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| | ==Solution structure of Arkadia RING-H2 finger domain== | | ==Solution structure of Arkadia RING-H2 finger domain== |
| - | <StructureSection load='2kiz' size='340' side='right'caption='[[2kiz]], [[NMR_Ensembles_of_Models | 31 NMR models]]' scene=''> | + | <StructureSection load='2kiz' size='340' side='right'caption='[[2kiz]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kiz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kiz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KIZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 31 models</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF111 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2kiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kiz OCA], [https://pdbe.org/2kiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kiz RCSB], [https://www.ebi.ac.uk/pdbsum/2kiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kiz ProSAT]</span></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=2kiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kiz OCA], [https://pdbe.org/2kiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kiz RCSB], [https://www.ebi.ac.uk/pdbsum/2kiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kiz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RN111_HUMAN RN111_HUMAN]] Acts in the NODAL pathway of mesoderm patterning during embryonic development. Acts downstream AXIN1 as an E3 ubiquitin-protein ligase which promotes the ubiquitination of inhibitory SMADs such as SMAD7, induces their proteasomal degradation and thereby enhances the transcriptional activity of TGF-beta and BMP. Activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Associates with UBE2D2 as an E2 enzyme.<ref>PMID:14657019</ref> <ref>PMID:16601693</ref> <ref>PMID:17591695</ref> <ref>PMID:22411132</ref>
| + | [https://www.uniprot.org/uniprot/RN111_HUMAN RN111_HUMAN] Acts in the NODAL pathway of mesoderm patterning during embryonic development. Acts downstream AXIN1 as an E3 ubiquitin-protein ligase which promotes the ubiquitination of inhibitory SMADs such as SMAD7, induces their proteasomal degradation and thereby enhances the transcriptional activity of TGF-beta and BMP. Activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Associates with UBE2D2 as an E2 enzyme.<ref>PMID:14657019</ref> <ref>PMID:16601693</ref> <ref>PMID:17591695</ref> <ref>PMID:22411132</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kiz_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ki/2kiz_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bentrop, D]] | + | [[Category: Bentrop D]] |
| - | [[Category: Chasapis, C T]] | + | [[Category: Chasapis CT]] |
| - | [[Category: Episkopou, V]] | + | [[Category: Episkopou V]] |
| - | [[Category: Kandias, N G]] | + | [[Category: Kandias NG]] |
| - | [[Category: Spyroulias, G A]] | + | [[Category: Spyroulias GA]] |
| - | [[Category: Arkadia]]
| + | |
| - | [[Category: E3 ligase]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Ring-h2 finger]]
| + | |
| - | [[Category: Zinc-finger]]
| + | |
| - | [[Category: Zn binding domain]]
| + | |
| Structural highlights
Function
RN111_HUMAN Acts in the NODAL pathway of mesoderm patterning during embryonic development. Acts downstream AXIN1 as an E3 ubiquitin-protein ligase which promotes the ubiquitination of inhibitory SMADs such as SMAD7, induces their proteasomal degradation and thereby enhances the transcriptional activity of TGF-beta and BMP. Activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Associates with UBE2D2 as an E2 enzyme.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Arkadia (Rnf111), an E3 Ubiquitin (Ub) ligase, amplifies TGF-beta signaling responses by targeting for degradation of the negative regulators Smad6/7 and the SnoN/Ski transcriptional repressors when they block the TGF-beta effectors Smad2/3. The E3 ligase activity of Arkadia depends on its C-terminal RING-H2 domain that constitutes the docking site for the E2 Ub-conjugating enzyme carrying the activated Ub. We determined the nuclear magnetic resonance solution structure of Arkadia's RING-H2 domain and revealed a (beta)betabetaalpha fold, fully consistent with the expected "cross-brace" mode of Zn(II)-ligation. In addition, the interaction of the Arkadia RING-H2 domain with its E2 partner enzyme (UbcH5b) was examined through chemical shift perturbation. Proteins 2012. (c) 2012 Wiley Periodicals, Inc.
NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase.,Chasapis CT, Kandias NG, Episkopou V, Bentrop D, Spyroulias GA Proteins. 2012 May;80(5):1484-9. doi: 10.1002/prot.24048. Epub 2012 Mar 13. PMID:22411132[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, Ebina M, Nukiwa T, Miyazawa K, Imamura T, Miyazono K. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003 Dec 15;22(24):6458-70. PMID:14657019 doi:http://dx.doi.org/10.1093/emboj/cdg632
- ↑ Liu W, Rui H, Wang J, Lin S, He Y, Chen M, Li Q, Ye Z, Zhang S, Chan SC, Chen YG, Han J, Lin SC. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006 Apr 19;25(8):1646-58. Epub 2006 Apr 6. PMID:16601693 doi:7601057
- ↑ Levy L, Howell M, Das D, Harkin S, Episkopou V, Hill CS. Arkadia activates Smad3/Smad4-dependent transcription by triggering signal-induced SnoN degradation. Mol Cell Biol. 2007 Sep;27(17):6068-83. Epub 2007 Jun 25. PMID:17591695 doi:http://dx.doi.org/10.1128/MCB.00664-07
- ↑ Chasapis CT, Kandias NG, Episkopou V, Bentrop D, Spyroulias GA. NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase. Proteins. 2012 May;80(5):1484-9. doi: 10.1002/prot.24048. Epub 2012 Mar 13. PMID:22411132 doi:http://dx.doi.org/10.1002/prot.24048
- ↑ Chasapis CT, Kandias NG, Episkopou V, Bentrop D, Spyroulias GA. NMR-based insights into the conformational and interaction properties of Arkadia RING-H2 E3 Ub ligase. Proteins. 2012 May;80(5):1484-9. doi: 10.1002/prot.24048. Epub 2012 Mar 13. PMID:22411132 doi:http://dx.doi.org/10.1002/prot.24048
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