Information on EC 1.13.11.31 - arachidonate 12-lipoxygenase and Organism(s) Mus musculus and UniProt Accession O70582

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Mus musculus
UNIPROT: O70582


The taxonomic range for the selected organisms is: Mus musculus

The enzyme appears in selected viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.13.11.31
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RECOMMENDED NAME
GeneOntology No.
arachidonate 12-lipoxygenase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dehydration
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dioxygenation
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oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
arachidonic acid metabolism
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Arachidonic acid metabolism
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SYSTEMATIC NAME
IUBMB Comments
arachidonate:oxygen 12-oxidoreductase
The product is rapidly reduced to the corresponding 12S-hydroxy compound.
CAS REGISTRY NUMBER
COMMENTARY hide
82391-43-3
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain A/J
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
show the reaction diagram
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
show the reaction diagram
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(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate increases expression of monocyte chemoattractant protein MCP-1 in macrophages, also but less by 15(S)-hydroxyeicosatetranoic acid, and 12(S)-HETE activates NADPH oxidase, overview, i.e. 12(S)-HPETE and 12(S)-HETE, the first is the predominant product
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?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,12,16,19-docosahexaenoic acid
show the reaction diagram
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
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?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,13,16,19-docosahexaenoic acid
show the reaction diagram
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?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
show the reaction diagram
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12-hydroxyeicosapentaenoic acid
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5,8,11-eicosatrienoic acid + O2
12-hydroxy-5,8,10-eicosatrienoic acid
show the reaction diagram
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
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?
6,9,12-octadecatrienoic acid + O2
13-hydroxy-6,9,12-octadecatrienoic acid
show the reaction diagram
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?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
show the reaction diagram
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
show the reaction diagram
arachidonic acid + O2
?
show the reaction diagram
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?
arachidonic acid methyl ester + O2
12-hydroxyeicosatetraenoic acid methyl ester
show the reaction diagram
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activity with (12R)-lipoxygenase and epidermal-type-(12S)-lipoxygenase, no activity with platelet-type (12S)-lipoxygenase
epidermal-type (12S)-lipoxygenase produces only 12-hydroxyeicosatetraenoic acid methyl ester, (12R)-lipoxygenase produces (12R)-hydroxyeicosatetraenoic acid methyl ester and (4R)-hydroxyeicosatetraenoic acid methyl ester
?
gamma-linolenic acid + O2
10-hydroxy-octadeca-6Z,8E,12Z-trienoic acid
show the reaction diagram
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?
linoleic acid + O2
13(S)-hydroxy-9Z,11E-octadecadienoic acid
show the reaction diagram
linoleic acid methyl ester + O2
13(S)-hydro(pero)xyoctadecadienoic acid methyl ester
show the reaction diagram
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activity with epidermal-type (12S)-lipoxygenase, no activity with platelet-type (12S)-lipoxygenase and (12R)-lipoxygenase
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?
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
show the reaction diagram
O70582
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE, and to 12(R)-HETE methyl ester
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?
2 arachidonate + 2 O2 + 2 H+
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate + (5Z,8Z,10E,14Z)-(12S)-12-hydroxyeicosa-5,8,10,14-tetraenoate + H2O
show the reaction diagram
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(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate increases expression of monocyte chemoattractant protein MCP-1 in macrophages, also but less by 15(S)-hydroxyeicosatetranoic acid, and 12(S)-HETE activates NADPH oxidase, overview
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?
additional information
?
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
AA861
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prevents cell death, the 12/15-LOX inhibitor and the proteasome protect against exogenous glutamate, but not by preventing glutathione depletion. LOX inhibition, but not proteasome inhibition, reduces oxidative stress in glutamate-treated HT22 cells. The mitochondrial membrane potential is protected by coinhibition with baicalien
baicalein
cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate
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N-benzyl-N-hydroxy-5-phenylpentanamide
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PD146176
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selective inhibitor of 12/15-LOX, macrophages treated with PD146176 elaborate reduced levels of interleukin-12 in response to Toxoplasma gondii antigen
siRNA
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inhibition of p12-LOX in JB6 P+ cells by siRNA transfection, causes a significant suppression of 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic transformation by 61% compared with that in control cells
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additional information
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physico-chemical state of the substrate and the complex equilibrium between fatty acid monomers, acid soaps and micelles may impact the reaction specificity of LOX-isoforms
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
7.3 - 7.9
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
assay at
25
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assay at
25 - 37
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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most tumors show constitutive overexpression of platelet-type mRNA, leukocyte-type specific transcripts are detectable only in a few tumors
Manually annotated by BRENDA team
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capillary endothelial cell line CD4
Manually annotated by BRENDA team
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macrophage cell line
Manually annotated by BRENDA team
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platelet-type enzyme is the 12-lipoxygenase isoform responsible for the generation of most of the 12-hydroxyeicosateteaenoic acid
Manually annotated by BRENDA team
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expression of both platelet and leukocyte-type 12-lipoxygenase in distal convoluted tubule cell line. mDCT cells show an active 12-LOX metabolism that appears to be modulated by cAMP and vasopressin
Manually annotated by BRENDA team
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very high 12-lipoxygenase activity
Manually annotated by BRENDA team
additional information
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expression of p12-LOX is significantly higher in JB6P+ cells than in JB6P- cells that are resistant to transformation
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
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half-life: less than 1 h
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, 10% glycerol
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4°C, half-life: less than 1 h
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
on Ni column
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using Ni-NTA chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
genotyping, overexpression of His-tagged mutant W633X and wild-type Alox12b proteins in COS7 cells
expressed in Escherichia coli as a His-tagged fusion protein
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expression in HEK 293 cells
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expression in HEK-293 cells by using the eukaryotic expression vector pcDNA3
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full-length cDNA for 12/15LO subcloned into vector pACCMVpLpA. Bone marrow-derived macrophages infected at a multiplicity of infection of 50 for 48 h with recombinant adenoviral vector AdLO to overexpress 12/15LO
ligated into the pQE-9 plasmid and expressed as N-terminal His-tag fusion protein in Escherichia coli (XL-1 Blue)
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rat beta INS-1 cells are transduced with adeno-associated virus vector ACSM12-LO, that encodes mouse leukocyte type 12-lipoxygenase
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transgenic mice overexpressing 12/15-LOX in cardiomyocytes
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two cDNA clones encoding the platelet-type and the leukocyte-type isoforms expressed in COS-7 cells
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
12/15-LOX activity is enhanced during chronic, but not acute, toxoplasmosis
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12/15-LOX is markedly upregulated in heart failure, cardiac expression is upregulated during pressure overload
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reduced monocyte chemoattractant protein-1 expression in mouse peritoneal macrophages from 12/15-LO null mice
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siRNA decreases 12-LOX protein expression and hydroxyl radical signals occur in a 12-LOX small interfering RNA knockdown protein group compared with the baicalein control
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strong expression of 12/15-LO in inflammatory synovial tissue
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tumor necrosis factor-alpha induces p12-LOX in the early stage of tumorigenesis, induces p12-LOX expression both in JB6P+ and JB6P- cells
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
W633X
naturally occurring mummy mutation, that introduces a nonsense codon into the C-terminal LOX catalytic domain, which results in truncation of the protein by 68 amino acids, mummy is identified in an ethylnitrosurea mutagenesis screen for autosomal recessive developmental phenotypes, the mutant is catalytically inactive, Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
Q303L
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mutant shows strongly impared catalytic activity, relative catalytic activity: 3.2% compared to wild-type 100%
T570M
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mutant shows strongly impared catalytic activity, relative catalytic activity: 8.2% compared to wild-type 100%
additional information
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12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
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prevention of increased 12-LO expression or activity in pancreatic beta cells could be a new way to prevent inflammation and damage to beta cells