F-box protein 27 (FBXO27)

F-box protein 27 (FBXO27) is a member of the F-box protein family, characterized by the presence of an approximately 40-amino acid F-box motif that mediates interaction with SKP1 in the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex[2][3][4]. As a substrate-recognition component of the SCF complex, FBXO27 recognizes both high-mannose and complex-type N-glycans on denatured or exposed glycoproteins—specifically those normally sequestered in the lumenal surface of lysosomes and other endomembrane structures[1]. Upon lysosomal damage, cytosolic FBXO27 binds to these exposed glycoproteins and promotes their K48-linked ubiquitination, notably targeting proteins such as LAMP2 and VAMP3/7, thereby accelerating the recruitment of autophagy machinery for clearance of damaged organelles (lysophagy)[1]. FBXO27 is unique among glycoprotein-binding F-box proteins in being N-myristoylated, allowing membrane targeting and efficient recruitment to damaged organelles[1]. While general roles for F-box proteins in cancer are recognized (either as tumor suppressors or oncogenes depending on the context), specific roles for FBXO27 in human diseases remain to be fully clarified[5]. No drugs are currently known to interact directly with FBXO27, and it is not yet considered a therapeutic target.

Other names

F-box only protein 27FBG5FBX27Fbg5Fbx27F-box/G-domain protein 5FBXO27F-box protein FBG5epididymis secretory sperm binding protein

Not applicable; no current drugs known to target FBXO27 directly