosis. We report the structures of SH3 domains of CIN85 and beta-PIX in complex with a proline-arginine peptide from Cbl-b. Both structures reveal a heterotrimeric complex containing two SH3 domains held together by a single peptide. Trimerization also occurs in solution and is facilitated by the pseudo-symmetrical peptide sequence. Moreover, ternary complexes of CIN85 and Cbl are formed in vivo and are important for the ability of Cbl to promote epidermal growth factor receptor (EGFR) downregulation. These results provide molecular explanations for a novel mechanism by which Cbl controls receptor downregulation.
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===N-TERMINAL SH3 DOMAIN OF CIN85 BOUND TO CBL-B PEPTIDE===
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Cbl promotes clustering of endocytic adaptor proteins.,Jozic D, Cardenes N, Deribe YL, Moncalian G, Hoeller D, Groemping Y, Dikic I, Rittinger K, Bravo J Nat Struct Mol Biol. 2005 Nov;12(11):972-9. PMID:16228008<ref>PMID:16228008</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_16228008}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2bz8" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16228008 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16228008}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2BZ8 is a [[Protein complex]] structure of sequences 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=2BZ8 OCA].
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==Reference==
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Cbl promotes clustering of endocytic adaptor proteins., Jozic D, Cardenes N, Deribe YL, Moncalian G, Hoeller D, Groemping Y, Dikic I, Rittinger K, Bravo J, Nat Struct Mol Biol. 2005 Nov;12(11):972-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16228008 16228008]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Bravo, J.]]
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[[Category: Bravo J]]
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[[Category: Cardenes, N.]]
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[[Category: Cardenes N]]
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[[Category: Moncalian, G.]]
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[[Category: Moncalian G]]
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[[Category: Cbl ubiquitin ligase]]
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[[Category: Cin85 adaptor protein]]
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[[Category: Endocytosis]]
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[[Category: Sh3 domain]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:27:34 2008''
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Current revision

N-terminal Sh3 domain of CIN85 bound to Cbl-b peptide

PDB ID 2bz8

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