InterPro domain: IPR036047

First identified in cyclin-F as a protein-protein interaction motif, the F-boxis a conserved domain that is present in numerous proteins with a bipartite structure [ 1 ]. Through the F-box, these proteins are linked to the Skp1 protein and the core of SCFs (Skp1-cullin-F-box protein ligase) complexes. SCFs complexes constitute a new class of E3 ligases [ 2 ]. They function in combination with the E2 enzyme Cdc34 to ubiquitinate G1 cyclins, Cdk inhibitors and many other proteins, to mark them for degradation. The binding of the specific substrates by SCFs complexes is mediated by divergent protein-protein interaction motifs present in F-box proteins, like WD40 repeats, leucine rich repeats [ 3 , 4 ] or ANK repeats.

1. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86, 263-74
2. F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell 91, 209-19
3. Proteolysis and the G1-S transition: the SCF connection. Curr. Opin. Genet. Dev. 8, 36-42
4. The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction. Prog. Biophys. Mol. Biol. 72, 299-328