Any feedback?
Literature summary for 1.13.11.34 extracted from
- 5-Lipoxygenase: regulation of expression and enzyme activity (2007), Trends Biochem. Sci., 32, 332-341.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| 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 | |
| 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 | |
| ATP | upregulation of 5-LO through the C2-like domain | Mus musculus |  |
| ATP | upregulation of 5-LO through the C2-like domain | Rattus norvegicus | |
| ATP | upregulation of 5-LO through the C2-like domain | Homo sapiens | |
| 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 | |
| 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 | |
| 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 | |
| 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)
| Cloned (Comment) | Organism |
|---|---|
| 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)
| Crystallization (Comment) | Organism |
|---|---|
| crystal structure analysis | Mus musculus |
| crystal structure analysis | Rattus norvegicus |
| crystal structure analysis | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| 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 |
| 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
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| glutathione | efficiency of non-redox-type 5-LO inhibitors depends on the presence of glutathione peroxidase activity leading to low hydroperoxide concentration | Homo sapiens | |
| glutathione | efficiency of non-redox-type 5-LO inhibitors depends on the presence of glutathione peroxidase activity leading to low hydroperoxide concentration | Mus musculus | |
| 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
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Mus musculus | 5829 | - |
| cytosol | - |
Rattus norvegicus | 5829 | - |
| cytosol | - |
Homo sapiens | 5829 | - |
| additional information | localization of enzyme and reactions, and activation in the cell, overview | Mus musculus | - |
- |
| additional information | localization of enzyme and reactions, and activation in the cell, overview | Rattus norvegicus | - |
- |
| additional information | localization of enzyme and reactions, and activation in the cell, overview | Homo sapiens | - |
- |
| nucleus | soluble fraction, translocation to the nuclear envelope upon cell activation by Ca2+ | Mus musculus | 5634 | - |
| nucleus | soluble fraction, translocation to the nuclear envelope upon cell activation by Ca2+ | Rattus norvegicus | 5634 | - |
| nucleus | soluble fraction, translocation to the nuclear envelope upon cell activation by Ca2+ | Homo sapiens | 5634 | - |
| soluble | - |
Mus musculus | - |
- |
| soluble | - |
Rattus norvegicus | - |
- |
| soluble | - |
Homo sapiens | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| 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-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-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 | |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| (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 | ? | |
| (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 | ? | |
| (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 | ? | |
| arachidonic acid + O2 | Mus musculus | - |
(6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| arachidonic acid + O2 | Rattus norvegicus | - |
(6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| arachidonic acid + O2 | Homo sapiens | - |
(6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| additional information | Mus musculus | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | ? | - |
? | |
| additional information | Rattus norvegicus | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | ? | - |
? | |
| 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
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P09917 | - |
- |
| Mus musculus | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| 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
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Rattus norvegicus | - |
| carcinoma cell | - |
Homo sapiens | - |
| HL-60 cell | - |
Homo sapiens | - |
| leukocyte | - |
Mus musculus | - |
| leukocyte | - |
Rattus norvegicus | - |
| leukocyte | - |
Homo sapiens | - |
| Mono-Mac-6 cell | a monocytic cell line | Homo sapiens | - |
| 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 | - |
| prostate cancer cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Mus musculus | leukotriene A4 + H2O | - |
? | |
| (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Rattus norvegicus | leukotriene A4 + H2O | - |
? | |
| (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
Homo sapiens | leukotriene A4 + H2O | - |
? | |
| (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 | ? | |
| (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 | ? | |
| (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 | ? | |
| arachidonic acid + O2 | - |
Mus musculus | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| arachidonic acid + O2 | - |
Rattus norvegicus | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| arachidonic acid + O2 | - |
Homo sapiens | (6E,8Z,11Z,14Z)-(5S)-5-hydroperoxyeicosa-6,8,11,14-tetraenoate | - |
? | |
| additional information | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | Mus musculus | ? | - |
? | |
| additional information | key enzyme in the leukotriene biosynthesis, pathway overview, regulatory mechanisms underlying the expression and control of 5-LO activity, overview | Rattus norvegicus | ? | - |
? | |
| 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
| Synonyms | Comment | Organism |
|---|---|---|
| 5-lipoxygenase | - |
Mus musculus |
| 5-lipoxygenase | - |
Rattus norvegicus |
| 5-lipoxygenase | - |
Homo sapiens |
| 5-LO | - |
Mus musculus |
| 5-LO | - |
Rattus norvegicus |
| 5-LO | - |
Homo sapiens |
| LTA4 synthase | - |
Mus musculus |
| LTA4 synthase | - |
Rattus norvegicus |
| LTA4 synthase | - |
Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
