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Kelch-like protein: Difference between revisions

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<StructureSection load='1x2r' size='340' side='right' caption='Human Kelch-like protein 1 (Keap1) Kelch domain (grey) complex with NRF2 Neh2 peptide (light green) and sulfate (PDB code [[1x2r]])' scene=''>
<StructureSection load='' size='450' side='right' caption='Human Kelch-like protein 1 (Keap1) Kelch domain (cyan) complex with NRF2 Neh2 peptide (green) and sulfate (PDB code [[1x2r]])' scene='70/706701/Cv/1'>
== Function ==
== Function ==
'''Kelch-like proteins''' (KLHL) contain multiple Kelch motifs.  This motif is about 50 residues long and forms a four-stranded β-sheet blade.  Six to eight such blades form a circular β-propeller domain.  β-propellers are involved in protein-protein interactions.  The N-terminal of KLHL contains other protein domains like BTB (Broad-Tramtrack-Bric-a-brac) which is also involved in protein-protein interactions<ref>PMID:23676014</ref>.
'''Kelch-like proteins''' (KLHL) contain multiple Kelch motifs.  This motif is about 50 residues long and forms a four-stranded β-sheet blade.  <scene name='70/706701/Cv/6'>Six to eight such blades form a circular β-propeller domain</scene>.  β-propellers are involved in protein-protein interactions.  The N-terminal of KLHL contains other protein domains like BTB (Broad-Tramtrack-Bric-a-brac) which is also involved in protein-protein interactions<ref>PMID:23676014</ref>.<br />
*'''KLHL2''' '''KLHL11''' is a component of the cullin-RING based E3 ubiquitin-protein ligase system.<br />
*'''KLHL3''' and '''KLHL7''' '''KLHL10''' are substrate-specific adapters of the cullin-RING based E3 ubiquitin-protein ligase system.<br />
*'''KLHL12''' may play a role in collagen export.<br />
*'''KLHL16 or gigaxonin''' plays a role in neurofilament architecture.<br />
*'''KLHL19 (Keap1)''' interacts with the Neh2 peptide of NRF2.<br />


== Disease ==
== Disease ==
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== Relevance ==
== Relevance ==
'''KLHL19 (Keap1)''' interacts with the Neh2 peptide of NRF2.  NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target.
NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target.


== Structural highlights ==
== Structural highlights ==
The interaction of Keap1 with Neh2 is through the first Glu in the latter's ETGE motif<ref>PMID:16507366</ref>.
The <scene name='70/706701/Cv/7'>interaction of Keap1 with Neh2 is through the first Glu in the latter's ETGE motif</scene><ref>PMID:16507366</ref>. <scene name='70/706701/Cv/8'>All interactions of Keap1 with Neh2</scene>. Water molecules shown as red spheres.
 
</StructureSection>


== 3D Structures of Kelch-like protein ==
== 3D Structures of Kelch-like protein ==
[[Kelch-like protein 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Kelch-like protein 2
 
**[[2xn4]] – hKLHL2 Kelch domain – human <br />
 
*Kelch-like protein 3
 
**[[4chb]], [[4ch9]] – hKLHL3 Kelch domain + serine/threonine protein kinas WNK4 peptide <br />
**[[4hxi]] – hKLHL3 BTB-BACK domain (mutant) + cullin-3 N terminal <br />
 
*Kelch-like protein 7
 
**[[3ii7]] – hKLHL7 Kelch domain  <br />
 
*Kelch-like protein 11
 
**[[3i3n]] – hKLHL11 BTB-BACK domain <br />
**[[4ap2]], [[4apf]] – hKLHL11 BTB-BACK domain + cullin-3 N terminal <br />
 
*Kelch-like protein 12
 
**[[2vpj]] – hKLHL12 Kelch domain  <br />
 
*Kelch-like protein 16 (gigaxonin)
 
**[[3hve]] – hKLHL16  <br />
**[[2ppi]] – hKLHL16 BTB domain  <br />
 
*Kelch-like protein 19 (kelch-like ECH-associated protein 1; Keap1)
 
**[[1u6d]], [[1zgk]], [[4ifj]] – hKeap1 Kelch domain  <br />
**[[3zgd]] – hKeap1 Kelch domain (mutant) <br />
**[[4cxi]], [[4cxj]] – hKeap1 BTB domain (mutant) <br />
**[[1x2j]] – mKeap1 Kelch domain - mouse <br />
 
*Keap1 complex with peptide
 
**[[1x2r]] – mKeap1 Kelch domain + NRF2 Neh2 peptide <br />
**[[2z32]] – mKeap1 Kelch domain + prothymosin a peptide <br />
**[[3ade]], [[3wdz]] – mKeap1 Kelch domain + sequestosome-1 peptide <br />
**[[2dyh]] – mKeap1 Kelch domain + NRF2 residues 22-36 <br />
**[[3wn7]] – mKeap1 Kelch domain + NRF2 residues 17-51 <br />
**[[4ifl]], [[2flu]], [[3zgc]] – hKeap1 Kelch domain + NRF2 Neh2 peptide <br />
 
*Keap1 complex with small molecule
 
**[[3vng]], [[3vnh]] – hKeap1 Kelch domain + oxadiazole derivative <br />
**[[4ifn]] – hKeap1 Kelch domain + quinoline derivative <br />
**[[4l7b]], [[4l7c]], [[4l7d]] [[4n1b]] – hKeap1 Kelch domain (mutant) + quinoline derivative <br />
**[[4in4]] – hKeap1 Kelch domain + inhibitor <br />
**[[4iqk]] – hKeap1 Kelch domain (mutant) + inhibitor <br />
**[[4cxt]] – hKeap1 BTB domain (mutant) + antagonist<br />
 
}}
 
 


== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman
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