Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
33  structures 30  species 0  interactions 259  sequences 4  architectures

Family: Cyclotide (PF03784)

Summary: Cyclotide family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Cyclotides". More...

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.

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.

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...

Loading domain graphics...

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(30)
Full
(259)
Representative proteomes NCBI
(274)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
Jalview View  View          View   
HTML View  View             
PP/heatmap 1 View             
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(30)
Full
(259)
Representative proteomes NCBI
(274)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(30)
Full
(259)
Representative proteomes NCBI
(274)
Meta
(0)
RP15
(0)
RP35
(0)
RP55
(0)
RP75
(0)
Raw Stockholm Download   Download           Download    
Gzipped Download   Download           Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

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...

Trees

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.

Note: You can also download the data file for the tree.

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: [1]
Previous IDs: none
Type: Domain
Author: Bateman A
Number in seed: 30
Number in full: 259
Average length of the domain: 29.80 aa
Average identity of full alignment: 57 %
Average coverage of the sequence by the domain: 44.52 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.3 20.3
Trusted cut-off 20.5 20.5
Noise cut-off 17.2 19.8
Model length: 30
Family (HMM) version: 8
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

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 33 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.

Loading structure mapping...