F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions.

It was first identified in cyclin F.[2] The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1.

[4] F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle.

For example, F-box protein-FOA1 involved in abscisic acid (ABA) signaling to affect the seed germination.

[8] In human cells, under high-iron conditions, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.