F-box protein

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F-box domain
PDB 1fs2 EBI.jpg
Structure of the Skp1-Skp2 complex.[1]
Symbol F-box
Pfam PF00646
Pfam clan CL0271
InterPro IPR001810
SCOP 1fs2

F-box proteins are proteins containing at least one F-box domain. The first identified F-box protein is one of three components of the SCF complex, which mediates ubiquitination of proteins targeted for degradation by the proteasome. F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle.[2] In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference.[3] In human cells, in high-iron condition, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.[citation needed]

The 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. The F-box motif interacts directly with the SCF protein Skp1,[4] and F-box domains commonly exist in proteins in concert with other protein–protein interaction motifs such as leucine-rich repeats and WD repeats, which are thought to mediate interactions with SCF substrates.[5]


  1. ^ Schulman BA, Carrano AC, Jeffrey PD, et al. (November 2000). "Insights into SCF ubiquitin ligases from the structure of the Skp1-Skp2 complex". Nature. 408 (6810): 381–6. doi:10.1038/35042620. PMID 11099048. 
  2. ^ Craig KL, Tyers M (1999). "The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction". Prog. Biophys. Mol. Biol. 72 (3): 299–328. doi:10.1016/S0079-6107(99)00010-3. PMID 10581972. 
  3. ^ Jones-Rhoades MW, Bartel DP, Bartel B (2006). "MicroRNAS and their regulatory roles in plants". Annu Rev Plant Biol. 57: 19–53. doi:10.1146/annurev.arplant.57.032905.105218. PMID 16669754. 
  4. ^ Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ (July 1996). "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box". Cell. 86 (2): 263–74. doi:10.1016/S0092-8674(00)80098-7. PMID 8706131. 
  5. ^ Kipreos ET, Pagano M (2000). "The F-box protein family". Genome Biol. 1 (5): REVIEWS3002. doi:10.1186/gb-2000-1-5-reviews3002. PMC 138887Freely accessible. PMID 11178263. 

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