Article · Wikipedia archive · Last revised Jun 16, 2026

F-box protein

F-box proteins, sometimes abbreviated as FBX, 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 26S proteasome.

Last revised
Jun 16, 2026
Read time
≈ 3 min
Length
719 w
Citations
12
Source
Wikipedia ↗
F-box linker domain
Structure of the LRR linker domain of Skp2 in the Skp1-Skp2 complex.1
Identifiers
SymbolF-box
PfamPF00646
Pfam clanCL0271
InterProIPR001810
SMARTSM00256
PROSITEPS50181
SCOP21fs2 / SCOPe / SUPFAM
Membranome630
Available protein structures:
PDB  IPR001810 PF00646 (ECOD; PDBsum)  
AlphaFold

F-box proteins, sometimes abbreviated as FBX,23 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 26S proteasome.

Core components

F-box domain is a protein structural motif of about 50 amino acids that mediates protein–protein interactions. It has consensus sequence and varies in few positions. It was first identified in cyclin F.4 The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1.4 F-box domains commonly exist in proteins in cancer with other protein–protein interaction motifs such as leucine-rich repeats (illustrated in the Figure) and WD repeats, which are thought to mediate interactions with SCF substrates.5

Function

F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle.6 In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference.7 F-box proteins are involved in many plant vegetative and reproduction growth and development. For example, F-box protein-FOA1 involved in abscisic acid (ABA) signaling to affect the seed germination.8 ACRE189/ACIF1 can regulate cell death and defense when the pathogen is recognized in the Tobacco and Tomato plant.9

In human cells, under high-iron conditions, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.10

Regulation

F-box protein levels can be regulated by different mechanisms. The regulation can occur via protein degradation process and association with SCF complex . For example, in yeast, the F-box protein Met30 can be ubiquitinated in a cullin-dependent manner.11

References

References

  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. Bibcode:2000Natur.408..381S. doi:10.1038/35042620. PMID 11099048. S2CID 4300503.
  2. Hua Z, Zou C, Shiu SH, Vierstra RD (28 January 2011). "Phylogenetic Comparison of F-Box (FBX) Gene Superfamily within the Plant Kingdom Reveals Divergent Evolutionary Histories Indicative of Genomic Drift". PLOS ONE. 6 (1) e16219. Bibcode:2011PLoSO...616219H. doi:10.1371/journal.pone.0016219. ISSN 1932-6203. PMC 3030570. PMID 21297981.
  3. Kuroda H, Yanagawa Y, Takahashi N, Horii Y, Matsui M (15 November 2012). "A Comprehensive Analysis of Interaction and Localization of Arabidopsis SKP1-LIKE (ASK) and F-Box (FBX) Proteins". PLOS ONE. 7 (11) e50009. Bibcode:2012PLoSO...750009K. doi:10.1371/journal.pone.0050009. ISSN 1932-6203. PMC 3499479. PMID 23166809.
  4. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, et al. (1996). "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box". Cell. 86 (2): 263–274. 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 138887. PMID 11178263.
  6. 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.
  7. Jones-Rhoades MW, Bartel DP, Bartel B (2006). "MicroRNAS and their regulatory roles in plants". Annu Rev Plant Biol. 57 (1): 19–53. Bibcode:2006AnRPB..57...19J. doi:10.1146/annurev.arplant.57.032905.105218. PMID 16669754.
  8. Peng J, Yu D, Wang L, Xie M, Yuan C, Wang Y, et al. (2012). "Arabidopsis F-box gene FOA1 involved in ABA signaling". Science China Life Sciences. 55 (6): 497–506. doi:10.1007/s11427-012-4332-9. PMID 22744179.
  9. Ha VD, Tsitsigiannis DI, Rowland O, Lo J, Rallapalli G, Maclean D, et al. (2008). "The F-box protein ACRE189/ACIF1 regulates cell death and defense responses activated during pathogen recognition in tobacco and tomato". Plant Cell. 20 (3): 697–719. Bibcode:2008PlanC..20..697V. doi:10.1105/tpc.107.056978. PMC 2329923. PMID 18375657.
  10. Moroishi T, Nishiyama M, Takeda Y, Iwai K, Nakayama KI (2011). "The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo". Cell Metabolism. 14 (3): 339–351. doi:10.1016/j.cmet.2011.07.011. PMID 21907140.
  11. Kaiser P, Su NY, Yen JL, Ouni I, Flick K (2006). "The yeast ubiquitin ligase SCFMet30: connecting environmental and intracellular conditions to cell division". Cell Division. 1: 16. doi:10.1186/1747-1028-1-16. PMC 1579207. PMID 16895602.
Further reading

Further reading

External links