1x2r

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==Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2==
==Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2==
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<StructureSection load='1x2r' size='340' side='right' caption='[[1x2r]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
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<StructureSection load='1x2r' size='340' side='right'caption='[[1x2r]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[1x2r]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X2R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1X2R FirstGlance]. <br>
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<table><tr><td colspan='2'>[[1x2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X2R FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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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]] 1.7&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1x2j|1x2j]]</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=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<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=1x2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x2r OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1x2r RCSB], [http://www.ebi.ac.uk/pdbsum/1x2r PDBsum], [http://www.topsan.org/Proteins/RSGI/1x2r TOPSAN]</span></td></tr>
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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=1x2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x2r OCA], [https://pdbe.org/1x2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x2r RCSB], [https://www.ebi.ac.uk/pdbsum/1x2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x2r ProSAT], [https://www.topsan.org/Proteins/RSGI/1x2r TOPSAN]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE]] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref> [[http://www.uniprot.org/uniprot/NF2L2_MOUSE NF2L2_MOUSE]] Transcription activator that binds to antioxidant response (ARE) elements in the promoter regions of target genes. Important for the coordinated up-regulation of genes in response to oxidative stress. May be involved in the transcriptional activation of genes of the beta-globin cluster by mediating enhancer activity of hypersensitive site 2 of the beta-globin locus control region.<ref>PMID:9887101</ref>
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[https://www.uniprot.org/uniprot/KEAP1_MOUSE KEAP1_MOUSE] Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x2/1x2r_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x2/1x2r_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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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=1x2r ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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<div class="pdbe-citations 1x2r" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Kelch-like ECH-associated protein 1|Kelch-like ECH-associated protein 1]]
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*[[Kelch-like protein|Kelch-like protein]]
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*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Kang, M I]]
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[[Category: Kang M-I]]
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[[Category: Kobayashi, A]]
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[[Category: Kobayashi A]]
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[[Category: Nakamura, Y]]
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[[Category: Nakamura Y]]
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[[Category: Ohta, T]]
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[[Category: Ohta T]]
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[[Category: Ohtsuji, M]]
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[[Category: Ohtsuji M]]
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[[Category: Padmanabhan, B]]
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[[Category: Padmanabhan B]]
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[[Category: Structural genomic]]
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[[Category: Scharlock M]]
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[[Category: Scharlock, M]]
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[[Category: Tong KI]]
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[[Category: Tong, K I]]
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[[Category: Yamamoto M]]
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[[Category: Yamamoto, M]]
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[[Category: Yokoyama S]]
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[[Category: Yokoyama, S]]
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[[Category: Beta propeller]]
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[[Category: National project on protein structural and functional analyse]]
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[[Category: Nppsfa]]
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[[Category: Rsgi]]
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[[Category: Transcription]]
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Current revision

Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2

PDB ID 1x2r

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