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43  structures 5  species 0  interactions 11  sequences 1  architecture

Family: Cyclotide (PF03784)

Summary: Cyclotide family

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Cyclotide family Provide feedback

This family contains a set of cyclic peptides with a variety of activities. The structure consists of a distorted triple-stranded beta-sheet and a cysteine-knot arrangement of the disulfide bonds [2]. Cyclotides can be separated into two subfamilies, namely bracelet and moebius. The bracelet cyclotide subfamily tends to contain a larger number of positively charged residues and has a bracelet-like circularisation of the backbone [2]. The moebius cyclotide subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip [2].

Literature references

  1. Daly NL, Koltay A, Gustafson KR, Boyd MR, Casas-Finet JR, Craik DJ; , J Mol Biol 1999;285:333-345.: Solution structure by NMR of circulin A: a macrocyclic knotted peptide having anti-HIV activity. PUBMED:9878410 EPMC:9878410

  2. Craik DJ, Daly NL, Bond T, Waine C; , J Mol Biol 1999;294:1327-1336.: Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. PUBMED:10600388 EPMC:10600388

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005535

Cyclotides (cyclo peptides) are plant peptides of ~30 amino acids with a head to-tail cyclic backbone and six cysteine residues involved in three disulphide bonds. The cyclotides are extremely resistant to proteolysis and are remarkably stable. Cyclotides display a diverse range of biological activities, including uterotonic activity, inhibition of neurotensin binding, hemolytic, anti-HIV and anti-microbial activity. This range of biological activities makes cyclotides amenable to potential pharmaceutical and agricultural applications. Although their precise role in plants has not yet been reported, it appears that they are most likely present as defence molecules [ PUBMED:10600388 , PUBMED:12482862 , PUBMED:12482868 , PUBMED:12946412 ].

The three-dimensional structure of cyclotides is compact and contains a number of beta-turns, three beta strands arranged in a distorted triple-stranded beta-sheet, a short helical segment, and a network of disulphide bonds which form a cystine knot. The cystine knot consists of an embedded ring in the structure, formed by two disulphide bonds and their connecting backbone segments is threaded by a third disulphide bond. Although the cystine knot motif is now well known in a wide variety of proteins, the cyclotides remain as the only example in which a cystine knot is embedded within a circular protein backbone, a motif that is referred to as the cyclic cystine knot (CCK) [ PUBMED:10600388 , PUBMED:12482862 , PUBMED:12482868 , PUBMED:12946412 ].

Cyclotides can be separated into two sub-families, one of which tends to contain a larger number of positively charged residues and has a bracelet-like circularisation of the backbone. The second subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip [ PUBMED:10600388 , PUBMED:12482868 ]. Bracelet and Moebius families of cyclotides possess a Knottin scaffold. The cyclotide family of proteins is abundant in plants from the Rubiaceae and Violaceae families and includes:

  • Kalata B1.
  • Circulins.
  • Cyclopsychotride A.
  • Cycloviolacin O1.

Also included in this entry are cliotides from the leguminous plant Clitoria ternatea. These are cyclotides with known medicinal properties that have antimicrobial activities against Escherichia coli and are cytotoxic to HeLa cells [ PUBMED:21596752 ].

This entry also includes chassatides. There are 18 chassatides peptides: 14 new cyclotides and 4 uncyclotides from the Rubiaceae family. Uncyclotides are the most potent chassatides for antimicrobial, cytotoxic, and hemolytic activities. All uncyclotides belong to the bracelet subfamily, all lacking the Asn/Asp residue at their C termini, which is crucial for backbone cyclization. Genetic characterization of novel cyclotides revealed that their precursors are highly shortened. They consist of five bracelet, two Möbius, and two hybrid cyclotides. Two Met-oxidized derivatives of chassatide C2 and C11 have been isolated, while we know that oxydation of methionine to methionine sulfoxide (MetO) causes a complete loss of biological activities [ PUBMED:22467870 ].

Gene Ontology

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Domain organisation

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Curation and family details

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Seed source: [1]
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A
Number in seed: 30
Number in full: 11
Average length of the domain: 29.50 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 34.65 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.7 25.8
Noise cut-off 19.4 19.8
Model length: 30
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
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 Cyclotide domain has been found. There are 43 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
A0A1D6MXH4 View 3D Structure Click here