Summary: Heme oxygenase
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 "Heme oxygenase". 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.
Heme oxygenase Edit Wikipedia article
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / QuickGO|
Crystal structures of ferrous and ferrous-no forms of verdoheme in a complex with human heme oxygenase-1: catalytic implications for heme cleavage
|SCOPe||1qq8 / SUPFAM|
Heme oxygenase or haem oxygenase (HO) is an enzyme that catalyzes the degradation of heme. This produces biliverdin, ferrous iron, and carbon monoxide. HO was first described in the late 1960's when Tenhunen demonstrated an enzymatic reaction for heme catabolism. HO is the premier source for endogenous carbon monoxide (CO) production. Indeed, monitored small doses of CO are being studied for therapeutic benefits.
Heme oxygenase is a heme-containing member of the heat shock protein (HSP) family identified as HSP32. HO-1 is a 32kDa enzyme contains 288 amino acid residues. HO is located in the endoplasmic reticulum, though it has also been reported in the mitochondria, cell nucleus, and plasma membrane.
HO catalyzes the degradation of heme to biliverdin/bilirubin, ferrous iron, and carbon monoxide. Though present throughout the body, HO has significant activity in the spleen in the degradation of hemoglobin during erythrocyte recycling (0.8% of the erythrocyte pool per day), which accounts for ~80% of the heme derived endogenous CO production. The remaining 20% of heme derived CO production is largely attributed to hepatic catabolism of hemoproteins (myoglobin, cytochromes, catalase, peroxidases, soluble guanylate cyclase, nitric oxide synthase) and ineffective erythropoiesis in bone marrow. HO enzymes are degraded via ubiquitination. In humans three isoforms of heme oxygenase are known.
Heme oxygenase 1
Heme oxygenase 1 (HO-1) is a stress-induced isoform present throughout the body with highest concentrations in the spleen, liver, and kidneys. HO-1 is a 32kDa enzyme containing 288 amino acid residues which is encoded by the HMOX1 gene. A study has found levels of HO-1 in lung tissue were directly related to infection with Tuberculosis or infection-free areas, and knockout mice were found susceptible, showing the essential role of this enzyme.
Heme oxygenase 2
Heme oxygenase 2 (HO-2) is a constitutive isoform that is expressed under homeostatic conditions in the testes, endothelial cells and the brain. HO-2 is encoded by the HMOX2 gene. HO-2 is 36 kDa and shares 47% similarity with the HO-1 amino acid sequence.
Heme oxygenase 3
A third heme oxygenase (HO-3) is considered to be catalytically inactive and is thought to work in heme sensing or heme binding. HO-3 is 33 kDa with greatest presence in the liver, prostate, and kidneys.
Microbial heme oxygenase
Heme oxygenase is conserved across phylogenic kingdoms. The European Bioinformatics Instituteâ€™s InterPro taxonomy database indicates there are 4,347 bacteria species, 552 fungi species, and 6 archaea species expressing a HO-1-like enzymes. Microbial HO homologues use different abbreviation such as HMX1 in Saccharomyces cerevisiae, Hmu O in Corynebacterium diphtheriae, and Chu S in Escherichia coli. A critical role of the prokaryotic HO systems is to facilitate acquisition of nutritional iron from a eukaryotic host. Some HO-like prokaryotic enzymes are inactive or do not liberate CO. Certain strains of Escherichia coli express the non-CO producing Chu W isoform, whilst HO-like enzymes in other microbes have been reported to produce formaldehyde.
Heme oxygenase cleaves the heme ring at the alpha-methene bridge to form either biliverdin or, if the heme is still attached to a globin, verdoglobin. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. The reaction comprises three steps, which may be:
- Heme b3+ + O
2 + NADPH + H+
â†’ Î±-meso-hydroxyheme3+ + NADP+
- Î±-meso-hydroxyheme3+ + H+
2 â†’ verdoheme4+ + CO + H2O
- verdoheme4+ + 7/2 NADPH + O
2+ 3/2 H+
â†’ biliverdin + Fe2+ + 7/2 NADP+
- Heme b3+ + O
The sum of these reactions is:
- Heme b3+ + 3O
2 + 9/2 NADPH + 7/2 H+
â†’ biliverdin + Fe2+ + CO + 9/2 NADP+
If the iron is initially in the +2 state, the reaction could be:
- Heme b2+ + 3O2 + 4 NADPH + 4 H+ â†’ biliverdin + Fe2+ + CO + 4 NADP+ + 3H2O
This reaction can occur in virtually every cell; the classic example is the formation of a contusion, which forms different chromogens as it gradually heals: (red) heme to (green) biliverdin to (yellow) bilirubin. In terms of molecular mechanisms, the enzyme facilitates the intramolecular hydroxylation of one meso carbon centre in the heme.
HO-1 is induced by countless molecules including heavy metals, statins, paclitaxel, rapamycin, probucol, nitric oxide, sildenafil, carbon monoxide, carbon monoxide-releasing molecules, and porphyrins.
Phytochemical inducers of HO include: curcumin, resveratrol, piceatannol, caffeic acid phenethyl ester, dimethyl fumarate, fumaric acid esters, flavonoids, chalcones, ginkgo biloba, anthrocyanins, phlorotannins, carnosol, rosolic acid, and numerous other natural products.
NRF2 inducers with downstream HO-1 induction include: genistein, 3-hydroxycoumarin, oleanolic acid, isoliquiritigenin, PEITC, diallyl trisulfide, oltipraz, benfotiamine, auranofin, acetaminophen, nimesulide, paraquat, ethoxyquin, diesel exhaust particles, silica, nanotubes, 15â€deoxyâ€Î”12,14 prostaglandin J2, nitro-oleic acid, hydrogen peroxide, and succinylacetone.
Roles in physiology
Heme oxygenase expression is induced by oxidative stress, and in animal models increasing this expression seems to be protective. Carbon monoxide released from heme oxygenase reactions can influence vascular tone independently or influence the function of nitric oxide synthase.
Endogenous carbon monoxide
- See also: carbon monoxide-releasing molecules
The first detection of CO in humans was in 1949. SjÃ¶strand determined that CO originated from the alpha-methene carbon of heme, setting the stage for the molar ratio between hemin degradation and CO production to be established. HO is the main source of endogenous CO production, though other minor contributors have been identified in recent years. CO is formed at a rate of 16.4 Âµmol/hour in the human body, ~86% originating from heme via heme oxygenase and ~14% from non-heme sources including: photooxidation, lipid peroxidation, and xenobiotics. The average carboxyhemoglobin (CO-Hb) level in a non-smoker is between 0.2% and 0.85% CO-Hb (whereas a smoker may have between 4% and 10% CO-Hb), though geographic location, occupation, health and behavior are contributing variables. Among these, the microbial HO system within the digestive tract is believed to contribute to systemic CO-Hb concentrations.
- Kikuchi G, Yoshida T, Noguchi M (2005). "Heme oxygenase and heme degradation". Biochem. Biophys. Res. Commun. 338 (1): 558â€“567. doi:10.1016/j.bbrc.2005.08.020. PMID 16115609.
- Ryter SW, Alam J, Choi AM (2006). "Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications". Physiological Reviews. 86 (2): 583â€“650. doi:10.1152/physrev.00011.2005. PMID 16601269.
- Tenhunen R, Marver HS, Schmid R (1969). "Microsomal heme oxygenase. Characterization of the enzyme". The Journal of Biological Chemistry. 244 (23): 6388â€“6394. PMID 4390967.
- Motterlini R, Otterbein LE (2010). "The therapeutic potential of carbon monoxide". Nature Reviews. Drug Discovery. 9 (9): 728â€“743. doi:10.1038/nrd3228. PMID 20811383.
- Barton SG, Rampton DS, Winrow VR, Domizio P, Feakins RM (2003). "Expression of heat shock protein 32 (hemoxygenase-1) in the normal and inflamed human stomach and colon: an immunohistochemical study". Cell Stress & Chaperones. 8 (4): 329â€“334. doi:10.1379/1466-1268(2003)008<0329:eohsph>2.0.co;2. PMC 514904. PMID 15115285.
- Hopper CP, Meinel L, Steiger C, Otterbein LE (2018). "Where is the Clinical Breakthrough of Heme Oxygenase-1 / Carbon Monoxide Therapeutics?". Current Pharmaceutical Design. 24 (20): 2264â€“2282. doi:10.2174/1381612824666180723161811. PMID 30039755.
- Breman HJ, Wong RJ, Stevenson DK (2001). "Chapter 15: Sources, Sinks, and Measurement of Carbon Monoxide". In Wang R (ed.). Carbon Monoxide and Cardiovascular Functions (2nd ed.). CRC Press. ISBN 978-0-8493-1041-6.
- Lin, P (2008). "Ubiquitinâ€“proteasome system mediates heme oxygenase-1 degradation through endoplasmic reticulum-associated degradation pathway". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1783 (10): 1826â€“1834. doi:10.1016/j.bbamcr.2008.05.008. PMID 18544348.
- Elbirt K, Bonkovsky H (1999). "Heme Oxygenase: Recent Advances in Understanding Its Regulation and Role". Proceedings of the Association of American Physicians. 111 (5): 438â€“447. doi:10.1111/paa.19126.96.36.1998.
- MuÃ±oz-SÃ¡nchez J, ChÃ¡nez-CÃ¡rdenas ME (2014). "A review on hemeoxygenase-2: focus on cellular protection and oxygen response". Oxidative Medicine and Cellular Longevity. 2014 (1): 1â€“16. doi:10.1155/2014/604981. PMC 4127239. PMID 25136403.
- Li C, Stocker R (2013). "Heme oxygenase and iron: from bacteria to humans". Redox Report. 14 (3): 95â€“101. doi:10.1179/135100009X392584. PMID 19490750.
- Protchenko O, Shakoury-Elizeh M, Keane P, Storey J, Androphy R, Philpott CC (2008). "Role of PUG1 in inducible porphyrin and heme transport in Saccharomyces cerevisiae". Eukaryotic Cell. 7 (5): 859â€“871. doi:10.1128/EC.00414-07. PMC 2394968. PMID 18326586.
- Wilks A, Schmitt MP (1998). "Expression and characterization of a heme oxygenase (Hmu O) from Corynebacterium diphtheriae. Iron acquisition requires oxidative cleavage of the heme macrocycle". The Journal of Biological Chemistry. 273 (2): 837â€“841. doi:10.1074/jbc.273.2.837. PMID 9422739.
- Maharshak N, Ryu HS, Fan TJ, Onyiah JC, Schulz S, Otterbein SL, Wong R, Hansen JJ, Otterbein LE, Carroll IM, Plevy SE (2015). "Escherichia coli heme oxygenase modulates host innate immune responses". Microbiology and Immunology. 59 (8): 452â€“465. doi:10.1111/1348-0421.12282. PMC 4582649. PMID 26146866.
- Frankenberg-Dinkel, Nicole (2004). "Bacterial Heme Oxygenases". Antioxidants & Redox Signaling. 6 (5): 825â€“834. doi:10.1089/ars.2004.6.825. PMID 15345142.
- LaMattina JW, Nix DB, Lanzilotta WN (2016). "Radical new paradigm for heme degradation in Escherichia coli O157:H7". Proceedings of the National Academy of Sciences of the United States of America. 113 (43): 12138â€“12143. doi:10.1073/pnas.1603209113. PMC 5087033. PMID 27791000.
- Matsui T, Nambu S, Ono Y, Goulding CW, Tsumoto K, Ikeda-Saito M (2013). "Heme degradation by Staphylococcus aureus IsdG and IsdI liberates formaldehyde rather than carbon monoxide". Biochemistry. 52 (18): 3025â€“3027. doi:10.1021/bi400382p. PMC 3672231. PMID 23600533.
- Wang R, ed. (2001). Carbon Monoxide and Cardiovascular Functions. CRC Press. p. 5. ISBN 978-1-4200-4101-9.
- Evans JP, Niemevz F, Buldain G, de Montellano PO (2008). "Isoporphyrin intermediate in heme oxygenase catalysis. Oxidation of alpha-meso-phenylheme". J. Biol. Chem. 283 (28): 19530â€“19539. doi:10.1074/jbc.M709685200. PMC 2443647. PMID 18487208. The reference does not give the exact stoichiometry of each reaction.
- Yoshida T, Taiko Migita C (2000). "Focused Review Mechanism of heme degradation by heme oxygenase". Journal of Inorganic Biochemistry. 82 (1â€“4): 33â€“41. doi:10.1016/S0162-0134(00)00156-2. PMID 11132636.
- FerrÃ¡ndiz ML, Devesa I (2008). "Inducers of heme oxygenase-1". review. Current Pharmaceutical Design. 14 (5): 473â€“86. doi:10.2174/138161208783597399. PMID 18289074.
- Correa-Costa M, Otterbein LE (2014). "Eat to Heal: Natural Inducers of the Heme Oxygenase-1 System.". In Folkerts G, Garssen J (eds.). Pharma-Nutrition. secondary. AAPS Advances in the Pharmaceutical Sciences Series. 12. Springer, Cham. pp. 243â€“256. doi:10.1007/978-3-319-06151-1_12. ISBN 978-3-319-06150-4.
- Ma Q, He X (2012). "Molecular basis of electrophilic and oxidative defense: promises and perils of Nrf2". Pharmacol. Rev. 64 (4): 1055â€“1081. doi:10.1124/pr.110.004333. PMC 4648289. PMID 22966037.
- SjÃ¶strand T (1949). "Endogenous formation of carbon monoxide in man under normal and pathological conditions". Scandinavian Journal of Clinical and Laboratory Investigation. 1 (3): 201â€“214. doi:10.3109/00365514909069943.
- SjÃ¶strand T (1952). "The in vitro formation of carbon monoxide in blood". Acta Physiologica Scandinavica. 24 (4): 314â€“332. doi:10.1111/j.1748-1716.1952.tb00848.x. PMID 14952314.
- Coburn RF (1973). "Endogenous carbon monoxide metabolism". Annual Review of Medicine. 24: 241â€“250. doi:10.1146/annurev.me.24.020173.001325. PMID 4575855.
- Thom SR (2008). "Chapter 15: Carbon monoxide pathophysiology and treatment". In Neuman TS, Thom SR (eds.). Physiology and medicine of hyperbaric oxygen therapy. pp. 321â€“347. doi:10.1016/B978-1-4160-3406-3.50020-2. ISBN 9781416034063.
- Oleskin AV, Shenderov BA (2016). "Neuromodulatory effects and targets of the SCFAs and gasotransmitters produced by the human symbiotic microbiota". Microb. Ecol. Health Dis. 27: 30971. doi:10.3402/mehd.v27.30971. PMC 4937721. PMID 27389418.
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.
Heme oxygenase Provide feedback
No Pfam abstract.
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR016053
Haem oxygenase (EC) (HO) [PUBMED:3290025] is the microsomal enzyme that, in animals, carries out the oxidation of haem, it cleaves the haem ring at the alpha-methene bridge to form biliverdin and carbon monoxide [PUBMED:3032976]. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. In mammals there are three isozymes of haem oxygenase: HO-1 to HO-3. The first two isozymes differ in their tissue expression and their inducibility: HO-1 is highly inducible by its substrate haem and by various non-haem substances, while HO-2 is non-inducible. It has been suggested [PUBMED:8093563] that HO-2 could be implicated in the production of carbon monoxide in the brain where it is said to act as a neurotransmitter. In the genome of the chloroplast of red algae as well as in cyanobacteria, there is a haem oxygenase (gene pbsA) that is the key enzyme in the synthesis of the chromophoric part of the photosynthetic antennae [PUBMED:9326680]. A haem oxygenase is also present in the bacteria Corynebacterium diphtheriae (gene hmuO), where it is involved in the acquisition of iron from the host haem [PUBMED:9006041]. There is, in the central section of these enzymes, a well-conserved region centred on a histidine residue.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||heme oxygenase (decyclizing) activity (GO:0004392)|
|Biological process||heme oxidation (GO:0006788)|
|oxidation-reduction process (GO:0055114)|
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 includes the Heme oxygenase family as well as the TENA/THI-4/PQQC family that are less well characterised .
The clan contains the following 5 members:DUF3050 DUF3865 Haem_oxygenas_2 Heme_oxygenase TENA_THI-4
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:||Finn RD , Bateman A|
|Number in seed:||18|
|Number in full:||3231|
|Average length of the domain:||191.40 aa|
|Average identity of full alignment:||23 %|
|Average coverage of the sequence by the domain:||73.08 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||21|
|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 Heme_oxygenase domain has been found. There are 177 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...