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4hxi

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==Crystal structure of KLHL3/Cul3 complex==
==Crystal structure of KLHL3/Cul3 complex==
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<StructureSection load='4hxi' size='340' side='right' caption='[[4hxi]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
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<StructureSection load='4hxi' size='340' side='right'caption='[[4hxi]], [[Resolution|resolution]] 3.51&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4hxi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HXI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HXI FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4hxi]] 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=4HXI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HXI FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KLHL3, KIAA1129 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CUL3, KIAA0617 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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</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=4hxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hxi OCA], [https://pdbe.org/4hxi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hxi RCSB], [https://www.ebi.ac.uk/pdbsum/4hxi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hxi ProSAT]</span></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=4hxi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hxi OCA], [http://pdbe.org/4hxi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hxi RCSB], [http://www.ebi.ac.uk/pdbsum/4hxi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hxi ProSAT]</span></td></tr>
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</table>
</table>
== Disease ==
== Disease ==
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[[http://www.uniprot.org/uniprot/KLHL3_HUMAN KLHL3_HUMAN]] Pseudohypoaldosteronism type 2D. The disease is caused by mutations affecting the gene represented in this entry. [[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>
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[https://www.uniprot.org/uniprot/KLHL3_HUMAN KLHL3_HUMAN] Pseudohypoaldosteronism type 2D. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/KLHL3_HUMAN KLHL3_HUMAN]] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron. The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation.<ref>PMID:14528312</ref> <ref>PMID:23387299</ref> <ref>PMID:23453970</ref> <ref>PMID:23665031</ref> <ref>PMID:23576762</ref> <ref>PMID:22406640</ref> [[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>
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[https://www.uniprot.org/uniprot/KLHL3_HUMAN KLHL3_HUMAN] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron. The BCR(KLHL3) complex acts by mediating ubiquitination of WNK4, an inhibitor of potassium channel KCNJ1, leading to WNK4 degradation.<ref>PMID:14528312</ref> <ref>PMID:23387299</ref> <ref>PMID:23453970</ref> <ref>PMID:23665031</ref> <ref>PMID:23576762</ref> <ref>PMID:22406640</ref>
==See Also==
==See Also==
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*[[Cullin|Cullin]]
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*[[Cullin 3D structures|Cullin 3D structures]]
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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: Human]]
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[[Category: Homo sapiens]]
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[[Category: Ji, A X]]
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[[Category: Large Structures]]
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[[Category: Prive, G G]]
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[[Category: Ji AX]]
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[[Category: Btb-back]]
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[[Category: Prive GG]]
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[[Category: Protein binding]]
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[[Category: Protein-protein interaction]]
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Revision as of 08:24, 9 November 2022

Crystal structure of KLHL3/Cul3 complex

PDB ID 4hxi

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