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 "Lipoxygenase". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Lipoxygenase Edit Wikipedia article
Structure of rabbit reticulocyte 15S-lipoxygenase.
Lipoxygenases (EC 1.13.11.-) are a family of (non-heme), iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4- pentadiene into cell signaling agents that serve diverse roles as autocrine signals that regulate the function of their parent cells, paracrine signals that regulate the function of nearby cells, and endocrine signals that regulate the function of distant cells.
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 eukaryotes (plants, fungi, animals, protists); while the third domain of terrestrial life, the archaea, possesses proteins with a slight (~20%) amino acid sequence similarity to lipoxygenases, these proteins lack iron-binding residues and therefore are not projected to possess lipoxygenase activity.
Based on detailed analyses of 15-lipoxygenase 1 and stabilized 5-lipoxygenase, lipoxygenase structures consist of a 15 kilodalton N-terminal beta barrel domain, a small (e.g. ~0.6 kilodalton) linker inter-domain (see protein domain#Domains and protein flexibility), and a relatively large C-terminal catalytic domain which contains the non-heme iron critical for the enzymes' catalytic activity. Most of the lipoxygenases (exception, ALOXE3) catalyze the reaction Polyunsaturated fatty acid + O2 → fatty acid hydroperoxide in four steps:
- the rate-limiting step of hydrogen abstraction from a bisallylic methylene carbon to form a fatty acid radical at that carbon
- rearrangement of the radical to another carbon center
- addition of molecular oxygen (O2) to the rearranged carbon radical center thereby forming a peroxy radical(—OO·) bond to that carbon
- reduction of the peroxy radical to its corresponding anion (—OO−)
The (—OO−) residue may then be protonated to form a hydroperoxide group (—OOH) and further metabolized by the lipoxygenase to e.g. leukotrienes, hepoxilins, and various specialized pro-resolving mediators, or reduced by ubiquitous cellular glutathione peroxidases to a hydroxy group thereby forming hydroxylated (—OH) polyunsaturated fatty acids such as the Hydroxyeicosatetraenoic acids and HODEs (i.e. hydroxyoctadecaenoic acids).
Polyunsaturated fatty acids that serve as substrates for one or more of the lipoxygenases include the omega 6 fatty acids, arachidonic acid, linoleic acid, dihomo-γ-linolenic acid, and adrenic acid; the omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid; and the omega-9 fatty acid, mead acid. Certain types of the lipoxygenases, e.g. human and marine 15-lipoxygenase 1, 12-lipoxygenase B, and ALOXE3, are capable of metabolizing fatty acid substrates that are constituents of phospholipids, cholesterol esters, or complex lipids of the skin. Most lipoxygenases catalyze the formation of initially formed hydroperoxy products that have S chirality. Exceptions to this rule include the 12R-lipoxygenases of humans and other mammals (see below).
Lipoxygenases depend on the availability of their polyunsaturated fatty acid substrates which, particularly in mammalian cells, is normally maintained at extremely low levels. In general, various phospholipase A2s and diacylglycerol lipases are activated during cell stimulation, proceed to release these fatty acids from their storage sites, and thereby are key regulators in the formation of lipoxygenase-dependent metabolites. In addition, cells, when so activated, may transfer their released polyunsaturated fatty acids to adjacent or nearby cells which then metabolize them through their lipoxygenase pathways in a process termed transcellular metabolism or transcellular biosynthesis.
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:
Plants express a variety of cytosolic lipoxygenases (EC 126.96.36.199InterPro: IPR001246) as well as what seems to be a chloroplast isozyme. Plant lipoxygenase in conjunction with hydroperoxide lyases are responsible for many fragrances and other signalling compounds. One example is cis-3-hexenal, the odor of freshly cut grass.
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 188.8.131.52InterPro: 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), 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]), or 3 acting in series with ALOX15, to the Specialized pro-resolving mediators, lipoxins A4 and B4. ALOX5 also metabolizes eicosapentaenoic acid to a set of metabolites that contain 5 double bounds (i.e. 5-HEPE, 5-oxo-EPE, LTB5, LTC5, LTD5, and LTE5) as opposed to the 4 double bond-containing arachidonic acid metabolites. The enzyme, when acting in series with other lipoxygenase, cyclooxygenase, or cytochrome P450 enzymes, contributes to the metabolism of eicosapentaenoic acid to E series resolvins (see Resolvin#Resolvin Es) and of docosahexaenoic acid to D series resolvins (see Resolvin#Resolvin Ds). these resolvins are also classified as Specialized pro-resolving mediators.
- Arachidonate 12-lipoxygenase (ALOX12) (EC 184.108.40.206InterPro: 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 220.127.116.11InterPro: 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-hydroperoxeiocosatetraenoic 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. ALOXE3 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 18.104.22.168||lipoxygenase||(linoleate:oxygen 13-oxidoreductase)||linoleate + O2 = (9Z,11E,13S)-13-hydroperoxyoctadeca-9,11-dienoate|
|EC 22.214.171.124||arachidonate 12-lipoxygenase||(arachidonate:oxygen 12-oxidoreductase)||arachidonate + O2 = (5Z,8Z,10E,12S,14Z)-12-hydroperoxyicosa-5,8,10,14-tetraenoate|
|EC 126.96.36.199||arachidonate 15-lipoxygenase||(arachidonate:oxygen 15-oxidoreductase)||arachidonate + O2 = (5Z,8Z,11Z,13E,15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate|
|EC 188.8.131.52||arachidonate 5-lipoxygenase||(arachidonate:oxygen 5-oxidoreductase)||arachidonate + O2 = leukotriene A4 + H2|
|EC 184.108.40.206||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.
- Powell WS, Rokach J (2015). "Biosynthesis, biological effects, and receptors of hydroxyeicosatetraenoic acids (HETEs) and oxoeicosatetraenoic acids (oxo-ETEs) derived from arachidonic acid". Biochimica et Biophysica Acta. 1851 (4): 340–55. doi:10.1016/j.bbalip.2014.10.008. PMID 25449650.
- Kuhn H, Banthiya S, van Leyen K (2015). "Mammalian lipoxygenases and their biological relevance". Biochimica et Biophysica Acta. 1851 (4): 308–30. doi:10.1016/j.bbalip.2014.10.002. PMC . PMID 25316652.
- Gabbs M, Leng S, Devassy JG, Monirujjaman M, Aukema HM (2015). "Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs". Advances in Nutrition (Bethesda, Md.). 6 (5): 513–40. doi:10.3945/an.114.007732. PMC . PMID 26374175.
- Mashima R, Okuyama T (2015). "The role of lipoxygenases in pathophysiology; new insights and future perspectives". Redox Biology. 6: 297–310. doi:10.1016/j.redox.2015.08.006. PMC . PMID 26298204.
- Capra V, Rovati GE, Mangano P, Buccellati C, Murphy RC, Sala A (2015). "Transcellular biosynthesis of eicosanoid lipid mediators". Biochimica et Biophysica Acta. 1851 (4): 377–82. doi:10.1016/j.bbalip.2014.09.002. PMID 25218301.
- 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.
- KenjiMatsui (2006). "Green leaf volatiles: hydroperoxide lyase pathway of oxylipin metabolism". Current Opinion in Plant Biology. 9: 274–280. doi:10.1016/j.pbi.2006.03.002.
- 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.
- Barden AE, Mas E, Mori TA (2016). "n-3 Fatty acid supplementation and proresolving mediators of inflammation". Current Opinion in Lipidology. 27 (1): 26–32. doi:10.1097/MOL.0000000000000262. PMID 26655290.
- Qu Q, Xuan W, Fan GH (2015). "Roles of resolvins in the resolution of acute inflammation". Cell Biology International. 39 (1): 3–22. doi:10.1002/cbin.10345. PMID 25052386.
- Romano M, Cianci E, Simiele F, Recchiuti A (2015). "Lipoxins and aspirin-triggered lipoxins in resolution of inflammation". European Journal of Pharmacology. 760: 49–63. doi:10.1016/j.ejphar.2015.03.083. PMID 25895638.
- "WikiGenes - Collaborative Publishing". WikiGenes - Collaborative Publishing. Retrieved 17 April 2018.
- "WikiGenes - Collaborative Publishing". WikiGenes - Collaborative Publishing. Retrieved 17 April 2018.
- 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 . PMID 24021977.
- "WikiGenes - Collaborative Publishing". WikiGenes - Collaborative Publishing. Retrieved 17 April 2018.
- 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 . 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 . 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 . 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)
- Blanch Time and Cultivar Effects on Quality of Frozen and Stored Corn and Broccoli - lipoxygenase, peroxidase, cystine lyase enzyme inactivation in blanching
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.
Lipoxygenase Provide feedback
No Pfam abstract.
External database links
This tab holds annotation information from the InterPro database.
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 arachidonate 15-lipoxygenase B (also known as 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)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Number in seed:||101|
|Number in full:||3645|
|Average length of the domain:||426.10 aa|
|Average identity of full alignment:||28 %|
|Average coverage of the sequence by the domain:||70.77 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||19|
|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 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 100 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...