Summary: DALR domain
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Aminoacyl tRNA synthetase Edit Wikipedia article
|Anticodon-binding domain of tRNA|
leucyl-tRNA synthetase from Thermus thermophilus complexed with a post-transfer editing substrate analogue
|SCOPe||1ivs / SUPFAM|
|DALR anticodon binding domain 1|
Thermus thermophilus arginyl-trna synthetase
|SCOPe||1bs2 / SUPFAM|
|DALR anticodon binding domain 2|
crystal structure of cysteinyl-tRNA synthetase binary complex with tRNACys
An aminoacyl-tRNA synthetase (aaRS or ARS), also called tRNA-ligase, is an enzyme that attaches the appropriate amino acid onto its tRNA. It does so by catalyzing the esterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA. In humans, the 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases, one for each amino acid of the genetic code.
This is sometimes called "charging" or "loading" the tRNA with the amino acid. Once the tRNA is charged, a ribosome can transfer the amino acid from the tRNA onto a growing peptide, according to the genetic code. Aminoacyl tRNA therefore plays an important role in RNA translation, the expression of genes to create proteins.
As genetic efficiency evolved in higher organisms, 13 new domains with no obvious association with the catalytic activity of aaRSs genes have been added.
The synthetase first binds ATP and the corresponding amino acid (or its precursor) to form an aminoacyl-adenylate, releasing inorganic pyrophosphate (PPi). The adenylate-aaRS complex then binds the appropriate tRNA molecule's D arm, and the amino acid is transferred from the aa-AMP to either the 2'- or the 3'-OH of the last tRNA nucleotide (A76) at the 3'-end.
The mechanism can be summarized in the following reaction series:
- Amino Acid + ATP â†’ Aminoacyl-AMP + PPi
- Aminoacyl-AMP + tRNA â†’ Aminoacyl-tRNA + AMP
Summing the reactions, the highly exergonic overall reaction is as follows:
- Amino Acid + tRNA + ATP â†’ Aminoacyl-tRNA + AMP + PPi
Some synthetases also mediate an editing reaction to ensure high fidelity of tRNA charging. If the incorrect tRNA is added (aka. the tRNA is found to be improperly charged), the aminoacyl-tRNA bond is hydrolyzed. This can happen when two amino acids have different properties even if they have similar shapesâ€”as is the case with Valine and Threonine.
The accuracy of aminoacyl-tRNA synthetase is so high that it is often paired with the word â€œsuperspecificityâ€ when it is compared to other enzymes that are involved in metabolism. Although not all synthetases have a domain with the sole purpose of editing, they make up for it by having specific binding and activation of their affiliated amino acids. Another contribution to the accuracy of these synthetases is the ratio of concentrations of aminoacyl-tRNA synthetase and its cognate tRNA. Since tRNA synthetase improperly acylates the tRNA when the synthetase is overproduced, a limit must exist on the levels of aaRSs and tRNAs in vivo.
- Class I has two highly conserved sequence motifs. It aminoacylates at the 2'-OH of a terminal adenosine nucleotide on tRNA, and it is usually monomeric or dimeric (one or two subunits, respectively).
- Class II has three highly conserved sequence motifs. It aminoacylates at the 3'-OH of a terminal adenosine on tRNA, and is usually dimeric or tetrameric (two or four subunits, respectively). Although phenylalanine-tRNA synthetase is class II, it aminoacylates at the 2'-OH.
Regardless of where the aminoacyl is initially attached to the nucleotide, the 2'-O-aminoacyl-tRNA will ultimately migrate to the 3' position via transesterification.
Both classes of aminoacyl-tRNA synthetases are multidomain proteins. In a typical scenario, an aaRS consists of a catalytic domain (where both the above reactions take place) and an anticodon binding domain (which interacts mostly with the anticodon region of the tRNA). Transfer-RNAs for different amino acids differ not only in their anticodon but also at other points, giving them slightly different overall configurations. The aminoacyl-tRNA synthetases recognize the correct tRNAs primarily through their overall configuration, not just through their anticodon. In addition, some aaRSs have additional RNA binding domains and editing domains that cleave incorrectly paired aminoacyl-tRNA molecules.
The catalytic domains of all the aaRSs of a given class are found to be homologous to one another, whereas class I and class II aaRSs are unrelated to one another. The class I aaRSs have the ubiquitous Rossmann fold and have the parallel beta-strands architecture, whereas the class II aaRSs have a unique fold made up of antiparallel beta-strands.
Aminoacyl-tRNA synthetases have been kinetically studied, showing that Mg2+ ions play an active catalytic role and therefore aaRs have a degree of magnesium dependence. Increasing the Mg2+ concentration leads to an increase in the equilibrium constants for the aminoacyl-tRNA synthetasesâ€™ reactions. Although this trend was seen in both class I and class II synthetases, the magnesium dependence for the two classes are very distinct. Class II synthetases have two or three (more frequently three) Mg2+ ions, while class I only requires one Mg2+ ion.
Beside their lack of overall sequence and structure similarity, class I and class II synthetases feature different ATP recognition mechanisms. While class I binds via interactions mediated by backbone hydrogen bonds, class II uses a pair of arginine residues to establish salt bridges to its ATP ligand. This oppositional implementation is manifested in two structural motifs, the Backbone Brackets and Arginine Tweezers, which are observable in all class I and class II structures, respectively. The high structural conservation of these motifs suggest that they must have been present since ancient times.
Most of the aaRSs of a given specificity are evolutionarily closer to one another than to aaRSs of another specificity. However, AsnRS and GlnRS group within AspRS and GluRS, respectively. Most of the aaRSs of a given specificity also belong to a single class. However, there are two distinct versions of the LysRS - one belonging to the class I family and the other belonging to the class II family.
The molecular phylogenies of aaRSs are often not consistent with accepted organismal phylogenies. That is, they violate the so-called canonical phylogenetic pattern shown by most other enzymes for the three domains of life - Archaea, Bacteria, and Eukarya. Furthermore, the phylogenies inferred for aaRSs of different amino acids often do not agree with one another. In addition, aaRS paralogs within the same species show a high degree of divergence between them. These are clear indications that horizontal transfer has occurred several times during the evolutionary history of aaRSs.
A widespread belief in the evolutionary stability of this superfamily, meaning that every organism has all the aaRSs for their corresponding aminoacids is misconceived. A large-scale genomic analysis on ~2500 prokaryotic genomes showed that many of them miss one or more aaRS genes whereas many genomes have 1 or more paralogs. AlaRS, GlyRS, LeuRS, IleRS and ValRS are the most evolutionarily stable members of the family. GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genomes.
With the exception of AlaRS, it has been discovered that 19 out of the 20 human aaRSs have added at least one new domain or motif. These new domains and motifs vary in function and are observed in various forms of life. A common novel function within human aaRSs is providing additional regulation of biological processes. There exists a theory that the increasing number of aaRSs that add domains is due to the continuous evolution of higher organisms with more complex and efficient building blocks and biological mechanisms. One key piece of evidence to this theory is that after a new domain is added to an aaRS, the domain becomes fully integrated. This new domainâ€™s functionality is conserved from that point on.
Application in biotechnology
In some of the aminoacyl tRNA synthetases, the cavity that holds the amino acid can be mutated and modified to carry unnatural amino acids synthesized in the lab, and to attach them to specific tRNAs. This expands the genetic code, beyond the twenty canonical amino acids found in nature, to include an unnatural amino acid as well. The unnatural amino acid is coded by a nonsense (TAG, TGA, TAA) triplet, a quadruplet codon, or in some cases a redundant rare codon. The organism that expresses the mutant synthetase can then be genetically programmed to incorporate the unnatural amino acid into any desired position in any protein of interest, allowing biochemists or structural biologists to probe or change the protein's function. For instance, one can start with the gene for a protein that binds a certain sequence of DNA, and, by directing an unnatural amino acid with a reactive side-chain into the binding site, create a new protein that cuts the DNA at the target-sequence, rather than binding it.
By mutating aminoacyl tRNA synthetases, chemists have expanded the genetic codes of various organisms to include lab-synthesized amino acids with all kinds of useful properties: photoreactive, metal-chelating, xenon-chelating, crosslinking, spin-resonant, fluorescent, biotinylated, and redox-active amino acids. Another use is introducing amino acids bearing reactive functional groups for chemically modifying the target protein.
Certain diseasesâ€™ causation (such as neuronal pathologies, cancer, disturbed metabolic conditions, and autoimmune disorders) have been correlated to specific mutations of aminoacyl-tRNA synthetases. Charcot-Marie-Tooth (CMT) is the most frequent heritable disorder of the peripheral nervous system (a neuronal disease) and is caused by a heritable mutation in glycol-tRNA and tyrosyl-tRNA. Diabetes, a metabolic disease, induces oxidative stress, which triggers a build up of mitochondrial tRNA mutations. It has also been discovered that tRNA synthetases may be partially involved in the etiology of cancer. A high level of expression or modification of aaRSs has been observed within a range of cancers. A common outcome from mutations of aaRSs is a disturbance of dimer shape/formation which has a direct relationship with its function. These correlations between aaRSs and certain diseases have opened up a new door to synthesizing therapeutics.
The novel domain additions to aaRS genes are accretive and progressive up the Tree of Life. The strong evolutionary pressure for these small non-catalytic protein domains suggested their importance. Findings beginning in 1999 and later revealed a previously unrecognized layer of biology: these proteins control gene expression within the cell of origin, and when released exert homeostatic and developmental control in specific human cell types, tissues and organs during adult or fetal development or both, including pathways associated with angiogenesis, inflammation, the immune response, the mechanistic target of rapamycin (mTOR) signalling, apoptosis, tumorigenesis, and interferon gamma (IFN-Î³) and p53 signalling.
Mutations in the mitochondrial enzyme have been associated with a number of genetic disorders including Leigh syndrome, West syndrome and CAGSSS (cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss and skeletal dysphasia syndrome).
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- Delarue, M (1995). "Aminoacyl-tRNA synthetases". Structural Biology. 5: 48â€“55.
- Appendix A of Vladimir shCherbak and Maxim Makukov (May 2013). "The "Wow! signal" of the terrestrial genetic code" (PDF). Icarus. doi:10.1016/j.icarus.2013.02.017.
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- Wolf YI, Aravind L, Grishin NV, Koonin EV (August 1999). "Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events". Genome Research. 9 (8): 689â€“710. doi:10.1101/gr.9.8.689. PMID 10447505.
- Airas RK (December 2007). "Magnesium dependence of the measured equilibrium constants of aminoacyl-tRNA synthetases". Biophysical Chemistry. 131 (1â€“3): 29â€“35. doi:10.1016/j.bpc.2007.08.006. PMID 17889423.
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- Kaiser F, Bittrich S, Salentin S, Leberecht C, Haupt VJ, Krautwurst S, Schroeder M, Labudde D (April 2018). "Backbone Brackets and Arginine Tweezers delineate Class I and Class II aminoacyl tRNA synthetases". PLoS Computational Biology. 14 (4): e1006101. doi:10.1371/journal.pcbi.1006101. PMC 5919687. PMID 29659563.
- Woese CR, Olsen GJ, Ibba M, SÃ¶ll D (March 2000). "Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process". Microbiology and Molecular Biology Reviews. 64 (1): 202â€“36. doi:10.1128/MMBR.64.1.202-236.2000. PMC 98992. PMID 10704480.
- Chaliotis A, Vlastaridis P, Mossialos D, Ibba M, Becker HD, Stathopoulos C, Amoutzias GD (February 2017). "The complex evolutionary history of aminoacyl-tRNA synthetases". Nucleic Acids Research. 45 (3): 1059â€“1068. doi:10.1093/nar/gkw1182. PMC 5388404. PMID 28180287.
- Guo M, Yang XL, Schimmel P (September 2010). "New functions of aminoacyl-tRNA synthetases beyond translation". Nature Reviews. Molecular Cell Biology. 11 (9): 668â€“74. doi:10.1038/nrm2956. PMC 3042954. PMID 20700144.
- Lee SW, Cho BH, Park SG, Kim S (August 2004). "Aminoacyl-tRNA synthetase complexes: beyond translation". Journal of Cell Science. 117 (Pt 17): 3725â€“34. doi:10.1242/jcs.01342. PMID 15286174.
- Peter G. Schultz, Expanding the genetic code
- Xie W, Schimmel P, Yang XL (December 2006). "Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease". Acta Crystallographica Section F. 62 (Pt 12): 1243â€“6. doi:10.1107/S1744309106046434. PMC 2225372. PMID 17142907.
- Kwon NH, Kang T, Lee JY, Kim HH, Kim HR, Hong J, Oh YS, Han JM, Ku MJ, Lee SY, Kim S (December 2011). "Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3". Proceedings of the National Academy of Sciences of the United States of America. 108 (49): 19635â€“40. doi:10.1073/pnas.1103922108. PMC 3241768. PMID 22106287.
- Park SG, Schimmel P, Kim S (August 2008). "Aminoacyl tRNA synthetases and their connections to disease". Proceedings of the National Academy of Sciences of the United States of America. 105 (32): 11043â€“9. doi:10.1073/pnas.0802862105. PMC 2516211. PMID 18682559.
- Ludmerer SW, Schimmel P (August 1987). "Construction and analysis of deletions in the amino-terminal extension of glutamine tRNA synthetase of Saccharomyces cerevisiae". The Journal of Biological Chemistry. 262 (22): 10807â€“13. PMID 3301842.
- Eriani G, Delarue M, Poch O, Gangloff J, Moras D (September 1990). "Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs". Nature. 347 (6289): 203â€“6. doi:10.1038/347203a0. PMID 2203971.
- Cusack S (December 1997). "Aminoacyl-tRNA synthetases". Current Opinion in Structural Biology. 7 (6): 881â€“9. doi:10.1016/s0959-440x(97)80161-3. PMID 9434910.
- Lo WS, Gardiner E, Xu Z, Lau CF, Wang F, Zhou JJ, Mendlein JD, Nangle LA, Chiang KP, Yang XL, Au KF, Wong WH, Guo M, Zhang M, Schimmel P (July 2014). "Human tRNA synthetase catalytic nulls with diverse functions". Science. 345 (6194): 328â€“32. doi:10.1126/science.1252943. PMC 4188629. PMID 25035493.
- Wakasugi K, Schimmel P (April 1999). "Two distinct cytokines released from a human aminoacyl-tRNA synthetase". Science. 284 (5411): 147â€“51. doi:10.1126/science.284.5411.147. PMID 10102815.
- Lareau LF, Green RE, Bhatnagar RS, Brenner SE (June 2004). "The evolving roles of alternative splicing". Current Opinion in Structural Biology. 14 (3): 273â€“82. doi:10.1016/j.sbi.2004.05.002. PMID 15193306.
- Wakasugi K, Slike BM, Hood J, Otani A, Ewalt KL, Friedlander M, Cheresh DA, Schimmel P (January 2002). "A human aminoacyl-tRNA synthetase as a regulator of angiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 99 (1): 173â€“7. doi:10.1073/pnas.012602099. PMC 117534. PMID 11773626.
- Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P (January 2005). "VE-cadherin links tRNA synthetase cytokine to anti-angiogenic function". The Journal of Biological Chemistry. 280 (4): 2405â€“8. doi:10.1074/jbc.C400431200. PMID 15579907.
- Kawahara A, Stainier DY (August 2009). "Noncanonical activity of seryl-transfer RNA synthetase and vascular development". Trends in Cardiovascular Medicine. 19 (6): 179â€“82. doi:10.1016/j.tcm.2009.11.001. PMC 2846333. PMID 20211432.
- Zhou Q, Kapoor M, Guo M, Belani R, Xu X, Kiosses WB, Hanan M, Park C, Armour E, Do MH, Nangle LA, Schimmel P, Yang XL (January 2010). "Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality". Nature Structural & Molecular Biology. 17 (1): 57â€“61. doi:10.1038/nsmb.1706. PMC 3042952. PMID 20010843.
- Park SG, Kim HJ, Min YH, Choi EC, Shin YK, Park BJ, Lee SW, Kim S (May 2005). "Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response". Proceedings of the National Academy of Sciences of the United States of America. 102 (18): 6356â€“61. doi:10.1073/pnas.0500226102. PMC 1088368. PMID 15851690.
- Arif A, Jia J, Moodt RA, DiCorleto PE, Fox PL (January 2011). "Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control". Proceedings of the National Academy of Sciences of the United States of America. 108 (4): 1415â€“20. doi:10.1073/pnas.1011275108. PMC 3029695. PMID 21220307.
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- Vona B, Maroofian R, Bellacchio E, Najafi M, Thompson K, Alahmad A, He L, Ahangari N, Rad A, Shahrokhzadeh S, Bahena P, Mittag F, Traub F, Movaffagh J, Amiri N, Doosti M, Boostani R, Shirzadeh E, Haaf T, Diodato D, Schmidts M, Taylor RW, Karimiani EG (2018) Expanding the clinical phenotype of IARS2-related mitochondrial disease. BMC Med Genet 19(1):196. doi: 10.1186/s12881-018-0709-3
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.
DALR domain Provide feedback
This DALR domain is found in cysteinyl-tRNA-synthetases .
Wolf YI, Aravind L, Grishin NV, Koonin EV; , Genome Res 1999;9:689-710.: Evolution of aminoacyl-tRNA synthetases--analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events. PUBMED:10447505 EPMC:10447505
This tab holds annotation information from the InterPro database.
InterPro entry IPR015273
The aminoacyl-tRNA synthetase (also known as aminoacyl-tRNA ligase) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction [PUBMED:10704480,PUBMED:12458790]. These proteins differ widely in size and oligomeric state, and have limited sequence homology [PUBMED:2203971]. The 20 aminoacyl-tRNA synthetases are divided into two classes, I and II. Class I aminoacyl-tRNA synthetases contain a characteristic Rossman fold catalytic domain and are mostly monomeric [PUBMED:10673435]. Class II aminoacyl-tRNA synthetases share an anti-parallel beta-sheet fold flanked by alpha-helices [PUBMED:8364025], and are mostly dimeric or multimeric, containing at least three conserved regions [PUBMED:8274143, PUBMED:2053131, PUBMED:1852601]. However, tRNA binding involves an alpha-helical structure that is conserved between class I and class II synthetases. In reactions catalysed by the class I aminoacyl-tRNA synthetases, the aminoacyl group is coupled to the 2'-hydroxyl of the tRNA, while, in class II reactions, the 3'-hydroxyl site is preferred. The synthetases specific for arginine, cysteine, glutamic acid, glutamine, isoleucine, leucine, methionine, tyrosine, tryptophan, valine, and some lysine synthetases (non-eukaryotic group) belong to class I synthetases. The synthetases specific for alanine, asparagine, aspartic acid, glycine, histidine, phenylalanine, proline, serine, threonine,and some lysine synthetases (non-archaeal group), belong to class-II synthetases. Based on their mode of binding to the tRNA acceptor stem, both classes of tRNA synthetases have been subdivided into three subclasses, designated 1a, 1b, 1c and 2a, 2b, 2c [PUBMED:10447505].
This DALR domain is found in cysteinyl-tRNA-synthetases [PUBMED:10447505].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||cytoplasm (GO:0005737)|
|Molecular function||cysteine-tRNA ligase activity (GO:0004817)|
|ATP binding (GO:0005524)|
|nucleotide binding (GO:0000166)|
|Biological process||cysteinyl-tRNA aminoacylation (GO:0006423)|
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:
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This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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We make a range of alignments for each Pfam-A family:
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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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.
|Author:||Sammut SJ , Bateman A|
|Number in seed:||80|
|Number in full:||7096|
|Average length of the domain:||63.20 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||13.27 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||11|
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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 DALR_2 domain has been found. There are 6 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 sequence.
Loading structure mapping...