1zvd

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[[Image:1zvd.png|left|200px]]
 
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==Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain==
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The line below this paragraph, containing "STRUCTURE_1zvd", creates the "Structure Box" on the page.
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<StructureSection load='1zvd' size='340' side='right'caption='[[1zvd]], [[Resolution|resolution]] 2.10&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'>[[1zvd]] 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=1ZVD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZVD 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]] 2.1&#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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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{{STRUCTURE_1zvd| PDB=1zvd | 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=1zvd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zvd OCA], [https://pdbe.org/1zvd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zvd RCSB], [https://www.ebi.ac.uk/pdbsum/1zvd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zvd ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SMUF2_HUMAN SMUF2_HUMAN] E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD1 and SMAD7 in order to trigger their ubiquitination and proteasome-dependent degradation. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with SCYE1. Forms a stable complex with the TGF-beta receptor-mediated phosphorylated SMAD2 and SMAD3. In this way, SMAD2 may recruit substrates, such as SNON, for ubiquitin-mediated degradation. Enhances the inhibitory activity of SMAD7 and reduces the transcriptional activity of SMAD2. Coexpression of SMURF2 with SMAD1 results in considerable decrease in steady-state level of SMAD1 protein and a smaller decrease of SMAD2 level.<ref>PMID:11389444</ref> <ref>PMID:12717440</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/zv/1zvd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1zvd 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 conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins.
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===Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain===
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Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain.,Ogunjimi AA, Briant DJ, Pece-Barbara N, Le Roy C, Di Guglielmo GM, Kavsak P, Rasmussen RK, Seet BT, Sicheri F, Wrana JL Mol Cell. 2005 Aug 5;19(3):297-308. PMID:16061177<ref>PMID:16061177</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_16061177}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 1zvd" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16061177 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16061177}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[1zvd]] 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=1ZVD OCA].
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==Reference==
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<ref group="xtra">PMID:016061177</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Briant, D J.]]
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[[Category: Large Structures]]
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[[Category: Guglielmo, G M.Di.]]
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[[Category: Briant DJ]]
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[[Category: Kavsak, P.]]
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[[Category: Di Guglielmo GM]]
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[[Category: Ogunjimi, A A.]]
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[[Category: Kavsak P]]
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[[Category: Pece-Barbara, N.]]
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[[Category: Le Roy C]]
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[[Category: Rasmussen, R K.]]
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[[Category: Ogunjimi AA]]
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[[Category: Roy, C Le.]]
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[[Category: Pece-Barbara N]]
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[[Category: Seet, B T.]]
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[[Category: Rasmussen RK]]
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[[Category: Sicheri, F.]]
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[[Category: Seet BT]]
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[[Category: Wrana, J L.]]
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[[Category: Sicheri F]]
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[[Category: Ligase]]
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[[Category: Wrana JL]]
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[[Category: Tgfbeta]]
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[[Category: Ubiquitin ligasecatalytic mechanism]]
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[[Category: X-ray crystal structure]]
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Current revision

Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain

PDB ID 1zvd

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