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| | <StructureSection load='4wip' size='340' side='right'caption='[[4wip]], [[Resolution|resolution]] 2.69Å' scene=''> | | <StructureSection load='4wip' size='340' side='right'caption='[[4wip]], [[Resolution|resolution]] 2.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4wip]] is a 3 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=4WIP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4WIP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4wip]] 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=4WIP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WIP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene></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]] 2.691Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pz8|3pz8]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DVL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4wip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wip OCA], [https://pdbe.org/4wip PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wip RCSB], [https://www.ebi.ac.uk/pdbsum/4wip PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wip ProSAT]</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=4wip FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wip OCA], [http://pdbe.org/4wip PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4wip RCSB], [http://www.ebi.ac.uk/pdbsum/4wip PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4wip ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DVL2_HUMAN DVL2_HUMAN]] Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes (By similarity).<ref>PMID:19252499</ref> | + | [https://www.uniprot.org/uniprot/DVL2_HUMAN DVL2_HUMAN] Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes (By similarity).<ref>PMID:19252499</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bienz, M]] | + | [[Category: Bienz M]] |
| - | [[Category: Chin, J W]] | + | [[Category: Chin JW]] |
| - | [[Category: Fiedler, M]] | + | [[Category: Fiedler M]] |
| - | [[Category: Madrzak, J]] | + | [[Category: Madrzak J]] |
| - | [[Category: Polymer signaling ubiquitin-like]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
DVL2_HUMAN Participates in Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling. Plays a role both in canonical and non-canonical Wnt signaling. Plays a role in the signal transduction pathways mediated by multiple Wnt genes (By similarity).[1]
Publication Abstract from PubMed
Dishevelled relays Wnt signals from the plasma membrane to different cytoplasmic effectors. Its signalling activity depends on its DIX domain, which undergoes head-to-tail polymerization to assemble signalosomes. The DIX domain is ubiquitinated in vivo at multiple lysines, which can be antagonized by various deubiquitinases (DUBs) including the CYLD tumour suppressor that attenuates Wnt signalling. Here, we generate milligram quantities of pure human Dvl2 DIX domain mono-ubiquitinated at two lysines (K54 and K58) by genetically encoded orthogonal protection with activated ligation (GOPAL), to investigate their effect on DIX polymerization. We show that the ubiquitination of DIX at K54 blocks its polymerization in solution, whereas DIX58-Ub remains oligomerization-competent. DUB profiling identified 28 DUBs that cleave DIX-ubiquitin conjugates, half of which prefer, or are specific for, DIX54-Ub, including Cezanne and CYLD. These DUBs thus have the potential to promote Dvl polymerization and signalosome formation, rather than antagonize it as previously thought for CYLD.
Ubiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization.,Madrzak J, Fiedler M, Johnson CM, Ewan R, Knebel A, Bienz M, Chin JW Nat Commun. 2015 Apr 24;6:6718. doi: 10.1038/ncomms7718. PMID:25907794[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang Y, Appleton BA, Wiesmann C, Lau T, Costa M, Hannoush RN, Sidhu SS. Inhibition of Wnt signaling by Dishevelled PDZ peptides. Nat Chem Biol. 2009 Apr;5(4):217-9. Epub 2009 Mar 1. PMID:19252499 doi:10.1038/nchembio.152
- ↑ Madrzak J, Fiedler M, Johnson CM, Ewan R, Knebel A, Bienz M, Chin JW. Ubiquitination of the Dishevelled DIX domain blocks its head-to-tail polymerization. Nat Commun. 2015 Apr 24;6:6718. doi: 10.1038/ncomms7718. PMID:25907794 doi:http://dx.doi.org/10.1038/ncomms7718
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