PROSITE documentation PDOC50181
F-box domain profile


First identified in cyclin-F as a protein-protein interaction motif, the F-box is a conserved domain that is present in numerous protein 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 (see <PDOC00574>), leucine rich repeats [3,4] or ANK repeats (see <PDOC50088>).

Some proteins known to contain a F-box are listed below:

  • Mammalian G2/mitotic-specific cyclin-F.
  • Yeast CDC4. It contains WD repeats.
  • Yeast GRR1. It contains a leucine-rich segment.
  • Yeast MET30. It contains WD repeats.
  • Neurospora crassa Scon2. It contains WD repeats.
  • Emericella nidulans SconB. It contains WD repeats.
  • Caenorhabditis elegans sel-10. It contains WD repeats.
  • Xenopus laevis β-TrCP. It contains WD repeats.
  • Poxviruses protein B18. They contain ANK repeats.
Expert(s) to contact by email:

Hofmann K.

Last update:

December 2001 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

FBOX, PS50181; F-box domain profile  (MATRIX)


1AuthorsBai C. Sen P. Hofmann K. Ma L. Goebl M. Harper J.W. Elledge S.J.
TitleSKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box.
SourceCell 86:263-274(1996).
PubMed ID8706131

2AuthorsSkowyra D. Craig K.L. Tyers M. Elledge S.J. Harper J.W.
TitleF-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex.
SourceCell 91:209-219(1997).
PubMed ID9346238

3AuthorsKrek W.
TitleProteolysis and the G1-S transition: the SCF connection.
SourceCurr. Opin. Genet. Dev. 8:36-42(1998).
PubMed ID9529603

4AuthorsCraig K.L. Tyers M.
TitleThe F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction.
SourceProg. Biophys. Mol. Biol. 72:299-328(1999).
PubMed ID10581972

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