Summary: Adenylate kinase, active site lid
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 "Adenylate kinase". 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 firstname.lastname@example.org 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.
Adenylate kinase Edit Wikipedia article
3D ribbon/surface model of adenylate kinase in complex with bis(adenosine)tetraphosphate (ADP-ADP)
Bacillus stearothermophilus adenylate kinase
Adenylate kinase (EC 22.214.171.124) (also known as ADK or myokinase) is a phosphotransferase enzyme that catalyzes the interconversion of adenine nucleotides, and plays an important role in cellular energy homeostasis.
- 1 Substrate and products
- 2 ADK isozymes
- 3 Subfamilies
- 4 Isozymes
- 5 Mechanism
- 6 Structure
- 7 Function
- 8 Disease relevance
- 9 Plastidial ADK deficiency in Arabidopsis thaliana
- 10 References
- 11 External links
Substrate and products
The reaction catalyzed is:
The equilibrium constant varies with condition, but is close to 1. Thus, the ΔGo for this reaction is close to zero. In muscle of a variety of species of vertebrates and invertebrates, the concentration of ATP is typically 7-10 times that of ADP, and usually greater than 100 times that of AMP. The rate of oxidative phosphorylation is controlled by the availability of ADP. Thus, the mitochondrion attempts to keep ATP levels high due to the combined action of adenylate kinase and the controls on oxidative phosphorylation.
This is an essential reaction for many processes in living cells. Two ADK isozymes have been identified in mammalian cells. These specifically bind AMP and favor binding to ATP over other nucleotide triphosphates (AK1 is cytosolic and AK2 is located in the mitochondria). A third ADK has been identified in bovine heart and human cells, this is a mitochondrial GTP:AMP phosphotransferase, also specific for the phosphorylation of AMP, but can only use GTP or ITP as a substrate. ADK has also been identified in different bacterial species and in yeast. Two further enzymes are known to be related to the ADK family, i.e. yeast uridine monophosphokinase and slime mold UMP-CMP kinase. Within the ADK family there are several conserved regions, including the ATP-binding domains. One of the most conserved areas includes an Arg residue, whose modification inactivates the enzyme, together with an Asp that resides in the catalytic cleft of the enzyme and participates in a salt bridge.
- Adenylate kinase, subfamily IPR006259
- UMP-CMP kinase IPR006266
- Adenylate kinase, isozyme 1 IPR006267
Human genes encoding proteins with adenylate kinase include:
In Escherichia coli, the crystal structure of ADK was analyzed in a 2005 study. The crystal structure revealed that ADK was complexed with diadenosine pentaphosphate (AP5A), Mg2+, and 4 coordinated water molecules. ATP adenine and ribose moieties are loosely bound to ADK. The phosphates in ATP are strongly bound to surrounding residues. Mg2+, coordination waters, and surrounding charged residues maintain the geometry and distances of the AMP α-phosphate and ATP β- and γ-phosphates. And, this is sufficient to support an associative reaction mechanism for phosphoryl transfer. ADK catalyzes the transfer of a phosphoryl group from ATP to AMP by nucleophilic attack on the γ-phosphate of ATP.
Flexibility and plasticity allow proteins to bind to ligands, form oligomers, aggregate, and perform mechanical work. Large conformational changes in proteins play an important role in cellular signaling. Adenylate Kinase is a signal transducing protein; thus, the balance between conformations regulates protein activity. ADK has a locally unfolded state that becomes depopulated upon binding.
A 2007 study by Whitford et al. shows the conformations of ADK when binding with ATP or AMP. The study shows that there are three relevant conformations or structures of ADK—CORE, Open, and Closed. In ADK, there are two small domains called the LID and NMP. ATP binds in the pocket formed by the LID and CORE domains. AMP binds in the pocket formed by the NMP and CORE domains.
The study also reported findings that show that localized regions of a protein unfold during conformational transitions. This mechanism reduces the strain and enhances catalytic efficiency. Local unfolding is the result of competing strain energies in the protein. The interconversion between inactive (open) and active (closed) conformations is rate limiting for catalysis.
ADK uses AMP metabolic signals produced or downregulated during exercise, stress response, food consumption, hormone changes. ADK relays deliver AMP signals to metabolic sensors. It facilitates decoding of cellular information by catalyzing nucleotide exchange in the intimate “sensing zone” of metabolic sensors.
Through a chain of sequential reactions, ADK facilitates transfer and utilization of γ- and β-phosphoryls in the ATP molecule.
The energy of two high-energy phosphoryls, γ- and β-phosphoryls in the ATP molecule, is made available by the ADK present in mitochondrial and myofibrillar compartments. ATP and AMP are transferred between ATP-production and ATP-consumption sites that involve multiple, sequential phosphotransfer relays. This results in a flux wave propagation along groups of ADK molecules. This ligand conduction mechanism facilitates metabolic flux without apparent changes in metabolite concentrations.
ADK reads the cellular energy state, generates, tunes, and communicates AMP signals to metabolic sensors. In this way, ADK is able to convey information about the overall energy balance. AMP-sensors inhibit ATP consumption and promote ATP production.
Nucleoside diphosphate kinase deficiency
Nucleoside diphosphate (NDP) kinase catalyzes in vivo ATP-dependent synthesis of riobo- and deoxyribonucleoside triphosphates. In mutated Escherichia coli that had a disrupted nucleoside diphosphate kinase, adenylate kinase performed dual enzymatic functions. ADK complements nucleoside diphosphate kinase deficiency.
Adenylate kinase deficiency in the erythrocyte is associated with hemolytic anemia. This is a rare hereditary erythroenzymopathy that, in some cases, is associated with mental retardation and psychomotor impairment. At least two patients have exhibited neonatal icterus and splenomegaly and required blood transfusions due to this deficiency. In another patient, an abnormal fragment with homozygous and heterozygous A-->G substitutions at codon 164 caused severe erythrocyte ADK deficiency. Two siblings had erythrocyte ADK deficiency, but one did not have evidence of hemolysis.
AK1 and post-ischemic coronary reflow
Knock out of AK1 disrupts the synchrony between inorganic phosphate and turnover at ATP-consuming sites and ATP synthesis sites. This reduces the energetic signal communication in the post-ischemic heart and precipitates inadequate coronary reflow flowing ischemia-reperfusion.
Adenylate Kinase 2 (AK2) deficiency in humans causes hematopoietic defects associated with sensorineural deafness. Recticular dysgenesis is an autosomal recessive form of human combined immunodeficiency. It is also characterized by an impaired lymphoid maturation and early differentiation arrest in the myeloid lineage. AK2 deficiency results in absent or a large decrease in the expression of proteins. AK2 is specifically expressed in the stria vascularis of the inner ear which indicates why individuals with an AK2 deficiency will have sensorineural deafness.
AK1 genetic ablation decreases tolerance to metabolic stress. AK1 deficiency induces fiber-type specific variation in groups of transcripts in glycolysis and mitochondrial metabolism. This supports muscle energy metabolism.
Plastidial ADK deficiency in Arabidopsis thaliana
- The NIST Thermodynamics of Enzyme-Catalyzed Reactions database, http://xpdb.nist.gov/enzyme_thermodynamics/enzyme1.pl, Goldberg RN, Tewari YB, Bhat TN, "Thermodynamics of Enzyme-Catalyzed Reactions -a Database for Quantitative Biochemistry", Bioinformatics 2004;20(16):2874-2877, http://www.ncbi.nlm.nih.gov/pubmed/15145806, gives equilibrium constants, search for adenylate kinase under enzymes
- Beis I, Newsholme EA (October 1975). "The contents of adenine nucleotides, phosphagens and some glycolytic intermediates in resting muscles from vertebrates and invertebrates". Biochem. J. 152 (1): 23–32. PMC 1172435. PMID 1212224.
- Schulz GE, Frank R, Tomasselli AG, Noda LH, Wieland B (1984). "The amino acid sequence of GTP:AMP phosphotransferase from beef-heart mitochondria. Extensive homology with cytosolic adenylate kinase". Eur. J. Biochem. 143 (2): 331–339. doi:10.1111/j.1432-1033.1984.tb08376.x. PMID 6088234.
- Tomasselli AG, Noda LH (1979). "Mitochondrial GTP-AMP phosphotransferase. 2. Kinetic and equilibrium dialysis studies". Eur. J. Biochem. 93 (2): 263–270. doi:10.1111/j.1432-1033.1979.tb12819.x. PMID 218813.
- Cooper AJ, Friedberg EC (1992). "A putative second adenylate kinase-encoding gene from the yeast Saccharomyces cerevisiae". Gene 114 (1): 145–148. doi:10.1016/0378-1119(92)90721-Z. PMID 1587477.
- Krishnamurthy, H.; Lou, H.; Kimple, A.; Vieille, C.; Cukier, RI. (Jan 2005). "Associative mechanism for phosphoryl transfer: a molecular dynamics simulation of Escherichia coli adenylate kinase complexed with its substrates.". Proteins 58 (1): 88–100. doi:10.1002/prot.20301. PMID 15521058.
- Whitford PC, Miyashita O, Levy Y, Onuchic JN (March 2007). "Conformational transitions of adenylate kinase: switching by cracking". J. Mol. Biol. 366 (5): 1661–71. doi:10.1016/j.jmb.2006.11.085. PMC 2561047. PMID 17217965.
- Schrank, TP.; Bolen, DW.; Hilser, VJ. (Oct 2009). "Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins.". Proc Natl Acad Sci U S A 106 (40): 16984–9. doi:10.1073/pnas.0906510106. PMID 19805185.
- Daily, MD.; Phillips, GN.; Cui, Q. (Jul 2010). "Many local motions cooperate to produce the adenylate kinase conformational transition.". J Mol Biol 400 (3): 618–31. doi:10.1016/j.jmb.2010.05.015. PMID 20471396.
- Olsson, U.; Wolf-Watz, M. (2010). "Overlap between folding and functional energy landscapes for adenylate kinase conformational change.". Nat Commun 1 (8): 111. doi:10.1038/ncomms1106. PMID 21081909.
- Dzeja P, Terzic A (April 2009). "Adenylate kinase and AMP signaling networks: Metabolic monitoring, signal communication and body energy sensing". Int J Mol Sci 10 (4): 1729–72. doi:10.3390/ijms10041729. PMC 2680645. PMID 19468337.
- Lu, Q.; Inouye, M. (Jun 1996). "Adenylate kinase complements nucleoside diphosphate kinase deficiency in nucleotide metabolism.". Proc Natl Acad Sci U S A 93 (12): 5720–5. doi:10.1073/pnas.93.12.5720. PMID 8650159.
- Matsuura, S.; Igarashi, M.; Tanizawa, Y.; Yamada, M.; Kishi, F.; Kajii, T.; Fujii, H.; Miwa, S.; Sakurai, M.; Nakazawa, A. (Jun 1989). "Human adenylate kinase deficiency associated with hemolytic anemia. A single base substitution affecting solubility and catalytic activity of the cytosolic adenylate kinase.". J Biol Chem 264 (17): 10148–55. PMID 2542324.
- Abrusci, P.; Chiarelli, LR.; Galizzi, A.; Fermo, E.; Bianchi, P.; Zanella, A.; Valentini, G. (Aug 2007). "Erythrocyte adenylate kinase deficiency: characterization of recombinant mutant forms and relationship with nonspherocytic hemolytic anemia.". Exp Hematol 35 (8): 1182–9. doi:10.1016/j.exphem.2007.05.004. PMID 17662886.
- Corrons, JL.; Garcia, E.; Tusell, JJ.; Varughese, KI.; West, C.; Beutler, E. (Jul 2003). "Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118GA, 190GA, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia.". Blood 102 (1): 353–6. doi:10.1182/blood-2002-07-2288. PMID 12649162.
- Qualtieri, A.; Pedace, V.; Bisconte, MG.; Bria, M.; Gulino, B.; Andreoli, V.; Brancati, C. (Dec 1997). "Severe erythrocyte adenylate kinase deficiency due to homozygous A-->G substitution at codon 164 of human AK1 gene associated with chronic haemolytic anaemia.". Br J Haematol 99 (4): 770–6. PMID 9432020.
- Beutler, E.; Carson, D.; Dannawi, H.; Forman, L.; Kuhl, W.; West, C.; Westwood, B. (Aug 1983). "Metabolic compensation for profound erythrocyte adenylate kinase deficiency. A hereditary enzyme defect without hemolytic anemia.". J Clin Invest 72 (2): 648–55. doi:10.1172/JCI111014. PMID 6308059.
- Dzeja, PP.; Bast, P.; Pucar, D.; Wieringa, B.; Terzic, A. (Oct 2007). "Defective metabolic signaling in adenylate kinase AK1 gene knock-out hearts compromises post-ischemic coronary reflow.". J Biol Chem 282 (43): 31366–72. doi:10.1074/jbc.M705268200. PMID 17704060.
- Lagresle-Peyrou C, Six EM, Picard C, et al. (January 2009). "Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness". Nat. Genet. 41 (1): 106–11. doi:10.1038/ng.278. PMC 2612090. PMID 19043416.
- Janssen, E.; de Groof, A.; Wijers, M.; Fransen, J.; Dzeja, PP.; Terzic, A.; Wieringa, B. (Apr 2003). "Adenylate kinase 1 deficiency induces molecular and structural adaptations to support muscle energy metabolism.". J Biol Chem 278 (15): 12937–45. doi:10.1074/jbc.M211465200. PMID 12562761.
- Carrari, F.; Coll-Garcia, D.; Schauer, N.; Lytovchenko, A.; Palacios-Rojas, N.; Balbo, I.; Rosso, M.; Fernie, AR. (Jan 2005). "Deficiency of a plastidial adenylate kinase in Arabidopsis results in elevated photosynthetic amino acid biosynthesis and enhanced growth.". Plant Physiol 137 (1): 70–82. doi:10.1104/pp.104.056143. PMID 15618410.
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.
Adenylate kinase, active site lid Provide feedback
Comparisons of adenylate kinases have revealed a particular divergence in the active site lid. In some organisms, particularly the Gram-positive bacteria, residues in the lid domain have been mutated to cysteines and these cysteine residues are responsible for the binding of a zinc ion. The bound zinc ion in the lid domain, is clearly structurally homologous to Zinc-finger domains. However, it is unclear whether the adenylate kinase lid is a novel zinc-finger DNA/RNA binding domain, or that the lid bound zinc serves a purely structural function .
Berry MB, Phillips GN Jr; , Proteins 1998;32:276-288.: Crystal structures of Bacillus stearothermophilus adenylate kinase with bound Ap5A, Mg2+ Ap5A, and Mn2+ Ap5A reveal an intermediate lid position and six coordinate octahedral geometry for bound Mg2+ and Mn2+. PUBMED:9715904 EPMC:9715904
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR007862
Adenylate kinases (ADK; EC) are phosphotransferases that catalyse the Mg-dependent reversible conversion of ATP and AMP to two molecules of ADP, an essential reaction for many processes in living cells. In large variants of adenylate kinase, the AMP and ATP substrates are buried in a domain that undergoes conformational changes from an open to a closed state when bound to substrate; the ligand is then contained within a highly specific environment required for catalysis. Adenylate kinase is a 3-domain protein consisting of a large central CORE domain flanked by a LID domain on one side and the AMP-binding NMPbind domain on the other [PUBMED:17299745]. The LID domain binds ATP and covers the phosphates at the active site. The substrates first bind the CORE domain, followed by closure of the active site by the LID and NMPbind domains.
Comparisons of adenylate kinases have revealed a particular divergence in the active site lid. In some organisms, particularly the Gram-positive bacteria, residues in the lid domain have been mutated to cysteines and these cysteine residues (two CX(n)C motifs) are responsible for the binding of a zinc ion. The bound zinc ion in the lid domain is clearly structurally homologous to Zinc-finger domains. However, it is unclear whether the adenylate kinase lid is a novel zinc-finger DNA/RNA binding domain, or that the lid bound zinc serves a purely structural function [PUBMED:9715904].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||adenylate kinase activity (GO:0004017)|
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:||141|
|Number in full:||6209|
|Average length of the domain:||36.00 aa|
|Average identity of full alignment:||57 %|
|Average coverage of the sequence by the domain:||18.92 %|
|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:||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.
There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
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 ADK_lid domain has been found. There are 61 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...