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| <StructureSection load='4ifl' size='340' side='right' caption='Human Kelch-like protein19 (Keap1) Kelch domain (dark green) complex with NRF2 Neh2 peptide (light green) (PDB code [[4ifl]])' 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'> |
| '''Kelch-like proteins''' (KLHL) contain multiple Kelch motifs. This motif is about 50 residues long and forms a four-stranded beta-sheet blade. Six to Eight such blades form a circular b-propeller domain. B-prepellers 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.
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| == 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. <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 /> |
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| == Disease == | | == Disease == |
| | Somatic mutations in Keap1 were found in lung cancer patients. |
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| == Relevance == | | == Relevance == |
| | | NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target. |
| '''KLHL19 (Keap1)''' interacts with the Neh2 peptide of NRF2. NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target.
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| == Structural highlights == | | == Structural highlights == |
| | | 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> | |
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| == 3D Structures of Kelch-like protein == | | == 3D Structures of Kelch-like protein == |
| | [[Kelch-like protein 3D structures]] |
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
| | </StructureSection> |
| {{#tree:id=OrganizedByTopic|openlevels=0|
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| *Kelch-like protein 2
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| **[[2xn4]] – hKLHL2 Kelch domain – human <br />
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| *Kelch-like protein 3
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| **[[4chb]], [[4ch9]] – hKLHL3 Kelch domain + serine/threonine protein kinas WNK4 peptide <br />
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| **[[4hxi]] – hKLHL3 BTB-BACK domain (mutant) + cullin-3 N terminal <br />
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| *Kelch-like protein 7
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| **[[3ii7]] – hKLHL7 Kelch domain <br />
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| *Kelch-like protein 11
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| **[[3i3n]] – hKLHL11 BTB-BACK domain <br />
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| **[[4ap2]], [[4apf]] – hKLHL11 BTB-BACK domain + cullin-3 N terminal <br />
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| *Kelch-like protein 12
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| **[[2vpj]] – hKLHL12 Kelch domain <br />
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| *Kelch-like protein 16 (gigaxonin)
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| **[[3hve]] – hKLHL16 <br />
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| **[[2ppi]] – hKLHL16 BTB domain <br />
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| *Kelch-like protein 19 (kelch-like ECH-associated protein 1; Keap1)
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| **[[1u6d]], [[1zgk]], [[4ifj]] – hKeap1 Kelch domain <br />
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| **[[3zgd]] – hKeap1 Kelch domain (mutant) <br />
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| **[[4cxi]], [[4cxj]] – hKeap1 BTB domain (mutant) <br />
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| **[[1x2j]] – mKeap1 Kelch domain - mouse <br />
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| *Keap1 complex with peptide
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| **[[1x2r]] – mKeap1 Kelch domain + NRF2 Neh2 peptide <br />
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| **[[2z32]] – mKeap1 Kelch domain + prothymosin a peptide <br />
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| **[[3ade]], [[3wdz]] – mKeap1 Kelch domain + sequestosome-1 peptide <br />
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| **[[2dyh]] – mKeap1 Kelch domain + NRF2 residues 22-36 <br />
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| **[[3wn7]] – mKeap1 Kelch domain + NRF2 residues 17-51 <br />
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| **[[4ifl]], [[2flu]], [[3zgc]] – hKeap1 Kelch domain + NRF2 Neh2 peptide <br />
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| *Keap1 complex with small molecule
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| **[[3vng]], [[3vnh]] – hKeap1 Kelch domain + oxadiazole derivative <br />
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| **[[4ifn]] – hKeap1 Kelch domain + quinoline derivative <br />
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| **[[4l7b]], [[4l7c]], [[4l7d]] [[4n1b]] – hKeap1 Kelch domain (mutant) + quinoline derivative <br />
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| **[[4in4]] – hKeap1 Kelch domain + inhibitor <br />
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| **[[4iqk]] – hKeap1 Kelch domain (mutant) + inhibitor <br />
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| **[[4cxt]] – hKeap1 BTB domain (mutant) + antagonist<br />
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| }}
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| == References == | | == References == |
| <references/> | | <references/> |
| | [[Category:Topic Page]] |