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10  structures 723  species 3  interactions 18379  sequences 524  architectures

Family: F-box (PF00646)

Summary: F-box domain

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This is the Wikipedia entry entitled "F-box protein". More...

F-box protein Edit Wikipedia article

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 138887. PMID 11178263. 

Further reading

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This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

F-box domain Provide feedback

This domain is approximately 50 amino acids long, and is usually found in the N-terminal half of a variety of proteins. Two motifs that are commonly found associated with the F-box domain are the leucine rich repeats (LRRs; PF00560 and PF07723) and the WD repeat (PF00400). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression [3].

Literature references

  1. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ; , Cell 1996;86:263-274.: SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. PUBMED:8706131 EPMC:8706131

  2. Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW; , Cell. 1997;91:209-219.: F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. PUBMED:9346238 EPMC:9346238

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001810

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 [PUBMED:8706131]. 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 [PUBMED:9346238]. 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 [PUBMED:9529603, PUBMED:10581972] or ANK repeats.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan F-box (CL0271), which has the following description:

This clan includes classical F-boxes and the PRANC domain found in pox ankyrin proteins.

The clan contains the following 5 members:

F-box F-box-like F-box-like_2 F-box_4 PRANC


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Curation and family details

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Seed source: Prosite
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 444
Number in full: 18379
Average length of the domain: 45.00 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 10.42 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.5 15.6
Trusted cut-off 20.5 15.6
Noise cut-off 20.4 15.5
Model length: 48
Family (HMM) version: 29
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Species distribution

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There are 3 interactions for this family. More...

Skp1 Skp1 FBA


For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the F-box domain has been found. There are 10 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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