FBXL5

The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs.

The protein encoded by this gene belongs to the Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats.

Alternative splicing of this gene generates 2 transcript variants.

The cryo-EM structure of the FBXL5-IRP2 complex revealed an unexpected 2Fe2S cluster embedded in the leucine-rich repeats domain of the F-box protein in close vicinity of the protein-protein interaction interface.

FBXL5 can only engage IRP2 when its 2Fe2S cluster is in the oxidized state, which explains how oxygen tension dictates IRP2 stability.