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| | ==Solution structure of RNF126 N-terminal zinc finger domain== | | ==Solution structure of RNF126 N-terminal zinc finger domain== |
| - | <StructureSection load='2n9o' size='340' side='right'caption='[[2n9o]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2n9o' size='340' side='right'caption='[[2n9o]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2n9o]] 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=2N9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N9O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2n9o]] 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=2N9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N9O 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2n9p|2n9p]]</div></td></tr> | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RNF126 ([https://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=2n9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n9o OCA], [https://pdbe.org/2n9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n9o RCSB], [https://www.ebi.ac.uk/pdbsum/2n9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n9o 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=2n9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n9o OCA], [https://pdbe.org/2n9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n9o RCSB], [https://www.ebi.ac.uk/pdbsum/2n9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n9o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RN126_HUMAN RN126_HUMAN]] E3 ubiquitin-protein ligase that regulates several biological processes through ubiquitination of various target proteins. Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates. Through their polyubiquitination, may play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4. May also be part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. May provide the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the mislocalized proteins and their targeting to the proteasome (PubMed:24981174). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564).[UniProtKB:Q91YL2]<ref>PMID:23277564</ref> <ref>PMID:24275455</ref> <ref>PMID:24981174</ref> <ref>PMID:23026136</ref>
| + | [https://www.uniprot.org/uniprot/RN126_HUMAN RN126_HUMAN] E3 ubiquitin-protein ligase that regulates several biological processes through ubiquitination of various target proteins. Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates. Through their polyubiquitination, may play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4. May also be part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. May provide the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the mislocalized proteins and their targeting to the proteasome (PubMed:24981174). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564).[UniProtKB:Q91YL2]<ref>PMID:23277564</ref> <ref>PMID:24275455</ref> <ref>PMID:24981174</ref> <ref>PMID:23026136</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: Isaacson, R L]] | + | [[Category: Isaacson RL]] |
| - | [[Category: Krysztofinska, E M]] | + | [[Category: Krysztofinska EM]] |
| - | [[Category: Martinez-Lumbreras, S]] | + | [[Category: Martinez-Lumbreras S]] |
| - | [[Category: Thapaliya, A]] | + | [[Category: Thapaliya A]] |
| - | [[Category: E3 ligase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Function
RN126_HUMAN E3 ubiquitin-protein ligase that regulates several biological processes through ubiquitination of various target proteins. Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates. Through their polyubiquitination, may play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4. May also be part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. May provide the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the mislocalized proteins and their targeting to the proteasome (PubMed:24981174). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564).[UniProtKB:Q91YL2][1] [2] [3] [4]
Publication Abstract from PubMed
RNF126 is an E3 ubiquitin ligase that collaborates with the BAG6 sortase complex to ubiquitinate hydrophobic substrates in the cytoplasm that are destined for proteasomal recycling. Composed of a trimeric complex of BAG6, TRC35 and UBL4A the BAG6 sortase is also associated with SGTA, a co-chaperone from which it can obtain hydrophobic substrates. Here we solve the solution structure of the RNF126 zinc finger domain in complex with the BAG6 UBL domain. We also characterise an interaction between RNF126 and UBL4A and analyse the competition between SGTA and RNF126 for the N-terminal BAG6 binding site. This work sheds light on the sorting mechanism of the BAG6 complex and its accessory proteins which, together, decide the fate of stray hydrophobic proteins in the aqueous cytoplasm.
Structural and functional insights into the E3 ligase, RNF126.,Krysztofinska EM, Martinez-Lumbreras S, Thapaliya A, Evans NJ, High S, Isaacson RL Sci Rep. 2016 May 19;6:26433. doi: 10.1038/srep26433. PMID:27193484[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Delker RK, Zhou Y, Strikoudis A, Stebbins CE, Papavasiliou FN. Solubility-based genetic screen identifies RING finger protein 126 as an E3 ligase for activation-induced cytidine deaminase. Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):1029-34. doi:, 10.1073/pnas.1214538110. Epub 2012 Dec 31. PMID:23277564 doi:http://dx.doi.org/10.1073/pnas.1214538110
- ↑ Smith CJ, McGlade CJ. The ubiquitin ligase RNF126 regulates the retrograde sorting of the cation-independent mannose 6-phosphate receptor. Exp Cell Res. 2014 Jan 15;320(2):219-32. doi: 10.1016/j.yexcr.2013.11.013. Epub, 2013 Nov 23. PMID:24275455 doi:http://dx.doi.org/10.1016/j.yexcr.2013.11.013
- ↑ Rodrigo-Brenni MC, Gutierrez E, Hegde RS. Cytosolic quality control of mislocalized proteins requires RNF126 recruitment to Bag6. Mol Cell. 2014 Jul 17;55(2):227-37. doi: 10.1016/j.molcel.2014.05.025. Epub 2014 , Jun 26. PMID:24981174 doi:http://dx.doi.org/10.1016/j.molcel.2014.05.025
- ↑ Zhi X, Zhao D, Wang Z, Zhou Z, Wang C, Chen W, Liu R, Chen C. E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation. Cancer Res. 2013 Jan 1;73(1):385-94. doi: 10.1158/0008-5472.CAN-12-0562. Epub, 2012 Oct 1. PMID:23026136 doi:http://dx.doi.org/10.1158/0008-5472.CAN-12-0562
- ↑ Krysztofinska EM, Martinez-Lumbreras S, Thapaliya A, Evans NJ, High S, Isaacson RL. Structural and functional insights into the E3 ligase, RNF126. Sci Rep. 2016 May 19;6:26433. doi: 10.1038/srep26433. PMID:27193484 doi:http://dx.doi.org/10.1038/srep26433
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