Summary: F-box domain
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F-box protein Edit Wikipedia article
|F-box linker domain|
Structure of the LRR linker domain of Skp2 in the Skp1-Skp2 complex.
|SCOPe||1fs2 / SUPFAM|
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.
F-box domain is a protein structural motif of about 50 amino acids that mediates proteinâ€“protein interactions. It has consensus sequence and varies in few positions. It was first identified in cyclin F. The F-box motif of Skp2, consisting of three alpha-helices, interacts directly with the SCF protein Skp1. F-box domains commonly exist in proteins in concert with other proteinâ€“protein interaction motifs such as leucine-rich repeats (illustrated in the Figure) and WD repeats, which are thought to mediate interactions with SCF substrates.
F-box proteins have also been associated with cellular functions such as signal transduction and regulation of the cell cycle. In plants, many F-box proteins are represented in gene networks broadly regulated by microRNA-mediated gene silencing via RNA interference. 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. ACRE189/ACIF1 can regulate cell death and defense when the pathogen is recognized in the Tobacco and Tomato plant.
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.
- 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): 381â€“6. doi:10.1038/35042620. PMID 11099048.
- 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.
- 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): 263â€“74. doi:10.1016/S0092-8674(00)80098-7. PMID 8706131.
- 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.
- 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): 299â€“328. doi:10.1016/S0079-6107(99)00010-3. PMID 10581972.
- Jones-Rhoades MW, Bartel DP, Bartel B (2006). "MicroRNAS and their regulatory roles in plants". Annu Rev Plant Biol. 57: 19â€“53. doi:10.1146/annurev.arplant.57.032905.105218. PMID 16669754.
- 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): 497â€“506. doi:10.1007/s11427-012-4332-9. ISSN 1869-1889. PMID 22744179.
- 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.
- 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.
- 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.
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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].
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
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
|SCOOP:||Beta-TrCP_D Elongin_A F-box-like F-box_4 F-box_5|
|Similarity to PfamA using HHSearch:||F-box-like F-box_4 F-box_5|
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.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||protein binding (GO:0005515)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Key: available, not generated, — not available.
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|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 build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||36|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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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.