Summary: DALR domain
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 "Aminoacyl tRNA synthetase". 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.
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
|DALR anticodon binding domain 1|
Thermus thermophilus arginyl-trna synthetase
|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 → Aminoacyl-AMP + PPi
- Aminoacyl-AMP + tRNA → Aminoacyl-tRNA + AMP
Summing the reactions, the highly exergonic overall reaction is as follows:
- Amino Acid + tRNA + ATP → 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 shapes—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 “superspecificity” 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 and ensures binding of the correct tRNA to the amino acid). 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 synthetases’ 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 domain’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 diseases’ 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-γ) and p53 signalling.
- ICAARS: B. Pawar, and GPS Raghava (2010) Prediction and classification of aminoacyl tRNA synthetases using PROSITE domains. BMC Genomics 2010, 11:507
- MARSpred: Panwar B, Raghava GP (May 2012). "Predicting sub-cellular localization of tRNA synthetases from their primary structures". Amino Acids. 42 (5): 1703–13. doi:10.1007/s00726-011-0872-8. PMID 21400228.
- Prokaryotic AARS database: Chaliotis et al., (2017). The complex evolutionary history of aminoacyl-tRNA synthetases. Nucleic Acids Res. 2017 Feb 17;45(3):1059-1068. doi:10.1093/nar/gkw1182.
- McClain WH (November 1993). "Rules that govern tRNA identity in protein synthesis". Journal of Molecular Biology. 234 (2): 257–80. doi:10.1006/jmbi.1993.1582. PMID 8230212.
- Swanson R, Hoben P, Sumner-Smith M, Uemura H, Watson L, Söll D (December 1988). "Accuracy of in vivo aminoacylation requires proper balance of tRNA and aminoacyl-tRNA synthetase". Science. 242 (4885): 1548–51. PMID 3144042.
- "tRNA Synthetases". Retrieved 2007-08-18.
- Delarue, M (1995). "Aminoacyl-tRNA synthetases". Structural Biology. 5: 48–55.
- "Molecule of the Month: Aminoacyl-tRNA Synthetases High Fidelity". Retrieved 2013-08-04.
- 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): 689–710. 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 (1–3): 29–35. doi:10.1016/j.bpc.2007.08.006. PMID 17889423.
- Francklyn C, Musier-Forsyth K, Martinis SA (September 1997). "Aminoacyl-tRNA synthetases in biology and disease: new evidence for structural and functional diversity in an ancient family of enzymes". Rna. 3 (9): 954–60. PMID 9292495.
- 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. PMID 29659563.
- Woese CR, Olsen GJ, Ibba M, Söll D (March 2000). "Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process". Microbiology and Molecular Biology Reviews. 64 (1): 202–36. doi:10.1128/MMBR.64.1.202-236.2000. PMC . 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): 1059–1068. doi:10.1093/nar/gkw1182. PMC . 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): 668–74. doi:10.1038/nrm2956. PMC . 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): 3725–34. 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, Structural Biology and Crystallization Communications. 62 (Pt 12): 1243–6. doi:10.1107/S1744309106046434. PMC . 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): 19635–40. doi:10.1073/pnas.1103922108. PMC . 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): 11043–9. doi:10.1073/pnas.0802862105. PMC . 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): 10807–13. 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): 203–6. doi:10.1038/347203a0. PMID 2203971.
- Cusack S (December 1997). "Aminoacyl-tRNA synthetases". Current Opinion in Structural Biology. 7 (6): 881–9. 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): 328–32. doi:10.1126/science.1252943. PMID 25035493.
- Wakasugi K, Schimmel P (April 1999). "Two distinct cytokines released from a human aminoacyl-tRNA synthetase". Science. 284 (5411): 147–51. 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): 273–82. 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): 173–7. doi:10.1073/pnas.012602099. 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): 2405–8. 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): 179–82. doi:10.1016/j.tcm.2009.11.001. 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): 57–61. doi:10.1038/nsmb.1706. 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): 6356–61. doi:10.1073/pnas.0500226102. 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): 1415–20. doi:10.1073/pnas.1011275108. PMID 21220307.
- Guo M, Schimmel P (March 2013). "Essential nontranslational functions of tRNA synthetases". Nature Chemical Biology. 9 (3): 145–53. doi:10.1038/nchembio.1158. PMID 23416400.
- Amino Acyl-tRNA Synthetases at the US National Library of Medicine Medical Subject Headings (MeSH)
- AARS human gene location in the UCSC Genome Browser.
- AARS human gene details in the UCSC Genome Browser.
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:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|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|
|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 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...