Kelch-like protein
From Proteopedia
(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='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=''> | ||
== 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. 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>.<br /> |
| + | *'''KLHL1''' may play a role in organizing the actin cytoskeleton in brain cells.<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 == | ||
| - | + | NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target. | |
== Structural highlights == | == Structural highlights == | ||
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | ||
{{#tree:id=OrganizedByTopic|openlevels=0| | {{#tree:id=OrganizedByTopic|openlevels=0| | ||
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| + | *Kelch-like protein 1 | ||
| + | |||
| + | **[[4xmb]] – hKLHL1 Kelch domain + NRF2 activator - human <br /> | ||
| + | **[[5cgj]] – mKLHL1 Kelch domain + NRF2 activator - mouse <br /> | ||
*Kelch-like protein 2 | *Kelch-like protein 2 | ||
| - | **[[2xn4]] – hKLHL2 Kelch domain | + | **[[2xn4]] – hKLHL2 Kelch domain <br /> |
*Kelch-like protein 3 | *Kelch-like protein 3 | ||
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**[[4chb]], [[4ch9]] – hKLHL3 Kelch domain + serine/threonine protein kinas WNK4 peptide <br /> | **[[4chb]], [[4ch9]] – hKLHL3 Kelch domain + serine/threonine protein kinas WNK4 peptide <br /> | ||
**[[4hxi]] – hKLHL3 BTB-BACK domain (mutant) + cullin-3 N terminal <br /> | **[[4hxi]] – hKLHL3 BTB-BACK domain (mutant) + cullin-3 N terminal <br /> | ||
| + | |||
| + | *Kelch-like protein 4 | ||
| + | |||
| + | **[[2eqx]] – hKLHL4 BACK domain - NMR <br /> | ||
| + | |||
| + | *Kelch-like protein 5 | ||
| + | |||
| + | **[[4asc]] – hKLHL5 Kelch domain <br /> | ||
*Kelch-like protein 7 | *Kelch-like protein 7 | ||
**[[3ii7]] – hKLHL7 Kelch domain <br /> | **[[3ii7]] – hKLHL7 Kelch domain <br /> | ||
| + | |||
| + | *Kelch-like protein 10 | ||
| + | |||
| + | **[[2woz]] – KLHL10 Kelch domain - rat <br /> | ||
*Kelch-like protein 11 | *Kelch-like protein 11 | ||
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**[[3zgd]] – hKeap1 Kelch domain (mutant) <br /> | **[[3zgd]] – hKeap1 Kelch domain (mutant) <br /> | ||
**[[4cxi]], [[4cxj]] – hKeap1 BTB domain (mutant) <br /> | **[[4cxi]], [[4cxj]] – hKeap1 BTB domain (mutant) <br /> | ||
| - | **[[1x2j]] – mKeap1 Kelch domain | + | **[[1x2j]] – mKeap1 Kelch domain <br /> |
*Keap1 complex with peptide | *Keap1 complex with peptide | ||
Revision as of 06:57, 6 April 2016
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3D Structures of Kelch-like protein
Updated on 06-April-2016
References
- ↑ Dhanoa BS, Cogliati T, Satish AG, Bruford EA, Friedman JS. Update on the Kelch-like (KLHL) gene family. Hum Genomics. 2013 May 15;7:13. doi: 10.1186/1479-7364-7-13. PMID:23676014 doi:http://dx.doi.org/10.1186/1479-7364-7-13
- ↑ Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S, Yamamoto M. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell. 2006 Mar 3;21(5):689-700. PMID:16507366 doi:10.1016/j.molcel.2006.01.013
