Summary: Acetoacetate decarboxylase (ADC)
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 "Acetoacetate decarboxylase". 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.
Acetoacetate decarboxylase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
Acetoacetate decarboxylase (AAD or ADC) is an enzyme involved in both the ketone body production pathway in humans and other mammals, and solventogenesis in bacteria. Acetoacetate decarboxylase plays a key role in solvent production by catalyzing the decarboxylation of acetoacetate, yielding acetone and carbon dioxide. This enzyme has been of particular interest because it is a classic example of how pKa values of ionizable groups in the enzyme active site can be significantly perturbed. Specifically, the pKa value of lysine 115 in the active site is unusually low, allowing for the formation of a Schiff base intermediate and catalysis.
|acetoacetic acid||Acetoacetate decarboxylase||acetone|
Acetoacetate decarboxylase is an enzyme with major historical implications, specifically in World War I and in establishing the state of Israel. During the war the Allies needed pure acetone as a solvent for nitro-cellulose, a highly flammable compound that is the main component in gunpowder. In 1916, biochemist and future first president of Israel Chaim Weizmann was the first to isolate Clostridium acetobutylicum, a Gram-positive, anaerobic bacteria in which acetoacetate decarboxylase is found. Weizmann was able to harness the organism’s ability to yield acetone from starch in order to mass-produce explosives during the war. This led the American and British governments to install the process devised by Chaim Weizmann in several large plants in England, France, Canada, and the United States. Through Weizmann’s scientific contributions in World War I, he became close with influential British leaders educating them of his Zionist beliefs. One of them was Arthur Balfour, the man after whom the Balfour Declaration—the first document pronouncing British support in the establishment of a Jewish homeland—was named.
The production of acetone by acetoacetate decarboxylase-containing or clostridial bacteria was utilized in large-scale industrial syntheses in the first half of the twentieth century. In the 1960s, the industry replaced this process with less expensive, more efficient chemical syntheses of acetone from petroleum and petroleum derivatives. However, there has been a growing interest in acetone production that is more environmentally friendly, causing a resurgence in utilizing acetoacetate decarboxylase-containing bacteria. Similarly, isopropanol and butanol fermentation using clostridial species is also becoming popular.
Acetoacetate decarboxylase is a 365 kDa complex with a homododecameric structure. The overall structure consists of antiparallel β-sheets and a central seven-stranded cone-shaped β-barrel. The core of this β-barrel surrounds the active site in each protomer of the enzyme. The active site, consisting of residues such as Phe27, Met97, and Tyr113, is mostly hydrophobic. However, the active site does contain two charged residues: Arg29 and Glu76. Arg29 is thought to play a role in substrate binding, while Glu76 is thought to play a role in the orienting the active site for catalysis. The overall hydrophobic environment of the active site plays a critical role in favoring the neutral amine form of Lys115, a key residue involved in the formation of a Schiff base intermediate. Another important lysine residue, Lys116, is thought to play an important role in the positioning of Lys115 in the active site. Through hydrogen bonds with Ser16 and Met210, Lys116 positions Lys115 in the hydrophobic pocket of the active site to favor the neutral amine form.
Acetoacetate decarboxylase from Clostridium acetobutylicum catalyzes the decarboxylation of acetoacetate to yield acetone and carbon dioxide (Figure 1). The reaction mechanism proceeds via the formation of a Schiff base intermediate, which is covalently attached to lysine 115 in the active site. The first line of support for this mechanism came from a radiolabeling experiment in which researchers labeled the carbonyl group of acetoacetate with 18O and observed that oxygen exchange to water, used as the solvent, is a necessary part of decarboxylation step. These results provided support that the mechanism proceeds through a Schiff base intermediate between the ketoacid and an amino acid residue on the enzyme.
Further research led to the isolation of an active site peptide sequence and identification of the active site lysine, Lys115, that is involved in the formation of the Schiff base intermediate. Additionally, later experiments led to the finding that maximum activity of the enzyme occurs at pH 5.95, suggesting that the pKa of the ε-ammonium group of Lys115 is significantly perturbed in the active site. If the pKa were not perturbed downward, the lysine residue would remain protonated as an ammonium cation, making it unreactive for the nucleophilic addition necessary to form the Schiff base.
Building upon this finding, Westheimer et al. directly measured the pKa of Lys115 in the active site using 5-nitrosalicylaldehyde (5-NSA) . Reaction of 5-NSA with acetoacetate decarboxylase and subsequent reduction of the resulting Schiff base with sodium borohydride led to the incorporation of a 2-hydroxy-5-nitrobenzylamino reporter molecule in the active site (Figure 2). Titration of the enzyme with this attached reporter group revealed that the pKa of Lys115 is decreased to 5.9 in the active site. These results were the basis for the proposal that the perturbation in the pKa of Lys115 was due to its proximity to the positively charged ε-ammonium group of Lys116 in the active site. A nearby positive charge could cause unfavorable electrostatic repulsions that weaken the N-H bond of Lys115. Westheimer et al.'s proposal was further supported by site-directed mutagenesis studies. When Lys116 was mutated to cysteine or asparagine, the pKa of Lys115 was found to be significantly elevated to over 9.2, indicating that positively charged Lys116 plays a critical role in determining the pKa of Lys115. Although a crystal structure was not yet solved to provide structural evidence, this proposal was widely accepted and cited as a textbook example of how the active site can be precisely organized to perturb a pKa and affect reactivity.
In 2009, a crystal structure of acetoacetate decarboxylase from Clostridium acetobutylicum was solved, allowing Westheimer et al.'s proposal to be evaluated from a new perspective . From the crystal structure, researchers found that Lys 115 and Lys 116 are oriented in opposite directions and separated by 14.8 Å (Figure 3). This distance makes it unlikely that the positive charge of Lys116 is able to affect the pKa of Lys115. Instead through hydrogen bonds with Ser16 and Met210, Lys116 likely holds Lys115 into position in a hydrophobic pocket of the active site. This positioning disrupts the stability of the protonated ammonium cation of Lys115, suggesting that the perturbation of Lys115's pKa occurs through a 'desolvation effect'.
Inactivation and inhibition
Acetoacetate decarboxylase is inhibited by a number of compounds. Acetic anhydride performs a nucleophilic attack on the critical catalytic residue, Lys115, of acetoacetate decarboxylase to inactivate the enzyme. The rate of inactivation was assessed through the hydrolysis of the synthetic substrate 2,4-dinitrophenyl propionate to dinitrophenol by acetoacetate decarboxylase. In the presence of acetic anhydride, the enzyme is inactivated, unable to catalyze the hydrolysis reaction 2,4-dinitrophenyl propionate to dinitrophenol.
Acetonylsulfonate acts as a competitive inhibitor (KI=8.0 mM ) as it mimics the characteristics of the natural substrate, acetoacetate (KM=8.0 mM). The monoanion version of acetonylphosphonate is also a good inhibitor (KI=0.8mM), more efficient than the acetonylphosphonate monoester or dianion. These findings indicate that active site is very discriminatory and sterically restricted.
Hydrogen cyanide seems to be an uncompetitive inhibitor, combining with Schiff’s base compounds formed at the active site. Addition of carbonyl compounds to the enzyme, in the presence of hydrogen cyanide, increases hydrogen cyanide’s ability to inhibit acetoacetate decarboxylase suggesting that carbonyl compounds readily form Schiff’s bases at the active site. Hydrogen cyanide is most potent as an inhibitor at pH 6, the optimum pH for the enzyme, suggesting that the rate-limiting step of catalysis is the formation of the Schiff base intermediate.
Beta-diketones appear to inhibit acetoacetate decarboxylase well but slowly. Acetoacetate decarboxylase has a KM for acetoacetate of 7x10−3 M whereas the enzyme has a KI for benzoylacetone of 1.9x10−6 M. An enamine is most likely formed upon interaction of beta-diketones with free enzyme.
The reaction of acetoacetate decarboxylase with p-chloromercuriphenylsulfonate (CMS) results in decreased catalytic activity upon two equivalents of CMS per enzyme subunit. CMS interacts with two sulfhydryl groups located on each enzyme subunit. Further inactivation occurs upon addition of a third equivalent of CMS per subunit. Addition of free cysteine to the inhibited enzyme is able to reverse CMS inhibition of acetoacetate decarboxylase.
Activity in bacteria
Acetoacetate decarboxylase has been found and studied in the following bacteria in addition to Clostridium acetobutylicum:
- Bacillus polymyxa
- Chromobacterium violaceum
- Clostridium beijerinckii
- Clostridium cellulolyticum
- Pseudomonas putida
Activity in humans and mammals
In humans and other mammals, the conversion of acetoacetate into acetone and carbon dioxide by acetoacetate decarboxylase is a final irreversible step in the ketone-body pathway that supplies the body with a secondary source of energy. In the liver, acetyl co-A formed from fats and lipids are transformed into three ketone bodies: acetone, acetoacetate, and D-β-hydroxybutyrate. Acetoacetate and D-β-hydroxybutyrate are exported to non-hepatic tissues, where they are converted back into acetyl-coA and used for fuel. Acetone and carbon dioxide on the other hand are exhaled, and not allowed to accumulate under normal conditions.
Acetoacetate and D-β-hydroxybutyrate freely interconvert through the action of D-β-hydroxybutyrate dehydrogenase. Subsequently, one function of acetoacetate decarboxylase may be to regulate the concentrations of the other, two 4-carbon ketone bodies.
Ketone body production increases significantly when the rate of glucose metabolism is insufficient in meeting the body's energy needs. Such conditions include high-fat ketogenic diets, diabetic ketoacidosis, or severe starvation.
Under elevated levels of acetoacetate and D-β-hydroxybutyrate, acetoacetate decarboxylase produces significantly more acetone. Acetone is toxic, and can accumulate in the body under these conditions. Elevated levels of acetone in the human breath can be used to diagnose diabetes.
- Peterson DJ, Bennett GN (1990). "Purification of acetoacetate decarboxylase from Clostridium acetobutylicum ATCC cloning of the acetoacetate decarboxylase in Escherichia coli.". Applied and Environmental Microbiology 56 (11): 3491–3498.
- Highbarger, LA; JA Gerlt; GL Kenyon (January 9, 1996). "Mechanism of the reaction catalyzed by acetoacetate decarboxylase. Importance of lysine 116 in determining the pKa of active site lysine 115". Biochemistry 9 (35): 41–46. doi:10.1021/bi9518306. PMID 8555196.
- Bormon, S (2009). "New Structure Revisits History". Structural Biology 87 (21): 9.
- "Britannica Online".
- "Jewish Virtual Library".
- "Modeling of ABE Fermentation".
- Collas, Florent; Wouter Kuit; Benjamin Clement; Remy Marchal; Ana M Lopez-Contreras; Frederic Monot (August 21, 2012). "Simultaneous production of isoproponal, butanol, ethanol, and 2,3-butanediol by Clostridium acetobutylicum ATCC 824 engineered strains". AMB Express 2 (1): 45. doi:10.1186/2191-0855-2-45. PMC 3583297. PMID 22909015.
- Ho, Meng-Chiao; Jean-Francois Menetret, Hiro Tsuruta, Karen N. Allen (May 21, 2009). "The origin of the electrostatic pertubation in acetoacetate decarboxylase". Nature 459: 393–397. doi:10.1038/nature07938.
- Hamilton GA, Westheimer FH (1959). "On the Mechanism of Enzymatic Decarboxylation of Acetoacetate". J. Am. Chem. Soc. 81 (23): 6332–6333. doi:10.1021/ja01532a058.
- Warren, Stuart; Burt Zerner, F.H. Westheimer (March 1966). "Acetoacetate Decarboxylase. Identification of Lysine at the Active Site.". Biochemistry 5 (3): 817–823. doi:10.1021/bi00867a002.
- "A History of Acetoacetate Decarboxylase". JinKai.org. Retrieved 26 May 2014.
- Kokesh, Fritz C.; F.H. Westheimer (December 29, 1971). "A reporter group at the active site of acetoacetate decarboxylase. Ionization constant of the amino group.". Journal of the American Chemical Society 93 (26): 7270–7274. doi:10.1021/ja00755a025.
- O'Leary, M.H.; F.H. Westheimer (1968). "Acetoacetate decarboxylase. Selective acetylation of enzyme". Biochemistry 7 (3): 913–919. doi:10.1021/bi00843a005.
- Schmidt, Donald E.; F.H. Westheimer (1971). "pK of the Lysine Amino Group at the Active Site of Acetoacetate Decarboxylase". Biochemistry 10 (7): 1249–1253. doi:10.1021/bi00783a023.
- Autor, Anne P.; I. Fridovich (1970). "The Interactions of Acetoacetate Decarboxylase with Carbonyl Compounds, Hydrogen Cyanide, and an Organic Mercurial". J. Biol. Chem. 245 (20): 5214–5222.
- Kluger, Ronald; Kurt Nakaoka (1974). "Inhibition of Acetoacetate Decarboxylase by Ketophosphonates. Structural and Dyanmic Probes of the Active Site". Biochemistry 13 (5): 910–914. doi:10.1021/bi00702a013.
- van Stekelenburg GJ, Koorevaar G (June 1972). "Evidence for the existence of mammalian acetoacetate decarboxylase: with special reference to human blood serum". Clin. Chim. Acta 39 (1): 191–9. doi:10.1016/0009-8981(72)90316-6. PMID 4624981.
- Koorevaar G, Van Stekelenburg GJ (September 1976). "Mammalian acetoacetate decarboxylase activity. Its distribution in subfractions of human albumin and occurrence in various tissues of the rat". Clin. Chim. Acta 71 (2): 173–83. doi:10.1016/0009-8981(76)90528-3. PMID 963888.
- "Human Metabolism".
- Galassetti PR, Novak B, Nemet D, Rose-Gottron C, Cooper DM, Meinardi S, Newcomb R, Zaldivar F, Blake DR (2005). "Breath ethanol and acetone as indicators of serum glucose levels: an initial report". Diabetes Technol. Ther. 7 (1): 115–23. doi:10.1089/dia.2005.7.115. PMID 15738709.
- acetoacetate decarboxylase at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 22.214.171.124
- Brenda: Entry of Acetoacetate decarboxylase
- KEGG: Entry of Acetoacetate decarboxylase
- InterPro: IPR010451 Acetoacetate decarboxylase
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.
Acetoacetate decarboxylase (ADC) Provide feedback
This family consists of several acetoacetate decarboxylase (ADC) proteins ( EC:126.96.36.199).
Gerischer U, Durre P; , J Bacteriol 1990;172:6907-6918.: Cloning, sequencing, and molecular analysis of the acetoacetate decarboxylase gene region from Clostridium acetobutylicum. PUBMED:2254264 EPMC:2254264
Internal database links
|Similarity to PfamA using HHSearch:||DUF2071|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR010451
Acetoacetate decarboxylase (ADC) is involved in solventogenesis in certain bacteria, which occurs at the end of the exponential growth phase when there is a metabolic switch from classical sugar fermentation with the production of acetate and butyrate to the re-internalisation and oxidation of these acids to acetate and butanol [PUBMED:11824611]. In Clostridium, SpoOA controls the switch from acid to solvent production. A SpoAO-binding motif occurs in the gene encoding ADC [PUBMED:10972834].
This family also contains the fungal decarboxylase DEC1 encoded by the Tox1B locus, which along with the Tox1A gene product is required for the production of the polyketide T-toxin. The pathogenic fungus Cochliobolus heterostrophus (Drechslera maydis) requires the T-toxin for high virulence to maize with T-cytoplasm [PUBMED:12236595].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||carboxy-lyase activity (GO:0016831)|
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.
|Seed source:||Pfam-B_12720 (release 9.0)|
|Number in seed:||72|
|Number in full:||670|
|Average length of the domain:||225.10 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||74.15 %|
|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:||6|
|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 ADC domain has been found. There are 20 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...