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Beschreibung

F-box only protein 15 (UniProt Q8NCQ5) is encoded by the FBXO15 (also known as FBX15) gene (Gene ID 201456) in human. Polyubiquitination of proteins is mediated by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). There exist RING finger-type, HECT-type, U-box-type, and PHD-finger-type E3 ligases. The RING finger-type E3s include seven cullin-based E3s, such as SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C). F-box proteins use their N-terminal F-box motif to bind Skp1 and other motif(s) in their C-terminal region for substrates recognition and recruitment. F-box proteins are divided into the FBXW subclass that contains WD40 repeat domains, the FBXL subclass that contains leucine-rich repeat domains, and the F-box only (FBXO) subclass that contains not yet fully characterized substrate recognition domains. SCF-Fbxo15 is reported to mediate the ubiquitination of cardiolipin synthase (CLS1) for proteasomal degradation in human lung epithelial cells. PTEN-induced putative kinase 1 (PINK1) is shown to phosphorylate CLS1 and cause its release from the inner mitochondrial membrane to the outer membrane, making it accessible for Fbxo15-targeted ubiquitination.