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19  structures 1545  species 0  interactions 65401  sequences 1466  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 linker domain
PDB 1fs2 EBI.jpg
Structure of the LRR linker domain of Skp2 in the Skp1-Skp2 complex.[1]
Pfam clanCL0271

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 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.[2] The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1.[3] F-box domains commonly exist in proteins in concert 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.[4]


F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle.[5] In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference.[6] 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.[7] ACRE189/ACIF1 can regulate cell death and defense when the pathogen is recognized in the Tobacco and Tomato plant.[8]

In human cells, under high-iron conditions, two iron atoms stabilise the F-Box FBXL5 and then the complex mediates the ubiquitination of IRP2.[9]


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.[10][11]


  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. ^ Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ. "SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box". Cell 86 263-74 1996.
  3. ^ 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.
  4. ^ 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.
  5. ^ 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.
  6. ^ 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.
  7. ^ Peng, Juan; Yu, Dashi; Wang, Liqun; Xie, Minmin; Yuan, Congying; Wang, Yu; Tang, Dongying; Zhao, Xiaoying; Liu, Xuanming (June 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. ISSN 1869-1889. PMID 22744179.
  8. ^ Ha, Van Den Burg; Tsitsigiannis, D. I.; Rowland, O; Lo, J; Rallapalli, G; Maclean, D; Takken, F. L.; Jones, J. D. (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.
  9. ^ Moroishi, T; Nishiyama, M; Takeda, Y; Iwai, K; Nakayama, K. I. (2011). "The FBXL5-IRP2 axis is integral to control of iron metabolism in vivo". Cell Metabolism. 14 (3): 339.
  10. ^ Kaiser, Peter; Su, Ning-Yuan; Yen, James L.; Ouni, Ikram; Flick, Karin (2006-08-08). "The yeast ubiquitin ligase SCFMet30: connecting environmental and intracellular conditions to cell division". Cell Division. 1: 16. doi:10.1186/1747-1028-1-16. ISSN 1747-1028.

Further reading

External links

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 [1-2].

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

Internal database links

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 proteins 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 7 members:

Elongin_A F-box F-box-like F-box-like_2 F-box_4 F-box_5 PRANC


We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 426
Number in full: 65401
Average length of the domain: 41.80 aa
Average identity of full alignment: 23 %
Average coverage of the sequence by the domain: 9.13 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -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: 43
Family (HMM) version: 36
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence


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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 19 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A096QN59 View 3D Structure Click here
A0A096S4N1 View 3D Structure Click here
A0A096UDW3 View 3D Structure Click here
A0A0G2JVR2 View 3D Structure Click here
A0A0G2KB30 View 3D Structure Click here
A0A0N7KEM4 View 3D Structure Click here
A0A0N7KFI1 View 3D Structure Click here
A0A0N7KFZ4 View 3D Structure Click here
A0A0N7KHR2 View 3D Structure Click here
A0A0N7KJL2 View 3D Structure Click here
A0A0N7KK85 View 3D Structure Click here
A0A0N7KNS1 View 3D Structure Click here
A0A0N7KPK9 View 3D Structure Click here
A0A0N7KQ68 View 3D Structure Click here
A0A0N7KQ92 View 3D Structure Click here
A0A0N7KRD9 View 3D Structure Click here
A0A0N7KT42 View 3D Structure Click here
A0A0N7KU47 View 3D Structure Click here
A0A0P0V7U0 View 3D Structure Click here
A0A0P0VEH0 View 3D Structure Click here
A0A0P0VFJ1 View 3D Structure Click here
A0A0P0VFW1 View 3D Structure Click here
A0A0P0VGE5 View 3D Structure Click here
A0A0P0VJA1 View 3D Structure Click here
A0A0P0VJA5 View 3D Structure Click here
A0A0P0VMA4 View 3D Structure Click here
A0A0P0VRF3 View 3D Structure Click here
A0A0P0VRG8 View 3D Structure Click here
A0A0P0VRI1 View 3D Structure Click here
A0A0P0VRN2 View 3D Structure Click here
A0A0P0VRP6 View 3D Structure Click here
A0A0P0VUW0 View 3D Structure Click here
A0A0P0VXS8 View 3D Structure Click here
A0A0P0VYS8 View 3D Structure Click here
A0A0P0VZH9 View 3D Structure Click here
A0A0P0VZY5 View 3D Structure Click here
A0A0P0VZY9 View 3D Structure Click here
A0A0P0W0W5 View 3D Structure Click here
A0A0P0W160 View 3D Structure Click here
A0A0P0W1I3 View 3D Structure Click here