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Lipoxygenase Edit Wikipedia article
Structure of rabbit reticulocyte 15S-lipoxygenase.
Lipoxygenases (EC 1.13.11.-) are a family of iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene structure as shown in the following reaction:
- Fatty acid + O2 = fatty acid hydroperoxide
The lipoxygenases are related to each other based upon their similar genetic structure and dioxygenation activity. However, one lipoxygenase, ALOXE3, while having a lipoxygenase genetic structure, possesses relatively little dioxygenation activity; rather its primary activity appears to be as an isomerase that catalyzes the conversion of hydroperoxy unsaturated fatty acids to their 1,5-epoxide,hydroxyl derivatives.
Lipoxygenases are found in plants, animals and fungi. Products of lipoxygenases are involved in diverse cell functions.
Biological function and classification
These enzymes are most common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of eicosanoids (such as prostaglandins, leukotrienes and nonclassic eicosanoids). Sequence data is available for the following lipoxygenases:
With the exception of the 5-LOX gene which is located on chromosome 10q11.2, all six human LOX genes are located on chromosome 17.p13 and code for a single chain protein of 75–81 kiloDaltons and consisting of 662–711 amino acids. Mammalian LOX genes contain 14 (ALOX5, ALOX12, ALOX15, ALOX15B) or 15 (ALOX12B, ALOXE3) exons with exon/intron boundaries at highly conserved position. The 6 human lipoxygenases along with some of the major products that they make as well as some their associations with genetic diseases are as follows:
- Arachidonate 5-lipoxygenase (ALOX5) (EC 220.127.116.11InterPro: IPR001885), also termed 5-lipoxygenase, 5-LOX, and 5-LO. Major products: it metabolizes arachidonic acid to 5-hydroperoxy-eicostetraeoic acid (5-HpETE) which is converted to 1) 5-Hydroxyicosatetraenoic acid (5-HETE) and then to 5-oxo-eicosatetraenoic acid (5-oxo-ETE) or 2) leukotriene A4 (LTBA) which may then be converted to leukotriene B4 (LTB4) or Leukotriene C4 (LTC4). LTC4 may be further metabolized to leukotriene D4 (LTD4) and then to Leukotriene E4 (LTE4).
- Arachidonate 12-lipoxygenase (ALOX12) (EC 18.104.22.168InterPro: IPR001885), also termed 12-lipoxygenase, platelet type platelet lipoxygenase (or 12-lipoxygenase, platelet type) 12-LOX, and 12-LO. It metabolizes arachidonic acid to 12-hydroperoxyeiocsatetraeoic acid (12-HpETE) which is further metabolized to 12-hydroxyeicosatetraenoic acid (12-HETE) or to various Hepoxilins (also see 12-hydroxyeicosatetraenoic acid).
- Arachidonate 15-lipoxygenase-1 (ALOX15) (EC 22.214.171.124InterPro: IPR001885), also termed 15-lipoxygenase-1, erythrocyte type 15-lipoxygenase (or 15-lipoxygenase, erythrocyte type), reticulocyte type 15-lipoxygenase (or 15-lipoxygenase, reticulocyte type), 15-LO-1, and 15-LOX-1. It metabolizes arachidonic acid principally to 1) 15-hydroperoxyeiocatetraenoic acid (15-HpETE) which is further metabolized to 15-Hydroxyicosatetraenoic acid (15-HETE) but also to far smaller amounts of 2) 12-hydroperoxyeicosatetraenoic acid (12-HpETE) which is further metabolized to 12-hydroxyeicosatetraenoic acid and possibly the hepoxilins. ALOX15 actually prefers linoleic acid over arachidonic acid, metabolizing linoleic acid to 12-hydroperoxyoctadecaenoic acid (13-HpODE) which is further metabolized to 13-Hydroxyoctadecadienoic acid (13-HODE). ALOX15 can metabolize polyunsaturated fatty acids that are esterified to phospholipids and/or to the cholesterol, i.e. cholesterol esters, in lipoproteins. This property along with is dual specificity in metabolizing arachidonic acid to 12-HpETE and 15-HpETE are similar to those of mouse Alox15 and has led to both enzymes being termed 12/15-lipoxygenases.
- Arachidonate 15-lipoxygenase type II (ALOX15B), also termed 15-lipoxygenase-2, 15-LOX-2, and 15-LOX-2. It metabolizes arachidonic acid to 15-hydroperoxyeicosatetraenoic (15-HpETE) which is further metabolized to 15-Hydroxyicosatetraenoic acid. ALOX15B has little or no ability to metabolize arachidonic acid to 12-hdroperoxeiocosatetraenoic acid (12-(HpETE) and only minimal ability to metabolize linoleic acid to 13-hydroperoxyoctadecaenoic acid (13-HpODE).
- Arachidonate 12-lipoxygenase, 12R type (ALOX12B), also termed 12R-lipoxygenase, 12R-LOX, and 12R-LO. It metabolizes arachidonic acid to 12R-hydroxyeicosatetraenoic acid but does so only with low catalytic activity; its most physiologically important substrate is thought to be a sphingosine which contains a very long chain (16-34 carbons) omega-hydroxyl fatty acid that is in amide linkage to the sn-2 nitrogen of sphingosine at its carboxy end and esterfied to linoleic acid at its omega hydroxyl end. In skin epidermal cells, ALOX12B metabolizes the linoleate in this esterified omega-hydroxyacyl-sphingosine (EOS) to its 9R-hydroperoxy analog. Inactivating mutations of ALOX12B are associated with the human skin disease, autosomal recessive Congenital ichthyosiform erythroderma (ARCI).
- Epidermis-type lipoxygenase (ALOXE3), also termed eLOX3 and lipoxygenase, epidermis type. Unlike other lipoxygenases, ALOXE3 exhibits only a latent dioxygenase activity. Rather, its primary activity is as a hydroperoxide isomerase that metabolizes certain unsaturated hydroperoxy fatty acids to their corresponding epoxy alcohol and epoxy keto derivatives and thereby is also classified as a hepoxilin synthase. While it can metabolize 12S-hydroperoxyeicosatetraenoic acid (12S-HpETE) to the R stereoisomers of hepoxilins A3 and B3, ALOXE3 favors metabolizing R hydroperoxy unsaturated fatty acids and efficiently converts the 9(R)-hydroperoxy analog of EOS made by ALOX15B to its 9R(10R),13R-trans-epoxy-11E,13R and 9-keto-10E,12Z EOS analogs. ALOX3 is thought to act with ALOX12B in skin epidermis to form the latter two EOS analogs; inactivation mutations of ALOX3 are, similar to inactivating mutations in ALOX12B, associated with autosomal recessive Congenital ichthyosiform erythroderma in humans. Inactivating mutations in ALOX3 are also associated with the human disease Lamellar ichthyosis, type 5 (see Ichthyosis#Types#Genetic disease with ichthyosis).
Two lipoxygenases may act in series to make di-hydroxy or tri-hydroxy products that have activities quite different than either lipoxyenases' products. This serial metabolism may occur in different cell types that express only one of the two lipoxygenases in a process termed transcellular metabolism. For example, ALOX5 and ALOX15 or, alternatively, ALOX5 and ALOX12 can act serially to metabolize arachidonic acid into lipoxins (see 15-hydroxyicosatetraenoic acid#Further metabolism of 15(S)-HpETE, 15(S)-HETE, 15(R)-HpETE, 15(R)-HETE, and 15-oxo-ETE and lipoxin#Biosynthesis) while ALOX15 and possibly ALOX15B can act with ALOX5 to metabolize eicosapentaenoic acid to resolvin D's (see resolvin#Production).
The mouse is a common model to examine lipoxygenase function. However, there are some key differences between the lipoxygenases between mice and men that make extrapolations from mice studies to humans difficult. In contrast to the 6 functional lipoxygenases in humans, mice have 7 functional lipoxygenases and some of the latter have different metabolic activities than their human orthologs. In particular, mouse Alox15, unlike human ALOX15, metabolizes arachidonic acid mainly to 12-HpETE and mouse Alox15b, in contrast to human ALOX15b, is primarily an 8-lipoxygenase, metabolizing arachdionic acid to 8-HpETE; there is no comparable 8-HpETE-forming lipoxygenase in humans.
- Alox5 appears to be similar in function to human ALOX5.
- Alox12 differs from human ALOX12, which preferentially metabolizes arachidonic acid to 12-HpETE but also to substantial amounts of 15-HpETE, in that metabolizes arachidonic acid almost exclusively to 12-HpETE.
- Alox15 (also termed leukocyte-type 12-Lox, 12-Lox-l, and 12/15-Lox) differs from human ALOX15, which under standard assay conditions metabolizes arachidonic acid to 15-HpETE and 12-HpETE products in an 89 to 11 ratio, metabolizes arachidconic acid to 15-Hpete and 12-HpETE in a 1 to 6 ratio, i.e. its principal metabolite is 12-HpETE. Also, human ALOX15 prefers linoleic acid over arachidonic acid as a substrate, metabolizing it to 13-HpODE while Alox15 has little or no activity on linoleic acid. Alox15 can metabolize polyunsaturated fatty acids that are esterified to phospholipids and cholesterol (i.e. cholesterol esters). This property along with is dual specificity in metabolizing arachidonic acid to 12-HpETE and 15-HpETE are similar to those of human ALOX15 and has led to both enzymes being termed 12/15-lipoxygenases.
- Alox15b (also termed 8-lipoxygenase, 8-lox, and 15-lipoxygenase type II), in contrast to ALOX15B which metabolizes arachidonic acid principally to 15-HpETE and to a lesser extent linoleic acid to 13-HpODE, metabolizes arachidonic acid principally to 8S-HpETE and linoleic acid to 9-HpODE. Alox15b is as effective as ALOX5 in metabolizing 5-HpETE to leukotrienes.
- Alox12e (12-Lox-e, epidermal-type 12-Lox) is an ortholog to the human ALOX12P gene which has suffered damaging mutations and is not expressed. ALox12e prefers methyl esters over non-esterfied polyunsaturated fatty acid substrates, metabolizing linoleic acid ester to its 13-hydroperoxy counterpart and to a lesser extent arachidonic acid ester to its 12-hydroperoxy counterpart.
- Alox12b (e-LOX2, epidermis-type Lox-12) appears to act similarly to ALOX12B to metabolize the linoleic acid moiety of EOS to its 9R-hydroperoxy counterpart and thereby contribute to skin integrity and water impermeability; mice depleted to Alox12b develop a severe skin defect similar to Congenital ichthyosiform erythroderma. Unlike human ALOX12B which cam metabolize arachidonic acid to 12R-HETE at a low rate, Alox12b does not metabolize arachidonic acid as free acd but dose metabolize arachidonic acid methyl ester to its 12R-hydroperoxy counterpart.
- Aloxe3 (epidermis-type Lox-3, eLox3) appears to act similarly to ALOXe3 in metabolizing the 9R-hydoperoxy-linoleate derivative of EOS to its epoxy and keto derivatives and to be involved in maintaining skin integrity and water impermeability. AloxE3 deletion leads to a defect similar to congenital ichthyosiform erythroderma.
There are several lipoxygenase structures known including: soybean lipoxygenase L1 and L3, coral 8-lipoxygenase, human 5-lipoxygenase, rabbit 15-lipoxygenase and porcine leukocyte 12-lipoxygenase catalytic domain. The protein consists of a small N-terminal PLAT domain and a major C-terminal catalytic domain (see Pfam link in this article), which contains the active site. In both plant and mammalian enzymes, the N-terminal domain contains an eight-stranded antiparallel β-barrel, but in the soybean lipoxygenases this domain is significantly larger than in the rabbit enzyme. The plant lipoxygenases can be enzymatically cleaved into two fragments which stay tightly associated while the enzyme remains active; separation of the two domains leads to loss of catalytic activity. The C-terminal (catalytic) domain consists of 18-22 helices and one (in rabbit enzyme) or two (in soybean enzymes) antiparallel β-sheets at the opposite end from the N-terminal β-barrel.
The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three zinc-ligands; the other histidines have been shown to be important for the activity of lipoxygenases.
The two long central helices cross at the active site; both helices include internal stretches of π-helix that provide three histidine (His) ligands to the active site iron. Two cavities in the major domain of soybean lipoxygenase-1 (cavities I and II) extend from the surface to the active site. The funnel-shaped cavity I may function as a dioxygen channel; the long narrow cavity II is presumably a substrate pocket. The more compact mammalian enzyme contains only one boot-shaped cavity (cavity II). In soybean lipoxygenase-3 there is a third cavity which runs from the iron site to the interface of the β-barrel and catalytic domains. Cavity III, the iron site and cavity II form a continuous passage throughout the protein molecule.
The active site iron is coordinated by Nε of three conserved His residues and one oxygen of the C-terminal carboxyl group. In addition, in soybean enzymes the side chain oxygen of asparagine is weakly associated with the iron. In rabbit lipoxygenase, this Asn residue is replaced with His which coordinates the iron via Nδ atom. Thus, the coordination number of iron is either five or six, with a hydroxyl or water ligand to a hexacoordinate iron.
Details about the active site feature of lipoxygenase were revealed in the structure of porcine leukocyte 12-lipoxygenase catalytic domain complex  In the 3D structure, the substrate analog inhibitor occupied a U-shaped channel open adjacent to the iron site. This channel could accommodate arachidonic acid without much computation, defining the substrate binding details for the lipoxygenase reaction. In addition, a plausible access channel, which intercepts the substrate binding channel and extended to the protein surface could be counted for the oxygen path.
|EC 126.96.36.199||lipoxygenase||(linoleate:oxygen 13-oxidoreductase)||linoleate + O2 = (9Z,11E,13S)-13-hydroperoxyoctadeca-9,11-dienoate|
|EC 188.8.131.52||arachidonate 12-lipoxygenase||(arachidonate:oxygen 12-oxidoreductase)||arachidonate + O2 = (5Z,8Z,10E,12S,14Z)-12-hydroperoxyicosa-5,8,10,14-tetraenoate|
|EC 184.108.40.206||arachidonate 15-lipoxygenase||(arachidonate:oxygen 15-oxidoreductase)||arachidonate + O2 = (5Z,8Z,11Z,13E,15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate|
|EC 220.127.116.11||arachidonate 5-lipoxygenase||(arachidonate:oxygen 5-oxidoreductase)||arachidonate + O2 = leukotriene A4 + H2|
|EC 18.104.22.168||arachidonate 8-lipoxygenase||(arachidonate:oxygen 8-oxidoreductase)||arachidonate + O2 = (5Z,8R,9E,11Z,14Z)-8-hydroperoxyicosa-5,9,11,14-tetraenoate|
Soybean Lipoxygenase 1 exhibits the largest H/D kinetic isotope effect (KIE) on kcat (kH/kD) (81 near room temperature) so far reported for a biological system. Recently, an extremely elevated KIE of 540 to 730 was found in a double mutant Soybean Lipoxygenase 1. Because of the large magnitude of the KIE, Soybean Lipoxygenase 1 has served as the prototype for enzyme-catalyzed hydrogen-tunneling reactions.
Human proteins expressed from the lipoxygenase family include ALOX12, ALOX12B, ALOX15, ALOX15B, ALOX5, and ALOXE3. While humans also possess the ALOX12P2 gene, which is an ortholog of the well-expressed Alox12P gene in mice, the human gene is a pseudogene; consequently, ALOX12P2 protein is not detected in humans.
- Choi J, Chon JK, Kim S, Shin W (February 2008). "Conformational flexibility in mammalian 15S-lipoxygenase: Reinterpretation of the crystallographic data". Proteins 70 (3): 1023–32. doi:10.1002/prot.21590. PMID 17847087.
- Vick BA, Zimmerman DC (1987). "Oxidative systems for the modification of fatty acids: The Lipoxygenase Pathway" 9: 53–90. doi:10.1016/b978-0-12-675409-4.50009-5. ISBN 9780126754094.
- Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB (1986). "Arachidonic acid metabolism". Annu. Rev. Biochem. 55: 69–102. doi:10.1146/annurev.bi.55.070186.000441. PMID 3017195.
- Tanaka K, Ohta H, Peng YL, Shirano Y, Hibino T, Shibata D (1994). "A novel lipoxygenase from rice. Primary structure and specific expression upon incompatible infection with rice blast fungus". J. Biol. Chem. 269 (5): 3755–3761. PMID 7508918.
- Krieg, P; Fürstenberger, G (2014). "The role of lipoxygenases in epidermis". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1841 (3): 390–400. doi:10.1016/j.bbalip.2013.08.005. PMID 23954555.
- Haeggström, J. Z.; Funk, C. D. (2011). "Lipoxygenase and leukotriene pathways: Biochemistry, biology, and roles in disease". Chemical Reviews 111 (10): 5866–98. doi:10.1021/cr200246d. PMID 21936577.
- Muñoz-Garcia, A; Thomas, C. P.; Keeney, D. S.; Zheng, Y; Brash, A. R. (2014). "The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1841 (3): 401–8. doi:10.1016/j.bbalip.2013.08.020. PMC 4116325. PMID 24021977.
- Taylor, P. R.; Heydeck, D; Jones, G. W.; Krönke, G; Funk, C. D.; Knapper, S; Adams, D; Kühn, H; O'Donnell, V. B. (2012). "Development of myeloproliferative disease in 12/15-lipoxygenase deficiency". Blood 119 (25): 6173–4; author reply 6174–5. doi:10.1182/blood-2012-02-410928. PMC 3392071. PMID 22730527.
- Cole, B. K.; Lieb, D. C.; Dobrian, A. D.; Nadler, J. L. (2013). "12- and 15-lipoxygenases in adipose tissue inflammation". Prostaglandins & Other Lipid Mediators. 104-105: 84–92. doi:10.1016/j.prostaglandins.2012.07.004. PMC 3526691. PMID 22951339.
- Boyington JC, Gaffney BJ, Amzel LM (1993). "The three-dimensional structure of an arachidonic acid 15-lipoxygenase". Science 260 (5113): 1482–1486. doi:10.1126/science.8502991. PMID 8502991.
- Steczko J, Donoho GP, Clemens JC, Dixon JE, Axelrod B (1992). "Conserved histidine residues in soybean lipoxygenase: functional consequences of their replacement". Biochemistry 31 (16): 4053–4057. doi:10.1021/bi00131a022. PMID 1567851.
- Xu, S.; Mueser T.C.; Marnett L.J.; Funk M.O. (2012). "Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis.". Structure 20 (9): 1490–7. doi:10.1016/j.str.2012.06.003. PMID 22795085.
- Hu, S; Sharma, S. C.; Scouras, A. D.; Soudackov, A. V.; Carr, C. A.; Hammes-Schiffer, S; Alber, T; Klinman, J. P. (2014). "Extremely elevated room-temperature kinetic isotope effects quantify the critical role of barrier width in enzymatic C-H activation". Journal of the American Chemical Society 136 (23): 8157–60. doi:10.1021/ja502726s. PMC 4188422. PMID 24884374.
- LOX-DB - LipOXygenases DataBase
- Lipoxygenases iron-binding region in PROSITE
- - structure of lipoxygenase-1 from soybean (Glycine max)
- - structure of soybean lipoxygenase-3 in complex with (9Z,11E,13S)-13-hydroperoxyoctadeca-9,11-dienoic acid
- - structure of rabbit 15-lipoxygenase in complex with inhibitor
- - structure of the catalytic domain of porcine leukocyte 12-lipoxygenasean with inhibitor
- UMich Orientation of Proteins in Membranes families/superfamily-87 - animal lipoxygenases
- Lipoxygenase at the US National Library of Medicine Medical Subject Headings (MeSH)
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.
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InterPro entry IPR013819
Lipoxygenases (EC) are a class of iron-containing dioxygenases which catalyses the hydroperoxidation of lipids, containing a cis,cis-1,4-pentadiene structure. They are common in plants where they may be involved in a number of diverse aspects of plant physiology including growth and development, pest resistance, and senescence or responses to wounding. In mammals a number of lipoxygenases isozymes are involved in the metabolism of prostaglandins and leukotrienes [PUBMED:3017195]. Sequence data is available for the following lipoxygenases:
- Plant lipoxygenases (EC). Plants express a variety of cytosolic isozymes as well as what seems to be a chloroplast isozyme [PUBMED:7508918].
- Mammalian arachidonate 5-lipoxygenase (EC).
- Mammalian arachidonate 12-lipoxygenase (EC).
- Mammalian erythroid cell-specific 15-lipoxygenase (EC).
The iron atom in lipoxygenases is bound by four ligands, three of which are histidine residues [PUBMED:8502991]. Six histidines are conserved in all lipoxygenase sequences, five of them are found clustered in a stretch of 40 amino acids. This region contains two of the three iron-ligands; the other histidines have been shown [PUBMED:1567851] to be important for the activity of lipoxygenases.
This entry represents the C-terminal region of these proteins.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702)|
|metal ion binding (GO:0046872)|
|Biological process||oxidation-reduction process (GO:0055114)|
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|Number in seed:||117|
|Number in full:||2073|
|Average length of the domain:||423.90 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||69.41 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||17|
|Download:||download the raw HMM for this family|
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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 are 3 interactions 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 Lipoxygenase domain has been found. There are 77 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...