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Literature summary extracted from
- 5-Lipoxygenase: regulation of expression and enzyme activity (2007), Trends Biochem. Sci., 32, 332-341.
Activating Compound
| EC Number | Activating Compound | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.13.11.34 | 5-LO-activating protein | i.e. FLAP, a small permanently membrane-bound protein that is essential for the biosynthesis of leukotrienes from endogenous arachidonic acid. FLAP binds arachidonic acid and is thought to assist in the provision of substrate to 5-LO | Mus musculus | |
| 1.13.11.34 | 5-LO-activating protein | i.e. FLAP, a small permanently membrane-bound protein that is essential for the biosynthesis of leukotrienes from endogenous arachidonic acid. FLAP binds arachidonic acid and is thought to assist in the provision of substrate to 5-LO | Rattus norvegicus | |
| 1.13.11.34 | ATP | upregulation of 5-LO through the C2-like domain | Mus musculus |  |
| 1.13.11.34 | ATP | upregulation of 5-LO through the C2-like domain | Rattus norvegicus | |
| 1.13.11.34 | ATP | upregulation of 5-LO through the C2-like domain | Homo sapiens | |
| 1.13.11.34 | FLAP | 5-LO-activating protein, a small permanently membrane-bound protein that is essential for the biosynthesis of leukotrienes from endogenous arachidonic acid. FLAP binds arachidonic acid and is thought to assist in the provision of substrate to 5-LO | Homo sapiens | |
| 1.13.11.34 | additional information | coactosin-like protein, i.e. CLP, can bind to 5-LO and supports Ca2+-induced 5-LO enzyme activity. CLP seems to function as a chaperone or scaffold for 5-LO, upregulation of 5-LO through the C2-like domain | Mus musculus | |
| 1.13.11.34 | additional information | coactosin-like protein, i.e. CLP, can bind to 5-LO and supports Ca2+-induced 5-LO enzyme activity. CLP seems to function as a chaperone or scaffold for 5-LO, upregulation of 5-LO through the C2-like domain | Rattus norvegicus | |
| 1.13.11.34 | additional information | coactosin-like protein, i.e. CLP, can bind to 5-LO and supports Ca2+-induced 5-LO enzyme activity. CLP seems to function as a chaperone or scaffold for 5-LO. About 100fold induction of 5-LO mRNA, protein and activity is found after differentiation of HL-60 and human monocytic Mono Mac 6 cells with TGF-beta and 1,25(OH)2D3, upregulation of 5-LO through the C2-like domain. Factors like cell stress and phorbol ester activate MAPK kinases, which phosphorylate the enzyme and enhance its activity and induce nuclear translocation, overview | Homo sapiens |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.13.11.34 | the gene contains 14 exons, DNA methylation is responsible for suppression of 5-LO expression, the 5-LO core promoter is completely methylated in the cell lines U-937 and HL-60TB, which do not express 5-LO protein, regulation mechanisms, overview, expression in HeLa cells, which lack endogenous enzyme, for promoter analysis, the basal promoter undergoes DNA looping to distant gene regions | Homo sapiens |
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 1.13.11.34 | crystal structure analysis | Mus musculus |
| 1.13.11.34 | crystal structure analysis | Rattus norvegicus |
| 1.13.11.34 | crystal structure analysis | Homo sapiens |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.13.11.34 | S271A | site-directed mutagenesis, mutation of the phosphorylation site results in impaired cellular 5-LO product formation when transfected cells are selectively activated by arachidonic acid | Homo sapiens |
| 1.13.11.34 | S663A | site-directed mutagenesis, mutation of the phosphorylation site results in impaired cellular 5-LO product formation when transfected cells are selectively activated by arachidonic acid | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.13.11.34 | glutathione | efficiency of non-redox-type 5-LO inhibitors depends on the presence of glutathione peroxidase activity leading to low hydroperoxide concentration | Homo sapiens | |
| 1.13.11.34 | glutathione | efficiency of non-redox-type 5-LO inhibitors depends on the presence of glutathione peroxidase activity leading to low hydroperoxide concentration | Mus musculus | |
| 1.13.11.34 | glutathione | efficiency of non-redox-type 5-LO inhibitors depends on the presence of glutathione peroxidase activity leading to low hydroperoxide concentration | Rattus norvegicus | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.13.11.34 | cytosol | - |
Mus musculus | 5829 | - |
| 1.13.11.34 | cytosol | - |
Rattus norvegicus | 5829 | - |
| 1.13.11.34 | cytosol | - |
Homo sapiens | 5829 | - |
| 1.13.11.34 | additional information | localization of enzyme and reactions, and activation in the cell, overview | Mus musculus | - |
- |
| 1.13.11.34 | additional information | localization of enzyme and reactions, and activation in the cell, overview | Rattus norvegicus | - |
- |
| 1.13.11.34 | additional information | localization of enzyme and reactions, and activation in the cell, overview | Homo sapiens | - |
- |
| 1.13.11.34 | nucleus | soluble fraction, translocation to the nuclear envelope upon cell activation by Ca2+ | Mus musculus | 5634 | - |
| 1.13.11.34 | nucleus | soluble fraction, translocation to the nuclear envelope upon cell activation by Ca2+ | Rattus norvegicus | 5634 | - |
| 1.13.11.34 | nucleus | soluble fraction, translocation to the nuclear envelope upon cell activation by Ca2+ | Homo sapiens | 5634 | - |
| 1.13.11.34 | soluble | - |
Mus musculus | - |
- |
| 1.13.11.34 | soluble | - |
Rattus norvegicus | - |
- |
| 1.13.11.34 | soluble | - |
Homo sapiens | - |
- |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.13.11.34 | 1-oleoyl-2-acetyl-sn-glycerol | both Ca2+ and glyceride, e.g. 1-oleoyl-2-acetyl-sn-glycerol, might decrease the concentration of lipid hydroperoxide needed for activation of 5-LO, enabling cellular 5-LO product formation at a low redox tone | Mus musculus | |
| 1.13.11.34 | 1-oleoyl-2-acetyl-sn-glycerol | both Ca2+ and glyceride, e.g. 1-oleoyl-2-acetyl-sn-glycerol, might decrease the concentration of lipid hydroperoxide needed for activation of 5-LO, enabling cellular 5-LO product formation at a low redox tone | Rattus norvegicus | |
| 1.13.11.34 | 1-oleoyl-2-acetyl-sn-glycerol | both Ca2+ and glyceride, e.g. 1-oleoyl-2-acetyl-sn-glycerol, might decrease the concentration of lipid hydroperoxide needed for activation of 5-LO, enabling cellular 5-LO product formation at a low redox tone | Homo sapiens | |
| 1.13.11.34 | Ca2+ | binds at the C2-like domain, stimulates and induces enzyme translocation from the nuclear soluble to the envelope fraction, both Ca2+ and glyceride might decrease the concentration of lipid hydroperoxide needed for activation of 5-LO, enabling cellular 5-LO product formation at a low redox tone | Mus musculus | |
| 1.13.11.34 | Ca2+ | binds at the C2-like domain, stimulates and induces enzyme translocation from the nuclear soluble to the envelope fraction, both Ca2+ and glyceride might decrease the concentration of lipid hydroperoxide needed for activation of 5-LO, enabling cellular 5-LO product formation at a low redox tone | Rattus norvegicus | |
| 1.13.11.34 | Ca2+ | binds at the C2-like domain, stimulates and induces enzyme translocation from the nuclear soluble to the envelope fraction, both Ca2+ and glyceride might decrease the concentration of lipid hydroperoxide needed for activation of 5-LO, enabling cellular 5-LO product formation at a low redox tone | Homo sapiens | |
| 1.13.11.34 | Fe3+ | because catalysis by 5-LO requires oxidation of Fe2+ to the active Fe3+ state by lipid hydroperoxides, the redox tone is an important parameter of cellular 5-LO activity | Mus musculus | |
| 1.13.11.34 | Fe3+ | because catalysis by 5-LO requires oxidation of Fe2+ to the active Fe3+ state by lipid hydroperoxides, the redox tone is an important parameter of cellular 5-LO activity | Rattus norvegicus | |
| 1.13.11.34 | Fe3+ | because catalysis by 5-LO requires oxidation of Fe2+ to the active Fe3+ state by lipid hydroperoxides, the redox tone is an important parameter of cellular 5-LO activity | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | Mus musculus | - |
leukotriene A4 + H2O | a conjugated epoxide intermediate in leukotriene biosynthesis, is unstable and enzymatically metabolized to leukotriene B4 or by spontaneous hydrolysis | ? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | Rattus norvegicus | - |
leukotriene A4 + H2O | a conjugated epoxide intermediate in leukotriene biosynthesis, is unstable and enzymatically metabolized to leukotriene B4 or by spontaneous hydrolysis | ? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | Homo sapiens | - |
leukotriene A4 + H2O | a conjugated epoxide intermediate in leukotriene biosynthesis, is unstable and enzymatically metabolized to leukotriene B4 or by spontaneous hydrolysis | ? | |
| 1.13.11.34 | arachidonic acid + O2 | Mus musculus | - |
(6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| 1.13.11.34 | arachidonic acid + O2 | Rattus norvegicus | - |
(6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| 1.13.11.34 | arachidonic acid + O2 | Homo sapiens | - |
(6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| 1.13.11.34 | additional information | Mus musculus | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | ? | - |
? | |
| 1.13.11.34 | additional information | Rattus norvegicus | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | ? | - |
? | |
| 1.13.11.34 | additional information | Homo sapiens | key enzyme in the leukotriene biosynthesis, pathway overview, the 5-LO pathway is linked to the development of cardiovascular disease and other diseases, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | ? | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.13.11.34 | Homo sapiens | P09917 | - |
- |
| 1.13.11.34 | Mus musculus | - |
- |
- |
| 1.13.11.34 | Rattus norvegicus | - |
- |
- |
Posttranslational Modification
| EC Number | Posttranslational Modification | Comment | Organism |
|---|---|---|---|
| 1.13.11.34 | phosphoprotein | the amino acid sequence of 5-LO contains several protein kinase motifs, e.g. at Ser271 and Ser663, 5-LO is phosphorylated in vitro by the protein kinases p38 MAPK-regulated MAPKAPK-2/3, ERK1/2, CaMKII and PKA. Conditions that activate MAPKAPKs and ERKs (e.g. cell stress, and phorbol esters) induce nuclear translocation of 5-LO and enhance product formation in intact cells, and this process is susceptible to kinase inhibitors. Phosphorylation on Ser523 by PKA directly suppresses 5-LO catalysis both in vitro and in the cell, and prevents nuclear localization of 5-LO by inhibiting the nuclear import function of a nuclear import sequence close to the kinase motif | Homo sapiens |
Source Tissue
| EC Number | Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|---|
| 1.13.11.34 | brain | - |
Rattus norvegicus | - |
| 1.13.11.34 | carcinoma cell | - |
Homo sapiens | - |
| 1.13.11.34 | HL-60 cell | - |
Homo sapiens | - |
| 1.13.11.34 | leukocyte | - |
Mus musculus | - |
| 1.13.11.34 | leukocyte | - |
Rattus norvegicus | - |
| 1.13.11.34 | leukocyte | - |
Homo sapiens | - |
| 1.13.11.34 | Mono-Mac-6 cell | a monocytic cell line | Homo sapiens | - |
| 1.13.11.34 | additional information | expression of 5-LO is much higher in differentiated myeloid cells and cell lines than in undifferentiated cells, cell lines HeLa, U-937 and HL-60TB do not express 5-LO protein | Homo sapiens | - |
| 1.13.11.34 | prostate cancer cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Mus musculus | leukotriene A4 + H2O | - |
? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Rattus norvegicus | leukotriene A4 + H2O | - |
? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Homo sapiens | leukotriene A4 + H2O | - |
? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Mus musculus | leukotriene A4 + H2O | a conjugated epoxide intermediate in leukotriene biosynthesis, is unstable and enzymatically metabolized to leukotriene B4 or by spontaneous hydrolysis | ? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Rattus norvegicus | leukotriene A4 + H2O | a conjugated epoxide intermediate in leukotriene biosynthesis, is unstable and enzymatically metabolized to leukotriene B4 or by spontaneous hydrolysis | ? | |
| 1.13.11.34 | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Homo sapiens | leukotriene A4 + H2O | a conjugated epoxide intermediate in leukotriene biosynthesis, is unstable and enzymatically metabolized to leukotriene B4 or by spontaneous hydrolysis | ? | |
| 1.13.11.34 | arachidonic acid + O2 | - |
Mus musculus | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| 1.13.11.34 | arachidonic acid + O2 | - |
Rattus norvegicus | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| 1.13.11.34 | arachidonic acid + O2 | - |
Homo sapiens | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| 1.13.11.34 | additional information | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | Mus musculus | ? | - |
? | |
| 1.13.11.34 | additional information | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | Rattus norvegicus | ? | - |
? | |
| 1.13.11.34 | additional information | key enzyme in the leukotriene biosynthesis, pathway overview, the 5-LO pathway is linked to the development of cardiovascular disease and other diseases, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | Homo sapiens | ? | - |
? | |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.13.11.34 | 5-lipoxygenase | - |
Mus musculus |
| 1.13.11.34 | 5-lipoxygenase | - |
Rattus norvegicus |
| 1.13.11.34 | 5-lipoxygenase | - |
Homo sapiens |
| 1.13.11.34 | 5-LO | - |
Mus musculus |
| 1.13.11.34 | 5-LO | - |
Rattus norvegicus |
| 1.13.11.34 | 5-LO | - |
Homo sapiens |
| 1.13.11.34 | LTA4 synthase | - |
Mus musculus |
| 1.13.11.34 | LTA4 synthase | - |
Rattus norvegicus |
| 1.13.11.34 | LTA4 synthase | - |
Homo sapiens |
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