7p2k
From Proteopedia
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<StructureSection load='7p2k' size='340' side='right'caption='[[7p2k]]' scene=''> | <StructureSection load='7p2k' size='340' side='right'caption='[[7p2k]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full | + | <table><tr><td colspan='2'>[[7p2k]] 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=7P2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7P2K FirstGlance]. <br> |
| - | </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=7p2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2k OCA], [https://pdbe.org/7p2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2k RCSB], [https://www.ebi.ac.uk/pdbsum/7p2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2k ProSAT]</span></td></tr> | + | </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=7p2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7p2k OCA], [https://pdbe.org/7p2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7p2k RCSB], [https://www.ebi.ac.uk/pdbsum/7p2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7p2k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Single nucleotide polymorphisms (SNPs) are genetic variations which can play a vital role in the study of human health. SNP studies are often used to identify point mutations that are associated with diseases. Arkadia (RNF111) is an E3 ubiquitin ligase that enhances transforming growth factor-beta (TGF-beta) signaling by targeting negative regulators for degradation. Dysregulation of the TGF-beta pathway is implicated in cancer because it exhibits tumor suppressive activity in normal cells while in tumor cells it promotes invasiveness and metastasis. Tauhe SNP CGT > TGT generated an amino-acid (aa) substitution of Arginine 957 to Cysteine on the enzymatic RING domain of Arkadia. This was more prevalent in a tumor than in a normal tissue sample of a patient with colorectal cancer. This prompted us to investigate the effect of this mutation in the structure and activity of Arkadia RING. We used nuclear magnetic resonance (NMR) to analyze at an atomic-level the structural and dynamic properties of the R957C Arkadia RING domain, while ubiquitination and luciferase assays provided information about its enzymatic functionality. Our study showed that the R957C mutation changed the electrostatic properties of the RING domain however, without significant effects on the structure of its core region. However, the functional studies revealed that the R957C Arkadia exhibits significantly increased enzymatic activity supporting literature data that Arkadia within tumor cells promotes aggressive and metastatic behavior. | ||
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| + | Impact of a Single Nucleotide Polymorphism on the 3D Protein Structure and Ubiquitination Activity of E3 Ubiquitin Ligase Arkadia.,Birkou M, Raptis V, Marousis KD, Tsevis A, Bourikas K, Bentrop D, Episkopou V, Spyroulias GA Front Mol Biosci. 2022 Feb 23;9:844129. doi: 10.3389/fmolb.2022.844129., eCollection 2022. PMID:35281275<ref>PMID:35281275</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7p2k" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Bentrop D]] | [[Category: Bentrop D]] | ||
Revision as of 11:19, 14 June 2023
Solution NMR Structure of Arginine to Cysteine mutant of Arkadia RING domain.
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