Identification of a family of human F-box proteins

Curr Biol. 1999 Oct 21;9(20):1177-9. doi: 10.1016/S0960-9822(00)80020-2.


F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 aminoacid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified) [1]. Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins [2] [3]. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases called SCFs. The other three subunits are the Skp1 protein; one of the cullin proteins (Cul1 in metazoans and Cdc53 or Cul A in the yeast Saccharomyces cerevisiae); and the recently identified Roc1 protein (also called Rbx1 or Hrt1). SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. The need for high substrate specificity and the large number of known F-box proteins in yeast and worms [2] [4] suggest the existence of a large family of mammalian F-box proteins. Using Skp1 as a bait in a yeast two-hybrid screen and by searching DNA databases, we identified a family of 26 human F-box proteins, 25 of which were novel. Some of these proteins contained WD-40 domains or leucine-rich repeats; others contained either different protein-protein interaction modules or no recognizable motifs. We have named the F-box proteins that contain WD-40 domains Fbws, those containing leucine-rich repeats, Fbls, and the remaining ones Fbxs. We have further characterized representative members of these three classes of F-box proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Peptide Synthases / metabolism
  • Proteins / chemistry*
  • Proteins / classification*
  • Proteins / genetics
  • SKP Cullin F-Box Protein Ligases
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Ubiquitins / metabolism


  • Proteins
  • Ubiquitins
  • SKP Cullin F-Box Protein Ligases
  • Peptide Synthases

Associated data

  • GENBANK/AF129530
  • GENBANK/AF129531
  • GENBANK/AF129532
  • GENBANK/AF129533
  • GENBANK/AF129534
  • GENBANK/AF129535
  • GENBANK/AF129536
  • GENBANK/AF129537
  • GENBANK/AF174589
  • GENBANK/AF174590
  • GENBANK/AF174591
  • GENBANK/AF174592
  • GENBANK/AF174593
  • GENBANK/AF174594
  • GENBANK/AF174595
  • GENBANK/AF174596
  • GENBANK/AF174597
  • GENBANK/AF174598
  • GENBANK/AF174599
  • GENBANK/AF174600
  • GENBANK/AF174601
  • GENBANK/AF174602
  • GENBANK/AF174603
  • GENBANK/AF174604
  • GENBANK/AF174605
  • GENBANK/AF174606
  • GENBANK/AF176022