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==Crystal structure of human CUL3 N-terminal domain bound to KEAP1 BTB and 3-box==
==Crystal structure of human CUL3 N-terminal domain bound to KEAP1 BTB and 3-box==
<StructureSection load='5nlb' size='340' side='right' caption='[[5nlb]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
<StructureSection load='5nlb' size='340' side='right'caption='[[5nlb]], [[Resolution|resolution]] 3.45&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5nlb]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NLB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NLB FirstGlance]. <br>
<table><tr><td colspan='2'>[[5nlb]] is a 2 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=5NLB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NLB FirstGlance]. <br>
</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=5nlb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nlb OCA], [http://pdbe.org/5nlb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nlb RCSB], [http://www.ebi.ac.uk/pdbsum/5nlb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nlb ProSAT]</span></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]] 3.45&#8491;</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=5nlb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nlb OCA], [https://pdbe.org/5nlb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nlb RCSB], [https://www.ebi.ac.uk/pdbsum/5nlb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nlb ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[http://omim.org/entry/614496 614496]]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref> 
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref> 
[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN]  
== References ==
 
<references/>
==See Also==
*[[Cullin 3D structures|Cullin 3D structures]]
*[[Galectin 3D structures|Galectin 3D structures]]
*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]]
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Adamson, R]]
[[Category: Homo sapiens]]
[[Category: Arrowsmith, C H]]
[[Category: Large Structures]]
[[Category: Bartual, S G]]
[[Category: Adamson R]]
[[Category: Borkowska, O]]
[[Category: Arrowsmith CH]]
[[Category: Bountra, C]]
[[Category: Bartual SG]]
[[Category: Bullock, A]]
[[Category: Borkowska O]]
[[Category: Burgess-Brown, N A]]
[[Category: Bountra C]]
[[Category: Chalk, R]]
[[Category: Bullock A]]
[[Category: Counago, R M]]
[[Category: Burgess-Brown NA]]
[[Category: Delft, F von]]
[[Category: Chalk R]]
[[Category: Dixon-Clarke, S E]]
[[Category: Dixon-Clarke SE]]
[[Category: Edwards, A M]]
[[Category: Edwards AM]]
[[Category: Kopec, J]]
[[Category: Kopec J]]
[[Category: Krojer, T]]
[[Category: Krojer T]]
[[Category: Mackinnon, S]]
[[Category: Mackinnon S]]
[[Category: Mathea, S]]
[[Category: Mathea S]]
[[Category: Newman, J A]]
[[Category: Newman JA]]
[[Category: Sethi, R]]
[[Category: Pinkas DM]]
[[Category: Velupillai, S]]
[[Category: Sethi R]]
[[Category: E3 ubiquitin ligase]]
[[Category: Velupillai S]]
[[Category: Ligase]]
[[Category: Von Delft F]]

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