Summary: Adenosine-deaminase (editase) 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 "Adenosine deaminase". 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.
Adenosine deaminase Edit Wikipedia article
Ribbon diagram of bovine adenosine deaminase. Zinc ion visible at center. From PDB 1VFL
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
crystal structure of plasmodium yoelii adenosine deaminase (py02076)
|Adenosine deaminase (editase) domain|
|Adenosine/AMP deaminase N-terminal|
Adenosine deaminase (also known as adenosine aminhydrolase, or ADA) is an enzyme (EC 188.8.131.52) involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.
Present in virtually all mammalian cells, its primary function in humans is the development and maintenance of the immune system. However, the full physiological role of ADA is not yet completely understood.
ADA exists in both small form (as a monomer) and large form (as a dimer-complex). In the monomer form, the enzyme is a polypeptide chain, folded into eight strands of parallel α/β barrels, which surround a central deep pocket that is the active site. In addition to the eight central β-barrels and eight peripheral α-helices, ADA also contains five additional helices: residues 19-76 fold into three helices, located between β1 and α1 folds; and two antiparallel carboxy-terminal helices are located across the amino-terminal of the β-barrel.
The ADA active site contains a zinc ion, which is located in the deepest recess of the active site and coordinated by five atoms from His15, His17, His214, Asp295, and the substrate. Zinc is the only cofactor necessary for activity.
The substrate, adenosine, is stabilized and bound to the active site by nine hydrogen bonds. The carboxyl group of Glu217, roughly coplanar with the substrate purine ring, is in position to form a hydrogen bond with N1 of the substrate. The carboxyl group of Asp296, also coplanar with the substrate purine ring, forms hydrogen bond with N7 of the substrate. The NH group of Gly184 is in position to form a hydrogen bond with N3 of the substrate. Asp296 forms bonds both with the Zn2+ ion as well as with 6-OH of the substrate. His238 also hydrogen bonds to substrate 6-OH. The 3'-OH of the substrate ribose forms a hydrogen bond with Asp19, while the 5'-OH forms a hydrogen bond with His17. Two further hydrogen bonds are formed to water molecules, at the opening of the active site, by the 2'-OH and 3'-OH of the substrate.
Due to the recessing of the active inside the enzyme, the substrate once bound is almost completely sequestered from solvent. The surface exposure of the substrate to solvent when bound is 0.5% the surface exposure of the substrate in the free state.
Two proposed mechanism exist for ADA-catalyzed deamination: 1) stereospecific addition-elimination via tetrahedral intermediate or 2) an SN2 reaction. By either mechanism, Zn2+ as a strong electrophile activates a water molecule, which is deprotonated by the basic Asp295 to form the attacking hydroxide. His238 orients the water molecule and stabilizes the charge of the attacking hydroxide. Glu217 is protonated to donate a proton to N1 of the substrate.
Competitive inhibition has been observed for ADA, where the product inosine acts at the competitive inhibitor to enzymatic activity.
ADA is considered one of the key enzymes of purine metabolism. The enzyme has been found in bacteria, plants, invertebrates, vertebrates, and mammals, with high conservation of amino acid sequence. The high degree of amino acid sequence conservation suggests the crucial nature of ADA in the purine salvage pathway.
Primarily, ADA in humans is involved in the development and maintenance of the immune system. However, ADA association has also been observed with epithelial cell differentiation, neurotransmission, and gestation maintenance. It has also been proposed that ADA, in addition to adenosine breakdown, stimulates release of excitatory amino acids and is necessary to the coupling of A1 adenosine receptors and heterotrimeric G proteins.
Some mutations in the gene for adenosine deaminase cause it not to be expressed. The resulting deficiency is one cause of (SCID). Deficient levels of ADA have also been associated with pulmonary inflammation, thymic cell death, and defective T-cell receptor signaling.
Conversely, mutations causing this enzyme to be overexpressed are one cause of .
There are 2 isoforms of ADA: ADA1 and ADA2.
- ADA1 is found in most body cells, particularly lymphocytes and macrophages, where it is present not only in the cytosol and nucleus but also as the ecto- form on the cell membrane attached to dipeptidyl peptidase-4 (aka, CD26). ADA1 is involved mostly in intracellular activity, and exists both in small form (monomer) and large form (dimer). The interconversion of small to large forms is regulated by a 'conversion factor' in the lung.
- ADA2 was first identified in human spleen. It was subsequently found in other tissues including the macrophage where it co-exists with ADA1. The two isoforms regulate the ratio of adenosine to deoxyadenosine potentiating the killing of parasites. ADA2 is found predominantly in the human plasma and serum, and exists solely as a homodimer.
- ADAT (ADAT1, ADAT2, ADAT3) is a tRNA-specific ADA, changing the tRNA to allow for a wobble base pairing.
ADA2 is the predominant form present in human blood plasma and is increased in many diseases, particularly those associated with the immune system: for example rheumatoid arthritis, psoriasis, and sarcoidosis. The plasma ADA2 isoform is also increased in most cancers. ADA2 is not ubiquitous but co-exists with ADA1 only in monocytes-macrophages.
Total plasma ADA can be measured using high performance liquid chromatography or enzymatic or colorimetric techniques. Perhaps the simplest system is the measurement of the ammonia released from adenosine when broken down to inosine. After incubation of plasma with a buffered solution of adenosine the ammonia is reacted with a Berthelot reagent to form a blue colour which is proportionate to the amount of enzyme activity. To measure ADA2, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) is added prior to incubation so as to inhibit the enzymatic activity of ADA1. It is the absence of ADA1 that causes SCID.
- Wilson, D. K.; Rudolph, F. B.; Quiocho, F. A. (1991). "Atomic structure of adenosine deaminase complexed with a transition-state analog: Understanding catalysis and immunodeficiency mutations". Science 252 (5010): 1278–1284. doi:10.1126/science.1925539. PMID 1925539.
- Cristalli, G.; Costanzi, S.; Lambertucci, C.; Lupidi, G.; Vittori, S.; Volpini, R.; Camaioni, E. (2001). "Adenosine deaminase: Functional implications and different classes of inhibitors". Medicinal Research Reviews 21 (2): 105–128. doi:10.1002/1098-1128(200103)21:2<105::AID-MED1002>3.0.CO;2-U. PMID 11223861.
- Daddona, P. E.; Kelley, W. N. (1977). "Human adenosine deaminase. Purification and subunit structure". The Journal of Biological Chemistry 252 (1): 110–115. PMID 13062.
- Glader, B. E.; Backer, K.; Diamond, L. K. (1983). "Elevated Erythrocyte Adenosine Deaminase Activity in Congenital Hypoplastic Anemia". New England Journal of Medicine 309 (24): 1486–1490. doi:10.1056/NEJM198312153092404. PMID 6646173.
- Saboury, A. A.; Divsalar, A.; Jafari, G. A.; Moosavi-Movahedi, A. A.; Housaindokht, M. R.; Hakimelahi, G. H. (2002). "A product inhibition study on adenosine deaminase by spectroscopy and calorimetry". Journal of biochemistry and molecular biology 35 (3): 302–305. doi:10.5483/BMBRep.2002.35.3.302. PMID 12297022.
- Moriwaki, Y.; Yamamoto, T.; Higashino, K. (1999). "Enzymes involved in purine metabolism--a review of histochemical localization and functional implications". Histology and histopathology 14 (4): 1321–1340. PMID 10506947.
- Sanchez JJ, Monaghan G, Børsting C, Norbury G, Morling N, Gaspar HB (2007). "Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry". Ann. Hum. Genet. 71 (Pt 3): 336–47. doi:10.1111/j.1469-1809.2006.00338.x. PMID 17181544.
- Blackburn, M. R.; Kellems, R. E. (2005). Adenosine Deaminase Deficiency: Metabolic Basis of Immune Deficiency and Pulmonary Inflammation. "Advances in Immunology Volume 86". Advances in immunology. Advances in Immunology 86: 1–41. doi:10.1016/S0065-2776(04)86001-2. ISBN 9780120044863. PMID 15705418.
- Apasov, S. G.; Blackburn, M. R.; Kellems, R. E.; Smith, P. T.; Sitkovsky, M. V. (2001). "Adenosine deaminase deficiency increases thymic apoptosis and causes defective T cell receptor signaling". Journal of Clinical Investigation 108 (1): 131–141. doi:10.1172/JCI10360. PMC 209335. PMID 11435465.
- Chottiner EG, Cloft HJ, Tartaglia AP, Mitchell BS (1987). "Elevated adenosine deaminase activity and hereditary hemolytic anemia. Evidence for abnormal translational control of protein synthesis". J. Clin. Invest. 79 (3): 1001–5. doi:10.1172/JCI112866. PMC 424261. PMID 3029177.
- Persico AM, Militerni R, Bravaccio C, et al. (2000). "Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies". Am. J. Med. Genet. 96 (6): 784–90. doi:10.1002/1096-8628(20001204)96:6<784::AID-AJMG18>3.0.CO;2-7. PMID 11121182.
- Cowan, M. J.; Brady, R. O.; Widder, K. J. (1986). "Elevated erythrocyte adenosine deaminase activity in patients with acquired immunodeficiency syndrome". Proceedings of the National Academy of Sciences of the United States of America 83 (4): 1089–1091. doi:10.1073/pnas.83.4.1089. PMC 323016. PMID 3006027.
- Schrader, W. P.; Stacy, A. R. (1977). "Purification and subunit structure of adenosine deaminase from human kidney". The Journal of Biological Chemistry 252 (18): 6409–6415. PMID 893413.
- Schrader WP, Pollara B, Meuwissen HJ (January 1978). "Characterization of the residual adenosine deaminating activity in the spleen of a patient with combined immunodeficiency disease and adenosine deaminase deficiency". Proc. Natl. Acad. Sci. U.S.A. 75 (1): 446–50. doi:10.1073/pnas.75.1.446. PMC 411266. PMID 24216.
- Zavialov AV, Engstrom A (Oct 2005). "Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity". Biochem. J. 391 (1): 51–57. doi:10.1042/BJ20050683. PMC 1237138. PMID 15926889.
- Keegan LP, Leroy A, Sproul D, O'Connell MA (2004). "Adenosine deaminases acting on RNA (ADARs): RNA-editing enzymes". Genome Biol. 5 (2): 209. doi:10.1186/gb-2004-5-2-209. PMC 395743. PMID 14759252.
- Schwartz's principles of surgery, 8th edition, self assessment and board review, chapter 18 question 16
- da Cunha JG (1992). "[Adenosine deaminase. A pluridisciplinary enzyme]". Acta Médica Portuguesa 4 (6): 315–23. PMID 1807098.
- Franco R, Casadó V, Ciruela F, et al. (1997). "Cell surface adenosine deaminase: much more than an ectoenzyme". Prog. Neurobiol. 52 (4): 283–94. doi:10.1016/S0301-0082(97)00013-0. PMID 9247966.
- Valenzuela A, Blanco J, Callebaut C, et al. (1997). "HIV-1 envelope gp120 and viral particles block adenosine deaminase binding to human CD26". Adv. Exp. Med. Biol. 421: 185–92. doi:10.1007/978-1-4757-9613-1_24. PMID 9330696.
- Moriwaki Y, Yamamoto T, Higashino K (1999). "Enzymes involved in purine metabolism--a review of histochemical localization and functional implications". Histol. Histopathol. 14 (4): 1321–40. PMID 10506947.
- Hirschhorn R (1993). "Identification of two new missense mutations (R156C and S291L) in two ADA- SCID patients unusual for response to therapy with partial exchange transfusions". Hum. Mutat. 1 (2): 166–8. doi:10.1002/humu.1380010214. PMID 1284479.
- Berkvens TM, van Ormondt H, Gerritsen EJ, et al. (1990). "Identical 3250-bp deletion between two AluI repeats in the ADA genes of unrelated ADA-SCID patients". Genomics 7 (4): 486–90. doi:10.1016/0888-7543(90)90190-6. PMID 1696926.
- Aran JM, Colomer D, Matutes E, et al. (1991). "Presence of adenosine deaminase on the surface of mononuclear blood cells: immunochemical localization using light and electron microscopy". J. Histochem. Cytochem. 39 (8): 1001–8. doi:10.1177/39.8.1856451. PMID 1856451.
- Bielat K, Tritsch GL (1989). "Ecto-enzyme activity of human erythrocyte adenosine deaminase". Mol. Cell. Biochem. 86 (2): 135–42. doi:10.1007/BF00222613. PMID 2770711.
- Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH (1989). "Identification of a point mutation resulting in a heat-labile adenosine deaminase (ADA) in two unrelated children with partial ADA deficiency". J. Clin. Invest. 83 (2): 497–501. doi:10.1172/JCI113909. PMC 303706. PMID 2783588.
- Murray JL, Perez-Soler R, Bywaters D, Hersh EM (1986). "Decreased adenosine deaminase (ADA) and 5'nucleotidase (5NT) activity in peripheral blood T cells in Hodgkin disease". Am. J. Hematol. 21 (1): 57–66. doi:10.1002/ajh.2830210108. PMID 3010705.
- Wiginton DA, Kaplan DJ, States JC, et al. (1987). "Complete sequence and structure of the gene for human adenosine deaminase". Biochemistry 25 (25): 8234–44. doi:10.1021/bi00373a017. PMID 3028473.
- Akeson AL, Wiginton DA, Dusing MR, et al. (1988). "Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts". J. Biol. Chem. 263 (31): 16291–6. PMID 3182793.
- Glader BE, Backer K (1988). "Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond-Blackfan anaemia and other haematologic diseases". Br. J. Haematol. 68 (2): 165–8. doi:10.1111/j.1365-2141.1988.tb06184.x. PMID 3348976.
- Petersen MB, Tranebjaerg L, Tommerup N, et al. (1987). "New assignment of the adenosine deaminase gene locus to chromosome 20q13 X 11 by study of a patient with interstitial deletion 20q". J. Med. Genet. 24 (2): 93–6. doi:10.1136/jmg.24.2.93. PMC 1049896. PMID 3560174.
- Orkin SH, Goff SC, Kelley WN, Daddona PE (1985). "Transient expression of human adenosine deaminase cDNAs: identification of a nonfunctional clone resulting from a single amino acid substitution". Mol. Cell. Biol. 5 (4): 762–7. PMC 366780. PMID 3838797.
- Valerio D, Duyvesteyn MG, Dekker BM, et al. (1985). "Adenosine deaminase: characterization and expression of a gene with a remarkable promoter". EMBO J. 4 (2): 437–43. PMC 554205. PMID 3839456.
- Bonthron DT, Markham AF, Ginsburg D, Orkin SH (1985). "Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficiency". J. Clin. Invest. 76 (2): 894–7. doi:10.1172/JCI112050. PMC 423929. PMID 3839802.
- Daddona PE, Shewach DS, Kelley WN, et al. (1984). "Human adenosine deaminase. cDNA and complete primary amino acid sequence". J. Biol. Chem. 259 (19): 12101–6. PMID 6090454.
- Valerio D, Duyvesteyn MG, Meera Khan P, et al. (1984). "Isolation of cDNA clones for human adenosine deaminase". Gene 25 (2-3): 231–40. doi:10.1016/0378-1119(83)90227-5. PMID 6198240.
- ADA human gene location in the UCSC Genome Browser.
- ADA 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.
Adenosine-deaminase (editase) domain Provide feedback
Adenosine deaminases acting on RNA (ADARs) can deaminate adenosine to form inosine. In long double-stranded RNA, this process is non-specific; it occurs site-specifically in RNA transcripts. The former is important in defence against viruses, whereas the latter may affect splicing or untranslated regions. They are primarily nuclear proteins, but a longer isoform of ADAR1 is found predominantly in the cytoplasm. ADARs are derived from the Tad1-like tRNA deaminases that are present across eukaryotes. These in turn belong to the nucleotide/nucleic acid deaminase superfamily and are characterized by a distinct insert between the two conserved cysteines that are involved in binding zinc .
Iyer LM, Zhang D, Rogozin IB, Aravind L;, Nucleic Acids Res. 2011; [Epub ahead of print]: Evolution of the deaminase fold and multiple origins of eukaryotic editing and mutagenic nucleic acid deaminases from bacterial toxin systems. PUBMED:21890906 EPMC:21890906
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR002466Editase (EC) are enzymes that alter mRNA by catalyzing the site-selective deamination of adenosine residue into inosine residue. The editase domain contains the active site and binds three Zn atoms [PUBMED:9159072]. Several editases share a common global arrangement of domains, from N to C terminus: two 'double-stranded RNA-specific adenosine deaminase' (DRADA) repeat domains (INTERPRO), followed by three 'double-stranded RNA binding' (DsRBD) domains (INTERPRO), followed by the editase domain. Other editases have a simplified domains structure with no DRADA_REP and possibly fewer DSRBD domains. Editase that deaminate cytidine are not detected by this signature.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||RNA binding (GO:0003723)|
|adenosine deaminase activity (GO:0004000)|
|Biological process||RNA processing (GO:0006396)|
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...
This clan contains both free nucleotide and nucleic acid deaminases that act on adenosine, cytosine, guanine and cytidine, and are collectively known as the deaminase superfamily. The conserved fold consists of a three-layered alpha/beta/alpha structure with 3 helices and 4 strands in the 2134 order [1,2].This superfamily is further divided into two major divisions based on the presence of a helix (helix-4) that renders the terminal strands (strands 4 and 5) either parallel to each other in its presence, or anti-parallel in its absence . Structurally, the deaminase-like fold is present in four other superfamilies including the JAB-like metalloproteins, the C-terminal AICAR transformylase-catalyzing domains of PurH, Tm1506 and the formate dehydrogenase accessory subunit FdhD. The active site of the deaminases is composed of three residues that coordinate a zinc ion between conserved helices 2 and 3. The residues are typically found as [HCD]xE and CxxC motifs at the beginning of helices 2 and 3. The zinc ion activates a water molecule, which forms a tetrahderal intermediate with the carbon atom that is linked to the amine group. This is followed by deamination of the base.
The clan contains the following 16 members:A_deamin AICARFT_IMPCHas APOBEC_C APOBEC_N Bd3614-deam dCMP_cyt_deam_1 dCMP_cyt_deam_2 DYW_deaminase LmjF365940-deam MafB19-deam OTT_1508_deam Pput2613-deam SCP1201-deam Toxin-deaminase XOO_2897-deam YwqJ-deaminase
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.
|Author:||Mian N, Bateman A, Iyer LM, Zhang D, Aravind L|
|Number in seed:||59|
|Number in full:||781|
|Average length of the domain:||308.00 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||55.17 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null --hand HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||13|
|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 A_deamin domain has been found. There are 2 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...