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...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Cyclotides Edit Wikipedia article
|Figure 1. Structure and sequence of the prototypic cyclotide kalata B1|
Cyclotides are small disulfide rich peptides isolated from plants. Typically containing 28-37 amino acids, they are characterized by their head-to-tail cyclised peptide backbone and the interlocking arrangement of their three disulfide bonds. These combined features have been termed the cyclic cystine knot (CCK) motif (Figure 1). To date, over 100 cyclotides have been isolated and characterized from species of the Rubiaceae, Violaceae, and Cucurbitaceae families. Cyclotides have also been identified in agriculturally important families such as the Fabaceae and Poaceae.,
 Cyclotide structure
Cyclotides have a well-defined three-dimensional structure as a result of their interlocking disulfide bonds and cyclic peptide backbone. Backbone loops and selected residues are labeled on the structure to help orientation. The amino acid sequence (single letter amino acid representation) for this peptide is indicated on the sequence diagram to the right. One of the interesting features of cyclic peptides is that knowledge of the peptide sequence does not reveal the ancestral head and tail; knowledge of the gene sequence is required for this. In the case of kalata B1 the indicated glycine (G) and asparagine (N) amino acids are the terminal residues that are linked in a peptide bond to cyclise the peptide.
 Biological significance
Cyclotides have been reported to have a wide range of biological activities, including anti-HIV, insecticidal, anti-tumour, antifouling, anti-microbial, hemolytic, neurotensin antagonism, trypsin inhibition, and uterotonic activities. An ability to induce uterine contractions was what prompted the initial discovery of kalata B1.
The potent insecticidal activity of cyclotides kalata B1 and kalata B2 has prompted the belief that cyclotides act as plant host-defence agents (Figure 2). The observations that dozens or more cyclotides may be present in a single plant and the cyclotide architecture comprises a conserved core onto which a series of hypervariable loops is displayed suggest that, cyclotides may be able to target many pests/pathogens simultaneously.
 A Serendipitous Discovery
During a Red Cross relief mission in the Democratic Republic of Congo during the 1960s, a Norwegian doctor, Lorents Gran, noted that during labor African women used a medicinal tea made from the leaves of the plant Oldenlandia affinis (Figure 3) to induce labor and facilitate childbirth. The active ingredient was later determined to be a peptide, named kalata B1, after the traditional name for the native medicine, kalata-kalata. Although in vivo studies in rats confirmed the uterotonic activity of the purified peptide, it was another 20 years before the cyclic cystine knot motif and structure of the purified peptide were elucidated.
 Cyclotide amino-acid sequences
Analysis of the suite of known cyclotides reveals many sequence homologies that are important for understanding their unique physico-chemical properties and bioactivities. Table 1 presents a selection of cyclotides.
The cyclotides fall into two main structural subfamilies. Moebius cyclotides, the less common of the two, contain a cis-proline in loop 5 that induces a local 180° backbone twist (hence likening it to a Möbius strip), whereas bracelet cyclotides do not. There is smaller variation in sequences within these subfamilies than between them. A third subfamily of cyclotides are trypsin inhibitors and are more homologous to a family of non-cyclic trypsin inhibitors from squash plants known as knottins than they are to the other cyclotides.
It is convenient to discuss sequences in terms of the backbone segments, or loops, between successive cysteine residues. The six cysteine residues are absolutely conserved throughout the cyclotide suite and presumably contribute to the preservation of the CCK motif. Although the cysteines appear essential to maintaining the overall fold, several other residues that are highly conserved in cyclotides are thought to provide additional stability.
Throughout the known cyclotides loop 1 is the most conserved. Apart from the six cysteine residues, the glutamic acid and serine/threonine residues of loop 1 are the only residues to have 100% identity across the bracelet and Möbius subfamilies. Furthermore the remaining residue of this loop exhibits only a conservative change i.e. glycine/alanine. This loop is believed to play an important role in stabilizing the cyclotide structure through hydrogen bonding with residues from loops 3 and 5.
Loops 2-6 also have highly conserved features, including the ubiquitous presence of just a single amino acid in loop 4 that is likely involved in sidechain-sidechain hydrogen bonding. Other conserved residues include a hydroxyl-containing residue in loop 3, a glycine residue in the final position of loop 3, a basic and a proline residue in the penultimate position in loop 5 of bracelet and Möbius cyclotides respectively, and an asparagine (or occasionally aspartic acid) residue at the putative cyclisation point in loop 6. It is of interest to note that not only are certain residues highly conserved, but the backbone and side chain angles are as well.
With recent screening programs suggesting that the number of cyclotide sequences may soon reach the thousands, a database, CyBase, has been developed that offers the opportunity for comparisons of sequences and activity data for cyclotides. Several other families of circular proteins are known in bacteria, plants and animals and are also included in CyBase.
 Biosynthesis of cyclotides
Plants are a rich source of cyclic peptides, with the vast majority of these molecules being produced via non-ribosomal biosynthetic pathways. In contrast, the cyclotides are gene-coded products generated via processing of a larger precursor protein. The gene for the first such precursor is Oak1 (Oldenlandia affinis kalata clone number 1), which was shown to be responsible for the synthesis of kalata B1. Figure 4 illustrates the generic configuration of the precursor protein, which consist of an endoplasmic reticulum signal sequence, a non-conserved pro-region, a highly conserved region known as the N-terminal repeat (NTR), the mature cyclotide domain and finally a short hydrophobic C-terminal tail. The cyclotide domain may contain either one cyclotide sequence, as in the case of Oak1, or multiple copies separated by additional NTR sequences as seen for Oak2 and Oak4. In precursor proteins containing multiple cyclotide domains these can either be all identical sequences, as is the case for Oak4, or they can be different cyclotides as in Oak2 which contains sequences corresponding to kalata B3 and B6.
The remarkable stability of cyclotides means that they have an exciting range of potential applications centred on either their intrinsic biological activities or the possibility of using the CCK motif as a scaffold for stabilizing biologically active epitopes. Interest in these has recently intensified with the publications of a chemical methodology capable of synthetically producing cyclotides with high yields, and the amenability of the CCK framework to amino-acid substitutions. But for molecules to be useful in a therapeutic setting they require useful biopharmaceutical characteristics such as resistance to proteolysis and membrane permeability. A recent study on related cystine knot proteins as drug candidates showed that cystine knots do permeate well through rat small intestinal mucosa relative to non-cystine knot peptide drugs such as insulin and bacitracin. Furthermore, enzymatic digestion of cystine knot peptide drugs was associated with only a few proteases and it was suggested that this limitation may be overcome by mutating out particular cleavage sites. Thus, certain cystine knot proteins satisfy the basic criteria for drug delivery and represent exciting novel candidates as scaffolds for peptide drug delivery. The diverse range of intrinsic activities of cyclotides also continues to hold promise for a wide range of applications in the agricultural fields.
a.^ A diet containing 0.8 μmol/g kalata B1 for 16 days significantly hindered development of caterpillar larvae compared with larvae on a diet free of kalata B1. Although no mortality was observed in the first six days for larvae fed the kalata B1 diet, 50% failed to survive past day sixteen. Those that did survive failed to progress pass the first instar stage of development and on average weighed 3.3 mg compared with larvae on the kalata B1 free diet that achieved fifth instar and weighed on average 284 mg 
 See also
- Craik DJ, Daly NL, Bond T, Waine C (1999). "Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif". J. Mol. Biol. 294 (5): 1327–36. doi:10.1006/jmbi.1999.3383. PMID 10600388.
- Poth AG, Colgrave ML, Lyons RE, Daly NL, Craik DJ (2011). "Discovery of an unusual biosynthetic origin for circular proteins in legumes". Proceedings of the National Academy of Sciences 108 (25): 10127–10132. doi:10.1073/pnas.1103660108. PMC 3121837. PMID 21593408. //www.ncbi.nlm.nih.gov/pmc/articles/PMC3121837/.
- Dutton JL, Renda RF, Waine C, et al. (2004). "Conserved structural and sequence elements implicated in the processing of gene-encoded circular proteins". J. Biol. Chem. 279 (45): 46858–67. doi:10.1074/jbc.M407421200. PMID 15328347.
- Craik DJ, Daly NL, Mulvenna J, Plan MR, Trabi M (2004). "Discovery, structure and biological activities of the cyclotides". Curr. Protein Pept. Sci. 5 (5): 297–315. doi:10.2174/1389203043379512. PMID 15544527.
- Göransson U, Sjögren M, Svangård E, Claeson P, Bohlin L (2004). "Reversible antifouling effect of the cyclotide cycloviolacin O2 against barnacles". J. Nat. Prod. 67 (8): 1287–90. doi:10.1021/np0499719. PMID 15332843.
- Gustafson KR, McKee TC, Bokesch HR (2004). "Anti-HIV cyclotides". Curr. Protein Pept. Sci. 5 (5): 331–40. doi:10.2174/1389203043379468. PMID 15544529.
- Gran L (1970). "An oxytocic principle found in Oldenlandia affinis DC An indigenous, Congolese drug kalata-kalataused to accelerate delivery". Medd. Nor. Farm. Selsk 32 (12): 173–80. http://www.popline.org/docs/0103/702847.html.[dead link]
- Voss-Andreae, J (2005). "Protein Sculptures: Life's Building Blocks Inspire Art". Leonardo 38: 41–45. doi:10.1162/leon.2005.38.1.41.
- Gran L, Sandberg F, Sletten K (2000). "Oldenlandia affinis (R&S) DC. A plant containing uteroactive peptides used in African traditional medicine". J Ethnopharmacol 70 (3): 197–203. doi:10.1016/S0378-8741(99)00175-0. PMID 10837983.
- Saether O, Craik DJ, Campbell ID, Sletten K, Juul J, Norman DG (1995). "Elucidation of the primary and three-dimensional structure of the uterotonic polypeptide kalata B1". Biochemistry 34 (13): 4147–58. doi:10.1021/bi00013a002. PMID 7703226.
- Chiche L, Heitz A, Gelly JC, et al. (2004). "Squash inhibitors: from structural motifs to macrocyclic knottins". Curr. Protein Pept. Sci. 5 (5): 341–349. doi:10.2174/1389203043379477. PMID 15551519.
- Rosengren KJ, Daly NL, Plan MR, Waine C, Craik DJ (2003). "Twists, knots, and rings in proteins. Structural definition of the cyclotide framework". J. Biol. Chem. 278 (10): 8606–16. doi:10.1074/jbc.M211147200. PMID 12482868.
- Jennings C, West J, Waine C, Craik D, Anderson M (2001). "Biosynthesis and insecticidal properties of plant cyclotides: The cyclic knotted proteins from Oldenlandia affinis". Proc. Natl. Acad. Sci. U.S.A. 98 (19): 10614–9. doi:10.1073/pnas.191366898. PMC 58514. PMID 11535828. //www.ncbi.nlm.nih.gov/pmc/articles/PMC58514/.
- Ireland DC, Colgrave ML, Nguyencong P, Daly NL, Craik DJ (2006). "Discovery and characterization of a linear cyclotide from Viola odorata: implications for the processing of circular proteins". J. Mol. Biol. 357 (5): 1522–35. doi:10.1016/j.jmb.2006.01.051. PMID 16488428.
- Simonsen SM, Sando L, Ireland DC, et al. (2005). "A Continent of Plant Defense Peptide Diversity: Cyclotides in Australian Hybanthus (Violaceae)". Plant Cell 17 (11): 3176–89. doi:10.1105/tpc.105.034678. PMC 1276036. PMID 16199617. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1276036/.
- Craik DJ (2006). "Chemistry. Seamless proteins tie up their loose ends". Science 311 (5767): 1563–4. doi:10.1126/science.1125248. PMID 16543448.
- Gruber CW, Cemazar M, Anderson MA, Craik DJ (2007). "Insecticidal plant cyclotides and related cystine knot toxins". Toxicon 49 (4): 561–75. doi:10.1016/j.toxicon.2006.11.018. PMID 17224167.
- Craik DJ, Simonsen S, Daly NL (2002). "The cyclotides: novel macrocyclic peptides as scaffolds in drug design". Curr Opin Drug Discov Devel 5 (2): 251–60. PMID 11926131.
- Gunasekera S, Daly NL, Anderson MA, Craik DJ (2006). "Chemical synthesis and biosynthesis of the cyclotide family of circular proteins". IUBMB Life 58 (9): 515–24. doi:10.1080/15216540600889532. PMID 17002979.
- Craik DJ, Cemazar M, Daly NL (2006). "The cyclotides and related macrocyclic peptides as scaffolds in drug design". Curr Opin Drug Discov Devel 9 (2): 251–60. PMID 16566295.
- Werle M, Schmitz T, Huang HL, Wentzel A, Kolmar H, Bernkop-Schnürch A (2006). "The potential of cystine-knot microproteins as novel pharmacophoric scaffolds in oral peptide drug delivery". J Drug Target 14 (3): 137–46. doi:10.1080/10611860600648254. PMID 16753827.
 Further reading
- Shenkarev ZO, Nadezhdin KD, Sobol VA, Sobol AG, Skjeldal L, Arseniev AS (2006). "Conformation and mode of membrane interaction in cyclotides. Spatial structure of kalata B1 bound to a dodecylphosphocholine micelle". FEBS J. 273 (12): 2658–72. doi:10.1111/j.1742-4658.2006.05282.x. PMID 16817894.
- Sancheti H, Camarero JA (September 2009). ""Splicing up" drug discovery. Cell-based expression and screening of genetically-encoded libraries of backbone-cyclized polypeptides". Adv. Drug Deliv. Rev. 61 (11): 908–17. doi:10.1016/j.addr.2009.07.003. PMID 19628015.
- Gerlach SL, Mondal D (2012). "The bountiful biological activities of cyclotides". Chron Young Sci 3: 169–177. http://www.cysonline.org/article.asp?issn=2229-5186;year=2012;volume=3;issue=3;spage=169;epage=177;aulast=Gerlach.
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 . 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 . 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 .
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
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.
- Cyclopsychotride A.
- Cycloviolacin O1.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||defense response (GO:0006952)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
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...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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.
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...
If you find these logos useful in your own work, please consider citing the following article:
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.
|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 build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||8|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
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.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
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.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
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.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
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.
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...