Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2 (, ). The C-terminal domain of FBXL5 contains a redox-sensitive [2Fe-2S] cluster that, upon oxidation, promotes binding to IRP2 to effect its oxygen-dependent degradation . Under iron deficiency conditions, the N-terminal hemerythrin-like (Hr) region, which contains a diiron metal center, cannot bind iron and undergoes conformational changes that destabilize the FBXL5 protein and cause its ubiquitination and degradation (, ). When intracellular iron levels start rising, the Hr region is stabilized (, ). Additional increases in iron levels facilitate the assembly and incorporation of a redox active [2Fe-2S] cluster in the C-terminal domain . Only when oxygen level is high enough to maintain the cluster in its oxidized state can FBXL5 recruit IRP2 as a substrate for polyubiquination and degradation . Promotes ubiquitination and subsequent degradation of the dynactin complex component DCTN1 . Within the nucleus, promotes the ubiquitination of SNAI1; preventing its interaction with DNA and promoting its degradation . Negatively regulates DNA damage response by mediating the ubiquitin-proteasome degradation of the DNA repair protein NABP2 .
Subcellular locations: Cytoplasm, Perinuclear region, Nucleus