Summary: Cocaine and amphetamine regulated transcript protein (CART)
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 "Cocaine and amphetamine regulated transcript". 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.
Cocaine and amphetamine regulated transcript Edit Wikipedia article
|Locus||Chr. 5 q13.2|
cocaine- and amphetamine-regulated transcript
Cocaine- and amphetamine-regulated transcript, also known as CART, is a protein that in humans is encoded by the CARTPT gene. CART appears to have roles in reward, feeding, and stress, and it has the functional properties of an endogenous psychostimulant.
CART is a neuropeptide that produces similar behaviour in animals to cocaine and amphetamine, but conversely blocks the effects of cocaine when they are co-administered. The peptide is found in several areas, among them the ventral tegmental area (VTA) of the brain. When CART is injected into rat VTA, increased locomotor activity is seen, which is one of the signs of "central stimulation" caused by substances such as cocaine and amphetamine. The rats also tended to return to the place where they had been injected. This is called conditioned place preference and is seen after injection of cocaine.
CART peptides, in particular, CART (55–102), seem to have an important function in the regulation of energy homeostasis, and interact with several hypothalamic appetite circuits. CART expression is regulated by several peripheral peptide hormones involved in appetite regulation, including leptin, cholecystokinin and ghrelin, with CART and cholecystokinin having synergistic effects on appetite regulation.
CART is released in response to repeated dopamine release in the nucleus accumbens, and may regulate the activity of neurons in this area. CART production is upregulated by CREB, a protein thought to be involved with the development of drug addiction, and CART may be an important therapeutic target in the treatment of stimulant abuse.
CART is an anorectic peptide and is widely expressed in both the central and peripheral nervous systems, particularly concentrated in the hypothalamus. CART is outside of the nervous system also expressed in pituitary endocrine cells, adrenomedullary cells, islet somatostatin cells, and in rat antral gastrin cells. Other structures and pathways associated with CART expression include the mesolimbic pathway (linking the ventral tegmental area to the nucleus accumbens) and amygdala.
CART is also found in a subset of retinal ganglion cells (RGCS), the primary afferent neuron in the retina. Specifically, it has been demonstrated to label ON/OFF Direction Selective Ganglion Cells (ooDSGCs), a subpopulation of RGC that stratify in both the ON and OFF sublamina of the Inner Plexiform Layer (IPL) of the retina. It is also found in a subset of amacrine cells in the Inner Nuclear Layer. No role as of yet has been proposed for the peculiar location of this protein in these cells types.
Studies of CART (54–102) action in rat lateral ventricle and amygdala suggest that CART play a role in anxiety-like behavior, induced by ethanol withdrawal in rats. Studies on CART knock-out mice indicates that CART modulates the locomotor, conditioned place preference and cocaine self-administration effect of psychostimulants. This suggests a positive neuromodulatory action of CART on psychostimulants effect on rat. CART is altered in the ventral tegmental area of cocaine overdose victims, and a mutation in the CART gene associates with alcoholism. CART peptides are inhibitors of food intake (anorexigenic) and closely associated with leptin and neuropeptide Y, two important food intake regulators. CART hypoactivity in the hypothalamus of depressed animals is associated with hyperphagia and weight gain. CART peptides are also involved in fear and startle behavior. CART is thought to play a key role in the opioid mesolimbic dopamine circuit that modulates natural reward processes. CART also appears to play an important role in higher brain functions like cognition.
CART was found by examining changes in the brain following cocaine or amphetamine administration. CART mRNA increased with cocaine administration. One of the goals was to find an endogenous anorexigenic substance. CART inhibited rat food intake by as much as 30 percent. When naturally occurring CART peptides were blocked by means of injecting antibodies to CART, feeding increased. This led to suggestions CART may play a role - though not being the only peptide - in satiety. In the end of the 1980s, researchers started to synthesize cocaine-like and CART-like-acting substances in order to find medications that could affect eating disorders as well as cocaine abuse. These cocaine-like substances are called phenyltropanes.
The putative receptor target for CART has not yet been identified as of 2011, however in vitro studies strongly suggest that CART binds to a specific G protein-coupled receptor coupled to Gi/Go, resulting in increased ERK release inside the cell.
Several fragments of CART have been tested to try and uncover the pharmacophore, but the natural splicing products CART 55–102 and CART 62–102 are still of highest activity, with the reduced activity of smaller fragments thought to indicate that a compact structure retaining all three of CART's disulphide bonds is preferred.
- Douglass J, Daoud S (March 1996). "Characterization of the human cDNA and genomic DNA encoding CART: a cocaine- and amphetamine-regulated transcript". Gene. 169 (2): 241–5. doi:10.1016/0378-1119(96)88651-3. PMID 8647455.
- Kristensen P, Judge ME, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S (May 1998). "Hypothalamic CART is a new anorectic peptide regulated by leptin". Nature. 393 (6680): 72–6. doi:10.1038/29993. PMID 9590691.
- Zhang M, Han L, Xu Y (November 2011). "Roles of cocaine- and amphetamine-regulated transcript in the central nervous system". Clin. Exp. Pharmacol. Physiol. 39 (6): 586–92. doi:10.1111/j.1440-1681.2011.05642.x. PMID 22077697.
- Kuhar MJ, Adams S, Dominguez G, Jaworski J, Balkan B (February 2002). "CART peptides". Neuropeptides. 36 (1): 1–8. doi:10.1054/npep.2002.0887. PMID 12147208.
- Murphy KG (July 2005). "Dissecting the role of cocaine- and amphetamine-regulated transcript (CART) in the control of appetite". Brief Funct Genomic Proteomic. 4 (2): 95–111. doi:10.1093/bfgp/4.2.95. PMID 16102267.
- de Lartigue G, Dimaline R, Varro A, Dockray GJ (March 2007). "Cocaine- and amphetamine-regulated transcript: stimulation of expression in rat vagal afferent neurons by cholecystokinin and suppression by ghrelin". Journal of Neuroscience. 27 (11): 2876–82. doi:10.1523/JNEUROSCI.5508-06.2007. PMID 17360909.
- Maletínská L, Maixnerová J, Matysková R, Haugvicová R, Pirník Z, Kiss A, Zelezná B (2008). "Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice". BMC Neuroscience. 9: 101. doi:10.1186/1471-2202-9-101. PMC . PMID 18939974.
- Hubert GW, Jones DC, Moffett MC, Rogge G, Kuhar MJ (January 2008). "CART peptides as modulators of dopamine and psychostimulants and interactions with the mesolimbic dopaminergic system". Biochemical Pharmacology. 75 (1): 57–62. doi:10.1016/j.bcp.2007.07.028. PMC . PMID 17854774.
- Rogge GA, Jones DC, Green T, Nestler E, Kuhar MJ (January 2009). "Regulation of CART peptide expression by CREB in the rat nucleus accumbens in vivo". Brain Research. 1251: 42–52. doi:10.1016/j.brainres.2008.11.011. PMC . PMID 19046951.
- Fagergren P, Hurd Y (September 2007). "CART mRNA expression in rat monkey and human brain: relevance to cocaine abuse". Physiology & Behavior. 92 (1–2): 218–25. doi:10.1016/j.physbeh.2007.05.027. PMID 17631364.
- Vicentic A, Jones DC (February 2007). "The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction". The Journal of Pharmacology and Experimental Therapeutics. 320 (2): 499–506. doi:10.1124/jpet.105.091512. PMID 16840648.
- Rogge G, Jones D, Hubert GW, Lin Y, Kuhar MJ (October 2008). "CART peptides: regulators of body weight, reward and other functions". Nature Reviews. Neuroscience. 9 (10): 747–58. doi:10.1038/nrn2493. PMC . PMID 18802445.
- Keller PA, Compan V, Bockaert J, Giacobino JP, Charnay Y, Bouras C, Assimacopoulos-Jeannet F (June 2006). "Characterization and localization of cocaine- and amphetamine-regulated transcript (CART) binding sites". Peptides. 27 (6): 1328–34. doi:10.1016/j.peptides.2005.10.016. PMID 16309793.
- Wierup N, Kuhar M, Nilsson BO, Mulder H, Ekblad E, Sundler F (February 2004). "Cocaine- and amphetamine-regulated transcript (CART) is expressed in several islet cell types during rat development". J. Histochem. Cytochem. 52 (2): 169–77. doi:10.1177/002215540405200204. PMID 14729868.
- Dandekar MP, Singru PS, Kokare DM, Lechan RM, Thim L, Clausen JT, Subhedar NK (April 2008). "Importance of cocaine- and amphetamine-regulated transcript peptide in the central nucleus of amygdala in anxiogenic responses induced by ethanol withdrawal". Neuropsychopharmacology. 33 (5): 1127–36. doi:10.1038/sj.npp.1301516. PMID 17637604.
- Couceyro PR, Evans C, McKinzie A, Mitchell D, Dube M, Hagshenas L, White FJ, Douglass J, Richards WG, Bannon AW (December 2005). "Cocaine- and amphetamine-regulated transcript (CART) peptides modulate the locomotor and motivational properties of psychostimulants". J. Pharmacol. Exp. Ther. 315 (3): 1091–100. doi:10.1124/jpet.105.091678. PMID 16099925.
- Kuhar MJ, Jaworski JN, Hubert GW, Philpot KB, Dominguez G (2005). "Cocaine- and amphetamine-regulated transcript peptides play a role in drug abuse and are potential therapeutic targets". AAPS J. 7 (1): E259–65. doi:10.1208/aapsj070125. PMC . PMID 16146347.
- Nakhate KT, Kokare DM, Singru PS, Subhedar NK (June 2011). "Central regulation of feeding behavior during social isolation of rat: evidence for the role of endogenous CART system". Int J Obes (Lond). 35 (6): 773–84. doi:10.1038/ijo.2010.231. PMID 21060312.
- Dandekar MP, Singru PS, Kokare DM, Subhedar NK (April 2009). "Cocaine- and amphetamine-regulated transcript peptide plays a role in the manifestation of depression: social isolation and olfactory bulbectomy models reveal unifying principles". Neuropsychopharmacology. 34 (5): 1288–300. doi:10.1038/npp.2008.201. PMID 19005467.
- "CART (Cocaine- and Amphetamine-Regulated Transcript) Peptides". anaspec.com. Retrieved 10 February 2009.
- Upadhya MA, Nakhate KT, Kokare DM, Singh U, Singru PS, Subhedar NK (March 2012). "CART peptide in the nucleus accumbens shell acts downstream to dopamine and mediates the reward and reinforcement actions of morphine". Neuropharmacology. 62 (4): 1823–33. doi:10.1016/j.neuropharm.2011.12.004. PMID 22186082.
- Bharne AP, Borkar CD, Bodakuntla S, Lahiri M, Subhedar NK, Kokare DM (2016). "Pro-cognitive action of CART is mediated via ERK in the hippocampus". Hippocampus. 26 (10): 1313–27. doi:10.1002/hipo.22608. PMID 27258934.
- "Cocaine Studies Reveal New Medications For Addiction; How Brain Regulates Hunger". ScienceDaily LLC. 27 October 1997. Retrieved 11 February 2009.
- Lin Y, Hall RA, Kuhar MJ (October 2011). "CART peptide stimulation of G protein-mediated signaling in differentiated PC12 cells: identification of PACAP 6-38 as a CART receptor antagonist". Neuropeptides. 45 (5): 351–8. doi:10.1016/j.npep.2011.07.006. PMC . PMID 21855138.
- Lakatos A, Prinster S, Vicentic A, Hall RA, Kuhar MJ (2005). "Cocaine- and amphetamine-regulated transcript (CART) peptide activates the extracellular signal-regulated kinase (ERK) pathway in AtT20 cells via putative G-protein coupled receptors". Neuroscience Letters. 384 (1–2): 198–202. doi:10.1016/j.neulet.2005.04.072. PMID 15908120.
- Vicentic A, Lakatos A, Kuhar MJ (December 2005). "CART (cocaine- and amphetamine-regulated transcript) peptide receptors: specific binding in AtT20 cells". European Journal of Pharmacology. 528 (1–3): 188–9. doi:10.1016/j.ejphar.2005.11.041. PMID 16330022.
- Maletínská L, Maixnerová J, Matysková R, Haugvicová R, Sloncová E, Elbert T, Slaninová J, Zelezná B (March 2007). "Cocaine- and amphetamine-regulated transcript (CART) peptide specific binding in pheochromocytoma cells PC12". European Journal of Pharmacology. 559 (2–3): 109–14. doi:10.1016/j.ejphar.2006.12.014. PMID 17292884.
- Bannon AW, Seda J, Carmouche M, Francis JM, Jarosinski MA, Douglass J (December 2001). "Multiple behavioral effects of cocaine- and amphetamine-regulated transcript (CART) peptides in mice: CART 42-89 and CART 49-89 differ in potency and activity". The Journal of Pharmacology and Experimental Therapeutics. 299 (3): 1021–6. PMID 11714891.
- Dylag T, Kotlinska J, Rafalski P, Pachuta A, Silberring J (August 2006). "The activity of CART peptide fragments". Peptides. 27 (8): 1926–33. doi:10.1016/j.peptides.2005.10.025. PMID 16730858.
- Maixnerová J, Hlavácek J, Blokesová D, Kowalczyk W, Elbert T, Sanda M, Blechová M, Zelezná B, Slaninová J, Maletínská L (October 2007). "Structure-activity relationship of CART (cocaine- and amphetamine-regulated transcript) peptide fragments". Peptides. 28 (10): 1945–53. doi:10.1016/j.peptides.2007.07.022. PMID 17766010.
- cocaine- and amphetamine-regulated transcript protein at the US National Library of Medicine Medical Subject Headings (MeSH)
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.
Cocaine and amphetamine regulated transcript protein (CART) Provide feedback
This family consists of several cocaine and amphetamine regulated transcript type I protein (CART) sequences. Cocaine and amphetamine regulated transcript (CART) peptide has been shown to be an anorectic peptide that inhibits both normal and starvation-induced feeding and completely blocks the feeding response induced by neuropeptide Y and regulated by leptin in the hypothalamus. The C-terminal part containing the three disulfide bridges is the biologically active part of the molecule affecting food intake. The solution structure of the active part of CART has a fold equivalent to other functionally distinct small proteins. CART consists mainly of turns and loops spanned by a compact framework composed by a few small stretches of antiparallel beta-sheet common to cystine knots .
Ludvigsen S, Thim L, Blom AM, Wulff BS; , Biochemistry 2001;40:9082-9088.: Solution structure of the satiety factor, CART, reveals new functionality of a well-known fold. PUBMED:11478874 EPMC:11478874
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR009106
The cocaine and amphetamine regulated transcript (CART) is a brain-localised peptide that acts as a satiety factor in appetite regulation. CART was found to inhibit both normal and starvation-induced feeding, and completely blocks the feeding response induced by neuropeptide Y. CART is regulated by leptin in the hypothalamus, and can be transcriptionally induced after cocaine or amphetamine administration [PUBMED:9590691]. Posttranslational processing of CART produces an N-terminal CART peptide and a C-terminal CART peptide. The C-terminal CART peptide has been isolated from the hypothalamus, nucleus accumbens, and the anterior pituitary lobe in rats. C-terminal CART is the biologically active part of the molecule affecting food intake. The structure of C-terminal CART consists of a disulphide-bound fold containing a beta-hairpin and two adjacent disulphide bridges [PUBMED:11478874].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, 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 UniProtKB sequence database using the family HMM
- 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.
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.
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.
|Seed source:||Pfam-B_15325 (release 9.0)|
|Number in seed:||12|
|Number in full:||88|
|Average length of the domain:||67.50 aa|
|Average identity of full alignment:||69 %|
|Average coverage of the sequence by the domain:||58.78 %|
|HMM build commands:||
build method: hmmbuild --amino -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||9|
|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 CART domain has been found. There are 1 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...