Kelch-like protein

Function

Kelch-like proteins (KLHL) contain multiple Kelch motifs. This motif is about 50 residues long and forms a four-stranded β-sheet blade. . 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^[1].

• KLHL1 may play a role in organizing the actin cytoskeleton in brain cells.
  
• KLHL2 KLHL11 is a component of the cullin-RING based E3 ubiquitin-protein ligase system.
  
• KLHL3 and KLHL7 KLHL10 are substrate-specific adapters of the cullin-RING based E3 ubiquitin-protein ligase system.
  
• KLHL12 may play a role in collagen export.
  
• KLHL16 or gigaxonin plays a role in neurofilament architecture.
  
• KLHL19 (Keap1) interacts with the Neh2 peptide of NRF2.
  

Disease

Somatic mutations in Keap1 were found in lung cancer patients.

Relevance

NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target.

Structural highlights

The ^[2]. . Water molecules shown as red spheres.