F-box/LRR-repeat protein 5 is a protein that in humans is encoded by the FBXL5gene.[5][6]
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. 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.[6]
FBXL5 is an iron and oxygen sensor. It promotes IRP2 ubiquitination and then its degradation in an iron- and oxygen-dependent manner. The cryo-EM structure of the FBXL5-IRP2 complex was determined by the research group led by Ning Zheng, which 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.[7] FBXL5, therefore, is an iron-sulfur protein. FBXL5 can only engage IRP2 when its 2Fe2S cluster is in the oxidized state, which explains how oxygen tension dictates IRP2 stability.
Ilyin GP, Rialland M, Pigeon C, Guguen-Guillouzo C (2001). "cDNA cloning and expression analysis of new members of the mammalian F-box protein family". Genomics. 67 (1): 40–7. doi:10.1006/geno.2000.6211. PMID10945468.
Zhang N, Liu J, Ding X, Aikhionbare F, Jin C, Yao X (2007). "FBXL5 interacts with p150Glued and regulates its ubiquitination". Biochem. Biophys. Res. Commun. 359 (1): 34–9. doi:10.1016/j.bbrc.2007.05.068. PMID17532294.
