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Information on EC 1.13.11.31 - arachidonate 12-lipoxygenase and Organism(s) Mus musculus and UniProt Accession O70582
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1.13.11.31 arachidonate 12-lipoxygenaseIUBMB Comments
The product is rapidly reduced to the corresponding 12S-hydroxy compound.
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Word Map
- 1.13.11.31
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arachidonic
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cyclooxygenase
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12-hete
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eicosanoids
- prostaglandin
- endothelial
- phospholipase
- neutrophil
- atherosclerosis
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polyunsaturated
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linoleic
- artery
- baicalein
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lipoxins
-
hetes
- monocyte
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12-hydroxyeicosatetraenoic
- cox-2
- reticulocyte
- asthma
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nordihydroguaiaretic
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thromboxane
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eicosapentaenoic
- hydroperoxide
- ndga
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polymorphonuclear
- atherogenesis
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docosahexaenoic
- indomethacin
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5,8,11,14-eicosatetraynoic
- etya
- zileuton
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13-hode
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hydroperoxy
- lipoxygenase-1
- erythroderma
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hydroxyeicosatetraenoic
- medicine
- esculetin
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protectins
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ichthyosiform
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resolvins
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polyenoic
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pro-resolving
- drug development
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14carachidonic
- ichthyosis
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ferroptosis
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5-lipoxygenase-activating
- phenidone
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a23187-stimulated
- oxylipins
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
12-lipoxygenase, 15-lipoxygenase, 12-lox, alox5, 15-lox-1, alox15, 12-lo, 15-lo, 12/15-lipoxygenase, 12/15-lox, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
12-lipoxygenase
12-LOX
12/15 lipoxygenase
12/15-lipoxygenase
12/15-LO
12/15-LOX
12/15LO
12DELTA-lipoxygenase
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12S-lipoxygenase
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Alox15
C-12 lipoxygenase
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DELTA 12-lipoxygenase
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leukotriene A4 synthase M
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LTA4 synthase
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oygenase, arachidonate 12-lip-
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Platelet-type lipoxygenase 12
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12-lipoxygenase
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12-LOX
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12/15-lipoxygenase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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oxidation
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reduction
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dioxygenation
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dehydration
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PATHWAY SOURCE
PATHWAYS
BRENDA
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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
82391-43-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
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
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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
-
?
5,8,11,14,17-eicosapentaenoic acid + O2
12-hydroxy-5,8,10,14,17-eicosapentaenoic acid
-
-
12-hydroxyeicosapentaenoic acid
?
5,8,11-eicosatrienoic acid + O2
12-hydroxy-5,8,10-eicosatrienoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
-
?
6,9,12-octadecatrienoic acid + O2
13-hydroxy-6,9,12-octadecatrienoic acid
-
-
-
?
arachidonic acid methyl ester + O2
12-hydroxyeicosatetraenoic acid methyl ester
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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
?
linoleic acid methyl ester + O2
13(S)-hydroperoxyoctadecadienoic acid methyl ester
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activity with epidermal-type (12S)-lipoxygenase, no activity with platelet-type (12S)-lipoxygenase and (12R)-lipoxygenase
-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
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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-
?
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
mouse Alox12b protein, 12R-LOX, oxygenates arachidonate methyl ester rather than arachidonic acid to 12(R)-hydroperoxyeicosatetraenoic acid, HETE
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?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,12,16,19-docosahexaenoic acid
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?
4,7,10,13,16,19-docosahexaenoic acid + O2
14-hydroxy-4,7,10,12,16,19-docosahexaenoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
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?
8,11,14-eicosatrienoic acid + O2
12-hydroxyeicosatrienoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
12-hydroxy-8,10,14-eicosatrienoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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12-H(p)ETE is the major reaction product of 12/15-LOX independent of the pH
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?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
platelet-type (12S)-lipoxygenase produces (12S)-hydroxyeicosatetraenoic acid and (8R)-hydroxyeicosatetraenoic acid, epidermal-type (12S)-lipoxygenase produces only 12-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
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?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
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?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
leukocyte-type enzyme produces 12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid, platelet-type enzyme produces only 12-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
platelet-type (12S)-lipoxygenase produces (12S)-hydroxyeicosatetraenoic acid and (8R)-hydroxyeicosatetraenoic acid, epidermal-type (12S)-lipoxygenase produces only 12-hydroxyeicosatetraenoic acid
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
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i.e. 5Z,8Z,11Z,14Z-eicosatetraenoic acid
12-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic acid in the ratio of 6:1
?
linoleic acid + O2
13(S)-hydroperoxy-9Z,11E-octadecadienoic acid
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activity with platelet-type (12S)-lipoxygenase and epidermal-type (12S)-lipoxygenase, no activity with (12R)-lipoxygenase
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?
additional information
?
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Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
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?
additional information
?
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Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
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?
additional information
?
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the 12-lipoxygenase pathway plays a critical role in angiogenesis
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?
additional information
?
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12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses
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?
additional information
?
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increased expression of 12-LO has deleterius effects in beta cells
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?
additional information
?
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lipoxin A4 and docosahexaenoic acid-derived neuroprotectin D1 are lipid autacoids formed by 12/15-lipoxygenase pathway that exhibit anti-inflammatory and neuroprotective properties. The enzyme also shows action in wound healing that is distinct from the anti-inflammatory properties
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?
additional information
?
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a bifunctional enzyme exhibiting 12-LO and 15-LO activity, the enzyme is also able to catalyze stereoselective oxidation of linoleic acid at position 13 over 9 to preferentially form 13(S)-hydroperoxyoctadienoic acid, which enhances MCP-1 expression, overview
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?
additional information
?
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reactive oxygen species formation catalyzed by 12-LOX
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?
additional information
?
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12/15-LOX generates (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate and (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate, when arachidonic acid is the substrate, the enzyme produces small amounts of 15S-HETE and primarily 12S-HETE (ratio of 1:3). In case of linolenic acid as a substrate, 13S-hydroxyoctadecadienoic acid (13S-HODE) is generated via the interstage product 13S-hydroperoxyoctadecadienoic acid (13SHPODE). Inflammatory eicosanoids are produced by eosinophils in a 12/15-LOX dependent manner. Another family of 12/15-LOX products are hepoxilins. They are enzymatic products of the conversion of 12S-HPETE, but can also be produced by non-enzymatic modification of 12S-HPETE or 12RHPETE. In the latter case, hemine or haemoglobin may act as a non-specific catalyst
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?
additional information
?
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the enzymatic peroxidation reaction consists of four consecutive steps: At first a hydrogen atom is stereoselectively abstracted from one of the bisallylic methylene-groups forming an enzyme-bound radical. Secondly one of the two associated cis-double bonds is rearranged and forms a conjugated cis-trans-diene. Consecutively a peroxy radical is produced by inserting molecular oxygen. Finally the radical is reduced by antarafacial re-inserting of a hydrogen atom. The resulting product of this peroxidation reaction depends on the respective fatty acid, which is used as a substrate
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
arachidonate methyl ester + O2
(5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate methyl ester
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
-
-
?
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
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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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?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
-
?
arachidonate + O2
(5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate
-
-
-
?
additional information
?
-
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
?
additional information
?
-
-
Alox12b deficiency in mice leads to a lack of epidermal permeability barrier function and perinatal lethality
-
-
?
additional information
?
-
-
the 12-lipoxygenase pathway plays a critical role in angiogenesis
-
-
?
additional information
?
-
-
12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses
-
-
?
additional information
?
-
-
increased expression of 12-LO has deleterius effects in beta cells
-
-
?
additional information
?
-
-
lipoxin A4 and docosahexaenoic acid-derived neuroprotectin D1 are lipid autacoids formed by 12/15-lipoxygenase pathway that exhibit anti-inflammatory and neuroprotective properties. The enzyme also shows action in wound healing that is distinct from the anti-inflammatory properties
-
-
?
additional information
?
-
12/15-LOX generates (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate and (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate, when arachidonic acid is the substrate, the enzyme produces small amounts of 15S-HETE and primarily 12S-HETE (ratio of 1:3). In case of linolenic acid as a substrate, 13S-hydroxyoctadecadienoic acid (13S-HODE) is generated via the interstage product 13S-hydroperoxyoctadecadienoic acid (13SHPODE). Inflammatory eicosanoids are produced by eosinophils in a 12/15-LOX dependent manner. Another family of 12/15-LOX products are hepoxilins. They are enzymatic products of the conversion of 12S-HPETE, but can also be produced by non-enzymatic modification of 12S-HPETE or 12RHPETE. In the latter case, hemine or haemoglobin may act as a non-specific catalyst
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?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
ML355
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a selective 12-LOX inhibitor, blocks both FcgammaRIIa-induced platelet aggregation and (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate production
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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baicalein
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p12-LOX specific inhibitor, suppresses proliferation of JB6 P+ cells when cells are seeded at a low density in a culture plate by 81%
baicalein
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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 AA861
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
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
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platelet-type enzyme is the 12-lipoxygenase isoform responsible for the generation of most of the 12-hydroxyeicosateteaenoic acid
additional information
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12/15-LOX is selectively enhanced in the periphery, 12/15-LOX-expressing myeloid cells are enriched in the brain during chronic toxoplasmosis
eosinophils are the major cell type expressing 12/15-LOX during the corneal wound healing process
expression of 12/15-LOX pathway is upregulated in the diabetic heart
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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
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12/15-LOX is a macrophage-selective regulator of interleukin-12 production
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12/15-LOX is expressed by 95% of resident peritoneal CD11bhigh cells, with the remaining 5% being 12/15-LOX-. 12/15-LOX+ cells are phenotypically defined by high F4/80, SR-A, and Siglec1 expression, and enhanced IL-10 and G-CSF generation. In contrast, 12/15-LOX- cells are a dendritic cell population. Resident peritoneal macrophage numbers are significantly increased in 12/15-LOX-/- mice, suggesting alterations in migratory trafficking or cell differentiation in vivo
macrophages that overexpress 12/15LO have reduced ATP-binding cassette G1 expression, increased transporter phosphorylation, and reduced cholesterol efflux
additional information
-
expression of p12-LOX is significantly higher in JB6P+ cells than in JB6P- cells that are resistant to transformation
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
gene ALOX15 encodes for human 15-LOX type 1 and murine 12/15-LOX. Although the encoded enzymes display slightly different specificities (15- versus 12-lipoxygenating activity), these proteins represent evolutionary and functionally closely-related enzymes that share a high degree of sequence similarity. Of note, these 12/15LOXs that are encoded by the ALOX15 genes have separated from other LOXs early during evolution, although they share close biochemical properties with other LOXs such as ALOX12 or ALOX15B
malfunction
metabolism
cardiac 12/15-LOX pathway induced by high glucose condition increases the expression of cardiac inflammation in vitro
physiological function
malfunction
macrophages that lack 12/15LO have enhanced transporter expression, reduced ATP-binding cassette G1 phosphorylation, and increased cholesterol efflux
malfunction
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the time to cessation of bleeding in 12-LOX-/- mice is significantly prolonged. Mice deficient in 12-LOX show a significant attenuation of alphaIIbeta3 activation for both agonists compared to wild-type mice
malfunction
-
deletion of 12/15-LOX in mice leads to increased cytochrome P450-derived bioactive lipid mediator epoxyeicosatrienoic acids, i.e. 11,12-EpETrE and 14,15-EpETrE, which are further enhanced by acute PUFA intake post-MI. Macrophage density is decreased in wild-type + PUFA and 12/15-LOX-/- mice compared with their respective standard diet-fed wild-type controls at day 5 post-MI. 12/15-LOX-/- + PUFA mice display an increased expression of chemokine (C-C motif) ligand 2 and reparative macrophages markers (Ym-1, Mrc-1, and Arg-1) in the infarcted area. Furthermore, 12/15-LOX-/- mice, with or without PUFA, show reduced collagen deposition at day 5 post-MI compared with wild-type mice. In conclusion, deletion of 12/15-LOX and short-term exposure of PUFA promote leukocyte clearance, thereby limiting cardiac remodeling and promoting an effective resolution of inflammation
malfunction
-
platelets from transgenic mice expressing human FcgammaRIIa but deficient in platelet 12-LOX, fail to form normal platelet aggregates and exhibit deficiencies in Rap1 and aIIbbeta3 activation
malfunction
streptozotocin (STZ)-induced diabetic mice show upregulated expression of 12/15-LOX and inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and nuclear factor (NF)-kappaB in diabetic hearts. Disruption of 12/15-LOX significantly improves STZ-induced cardiac dysfunction and fibrosis. Deletion of 12/15-LOX inhibits the increases of TNF-alpha and NF-kappaB as well as the production of STZ-induced reactive oxygen species in the heart. Administration of N-acetylcysteine in diabetic mice prevents STZ-induced cardiac fibrosis. Neonatal cultured cardiomyocytes exposed to high glucose conditions induce the expression of 12/15-LOX as well as TNF-alpha, NF-kappaB, and collagen markers. These increases are inhibited by treatment of the 12/15-LOX inhibitor. Disruption of 12/15-LOX reduces inflammation, oxidative stress, and fibrosis in the diabetic heart, thereby improving systolic dysfunction. Disruption of 12/15-LOX decreases cardiac inflammation induced by hyperglycemia
malfunction
the cytokine expression profile of Alox15-/- dendritic cells show multiple alterations in comparison to that for wild-type dendritic cells. Alox15/ dendritic cells display a shift in the mRNA and protein expression of different IL-12/IL-23 subunits and increased expression of the IL-23-specific subunit p19, whereas expression of the subunit p40 (shared by IL-12 and IL-23) is unaltered and the IL-12-specific subunit p35 is decreased. Alox15-deficient mice display an increased differentiation of Th17 cells and an aggravation of T celldependent autoimmune responses, Alox15-/- mice reveal significant increase in the expression of the IL-23 subunit p19, whereas expression levels of the IL-12/IL-23 subunits p35 and p40 are not significantly changed
physiological function
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12/15-LOX is a critical mediator of the chronic type 1 inflammatory response. Evolution of the immune response to Toxoplasma gondii is accompanied by an increasing requirement for 12/15-LOX mediated signaling. Although 12/15-LOX deficient mice are resistant to acute Toxoplasma gondii infection, 80% of 12/15-LOX-deficient mice die during chronic toxoplasmosis, compared to no deaths in wild-type controls. The enhanced susceptibility of 12/15-LOX-deficient mice to chronic toxoplasmosis is associated with reduced production of IL-12 and gamma interferon (IFN-gamma) that is not evident during acute infection. Ex vivo IFN-gamma production by 12/15-LOX-deficient splenocytes can be rescued by the addition of recombinant IL-12. 12/15-LOX does not play a role in macrophage killing of Toxoplasma gondii in vitro
physiological function
-
12/15-LOX is the central executioner in an oxidative stress-related neuronal death program. In neuronal HT22 cells subjected to glutamate-induced oxidative stress, 12/15-LOX damages mitochondria, which represents the committed step that condemns the cell to die. Mitochondria incubated with 12/15-LOX generate reactive oxygen species
physiological function
-
12/15LO expression increases chemokine production. 2/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding. Adipose tissue from high fat diet-fed 12/15LO KO mice is not infiltrated by macrophages and does not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. 12/15LO KO mice exhibit no high fat diet-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output. Insulin-stimulated Akt phosphorylation in muscle tissue from high fat diet-fed mice is significantly greater in 12/15LO KO mice than in wild-type mice
physiological function
12/15LO plays a key role in activating the mitogen-activated protein kinase pathway. 12/15LO regulates ATP-binding cassette G1 expression and function through p38- and c-Jun N-terminal kinase 2-dependent mechanisms
physiological function
-
anti-inflammatory and tissue-protective role of 12/15-LO and its eicosanoidic products during chronic inflammatory disorders such as arthritis. 12/15-LO-deficient mice show enhanced inflammatory gene expression and decreased levels of the eicosanoid lipoxin A(4) within their inflamed synovia. 12/15-LO-deficient macrophages display significantly reduced levels of lipoxin A(4), which correlate with increased activation of p38MAPK and an enhanced inflammatory gene expression after stimulation with TNF-alpha
physiological function
-
endogenous 12/15-LOX defines the resident peritoneal macrophage population and regulates both the recruitment of monocytes/peritoneal macrophage and cytokine response to bacterial products in vivo
physiological function
-
increased expression of 2/15-LOX causes heart failure. 2/15-LOX induces cardiac inflammation. Alox15 transgenic mice develop systolic dysfunction. Cardiac fibrosis increases in Alox15 transgenic mice with advancing age and is associated with the infiltration of macrophages. Cardiac expression of monocyte chemoattractant protein 1 is up-regulated in Alox15 transgenic mice compared with wild-type mice. Disruption of 12/15-LOX significantly reduces cardiac monocyte chemoattractant protein-1 expression and macrophage infiltration, thereby improving systolic dysfunction induced by chronic pressure overload
physiological function
-
p12-LOX plays an important role in tumor development, is required for tumor promotion of epidermal cells. The enzyme is involved in activation of NF-kappaB in the tumor necrosis factor-alpha-stimulated JB6 P+ cells
physiological function
-
the 12/15-LO pathway participates in the regulation of monocyte chemoattractant protein-1 expression in mouse macrophages
physiological function
12/15-lipoxygenase derived metabolites, hydroxyeicosatetraenoic acids (HETEs), contribute to diabetic retinopathy via NADPH oxidase (NOX) and disruption of the balance in retinal levels of the vascular endothelial growth factor and pigment epithelium-derived factor. Pigment epithelium-derived factor inhibits retinal microvascular dysfunction induced by 12/15-lipoxygenase-derived eicosanoids, i.e. (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate, mechanism, overview. 12-HETE stimulates inflammatory cytokine production such as interleukin IL-6 and TNF-alpha from retinal Müller cells (rMCs)
physiological function
12/15-lipoxygenase-meditated (12/15-LO-mediated) enzymatic lipid oxidation regulates dendritic cell activation and fine-tunes consecutive T cell responses. 12/15-LO activity determines the dendritic cell activation threshold via generation of phospholipid oxidation products that induce an antioxidative response dependent on the transcription factor NRF2. Dendritic cells comprise a heterogenic group of antigen-presenting cells, which share the ability to prime naive T cells. 12/15-LO regulates the maturation process of human dendritic cell (DC). DC-intrinsic 12/15-LO activity attenuates Th17 T cell differentiation. NRF2 mediates the immune-modulatory effects of 12/15-LO-derived oxidized phospholipids
physiological function
12/15-LOX is implicated in the pathogenesis of multiple chronic inflammatory diseases, and its physiologic functions seem to include potent immune modulatory properties that physiologically contribute to the resolution of inflammation and the clearance of inflammation-associated tissue damage. 12/15-LOXs are also involved in the synthesis of lipoxins, which likewise act as anti-inflammatory, pro-resolving mediators. Inflammatory eicosanoids are produced by eosinophils in a 12/15-LOX dependent manner. Docosahexaenoic acid (DHA) is a further substrate of 12/15-LOX. The oxidation of DHA leads to the production of 17S-hydroxy-DHA, an anti-inflammatory mediator, which can be further metabolized into highly active and potent anti-inflammatory resolvins and protectins. 12/15-LOX can metabolize not only free PUFAs, but also PUFAs esterified to membrane-bound phospholipids as well as PUFAs within cholesterol esters. 12/15-LOX-derived mediators as regulators of inflammation, role of 12/15-LOX during inflammation, detailed overview. 12/15-LOX activity in resident macrophages interferes with theMFG-E8-dependent uptake of apoptotic cells (ACs) by inflammatory, immune-competent phagocytes and thereby fosters the non-immunogenic clearance of ACs, whereas 12/15-LOX-derived lipoxins directly increase the non-inflammatory uptake of dying cells. Possible role of 12/15-LOX in atherosclerosis
physiological function
cardiac 12/15-LOX-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy. 12/15-LOX induces cardiac oxidative stress in the diabetic heart
physiological function
-
murine platelets require 12-LOX for normal FcgammaRIIa-induced platelet aggregation
physiological function
-
the metabolic transformation of fatty acids to form oxylipids using 12/15-lipoxygenase (LOX) can promote either resolving or nonresolving inflammation. 12/15-LOX interacts with polyunsaturated fatty acids (PUFA) in postmyocardial infarction (post-MI) healing, mechanism, overview
physiological function
12/15-LOX-deficient mice display augmented IL-33-induced lung inflammation, characterized by an increased number of infiltrated eosinophils and group 2 innate lymphoid cells in the airway. The levels of a series of 12/15-LOX-derived metabolites are significantly decreased, and application of 14(S)-hydroxy docosahexaenoic acid suppresses IL-33-mediated eosinophilic inflammation in 12/15-LOX-deficient mice. 14(S)-hydroxy docosahexaenoic acid and 10(S),17(S)-dihydroxy docosahexaenoic acid markedly attenuate ILC2 proliferation and cytokine production at micromolar concentration in vitro
physiological function
a sharp increase in protein expression of 12/15 lipoxygenase is found in the pancreatic islets of 10-week old db-/- obese diabetic mice compared to 8-week old counterparts. The increase in islet 12/15 lipoxygenase parallels a decline in islet number. A 2- to 3fold increase especially in 12(S)-hydroperoxytetraeicosanoid acid mirrors the increase in 12/15 lipoxygenase expression in islets. A significant increase of platelet 12/15 lipoxygenase gene expression is found along with 12-hydroperoxytetraeicosanoid acids and 15-hydroperoxytetraeicosanoid acids
physiological function
activity of 12S-lipoxygenase is hardly observed in liver cytosol of normal chow-fed mice but is clearly detectable in that of nonalcoholic steatohepatitis model mice prepared. The expression levels of mRNA and protein of platelet-type 12S-lipoxygenase in the liver of methionine- and choline-deficient diet-fed mice are significantly increased compared with those of normal chow-fed mice. Platelet-type 12S-lipoxygenase colocalizes with alpha-smooth muscle actin as well as vitamin A in the cells distributing along liver sinusoids
physiological function
cold and beta3-adrenergic stimulation can promote the biosynthesis and release of 12-LOX metabolites from brown adipose tissue. 12-LOX ablation in brown adipocytes impaires glucose uptake and metabolism, resulting in blunted adaptation to the cold in vivo. The cold-induced 12-LOX product 12-hydroxyeicosapentaenoic acid is a batokine that improves glucose metabolism by promoting glucose uptake into adipocytes and skeletal muscle through activation of an insulin-like intracellular signaling pathway
physiological function
eosinophils are the major cell type expressing 12/15-LOX during the corneal wound healing process. Eosinophils are recruited into the conjunctiva after corneal epithelium wounding, and eosinophil-deficient and/or eosinophil-specific 12/15-LOX knockout mice show delayed corneal wound healing compared with wild-type mice. A series of 12/15-LOX-derived mediators are significantly decreased in eosinophil-deficient mice and topical application of 17-hydroxydocosahexaenoic acid restores the phenotype
physiological function
male Balb/c mice subjected to simulated hypobaric hypoxia for three consecutive days show a robust increase in intra-hippocampal (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate level, which is significantly reduced following baicalein treatment. The elevated level of (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyeicosa-5,8,10,14-tetraenoate correlates with simultaneous increase in expression of 12/15 LOX in neurons and microglia lining the hippocampal CA3 region. 12/15 LOX gets embedded onto the periphery of mitochondria following hypobaric hypoxia and a strong correlation is observed with loss of mitochondrial integrity
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
lipoxygenases are composed of a N-terminal beta-barrel domain and a larger C-terminal catalytic domain harboring a non-heme iron in its active side
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
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
-
mutant shows strongly impared catalytic activity, relative catalytic activity: 3.2% compared to wild-type 100%
T570M
-
mutant shows strongly impared catalytic activity, relative catalytic activity: 8.2% compared to wild-type 100%
additional information
additional information
-
12/15-LO knockout mice show reduced monocyte chemoattractant protein MCP-1 expression
additional information
generation of Alox15-deficient (12/15-LOX KO) mice
additional information
generation of enzyme-deficient Alox15-/- mice, phenotype, overview
additional information
-
generation of enzyme-deficient Alox15-/- mice, phenotype, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
genotyping, overexpression of His-tagged mutant W633X and wild-type Alox12b proteins in COS7 cells
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)
-
rat beta INS-1 cells are transduced with adeno-associated virus vector ACSM12-LO, that encodes mouse leukocyte type 12-lipoxygenase
-
two cDNA clones encoding the platelet-type and the leukocyte-type isoforms expressed in COS-7 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
12/15-LOX is markedly upregulated in heart failure, cardiac expression is upregulated during pressure overload
-
12/15-LOX mRNA expression in cultured aortic smooth muscle cells is upregulated by angiotensin II, ATII. ATII also stimulates production of LOX-derived HETEs in arterial vessels and the kidney
a sharp increase in protein expression of 12/15 lipoxygenase is found in the pancreatic islets of 10-week old db-/- obese diabetic mice compared to 8-week old counterparts
reduced monocyte chemoattractant protein-1 expression in mouse peritoneal macrophages from 12/15-LO null mice
-
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
-
tumor necrosis factor-alpha induces p12-LOX in the early stage of tumorigenesis, induces p12-LOX expression both in JB6P+ and JB6P- cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
drug development
-
cardiac 12/15-LOX is involved in the development of heart failure and inhibition of 12/15-LOX may be a novel treatment for this condition
drug development
-
inhibition of 12/15-LOX provides robust protection against cell death preventing mitochondrial damage in oxidative stress-related brain injury
drug development
-
p12-LOX pathway may be an effective target of chemoprevention for skin carcinogenesis
medicine
-
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
medicine
activity of 12S-lipoxygenase is hardly observed in liver cytosol of normal chow-fed mice but is clearly detectable in that of nonalcoholic steatohepatitis model mice prepared by feeding a methionine and choline-deficient diet
medicine
application of 14(S)-hydroxy docosahexaenoic acid suppresses IL-33-mediated eosinophilic inflammation in 12/15-LOX-deficient mice. 14(S)-hydroxy docosahexaenoic acid and 10(S),17(S)-dihydroxy docosahexaenoic acid markedly attenuate ILC2 proliferation and cytokine production at micromolar concentration in vitro. Maresin 1 (MaR1) and resolvin D1 (RvD1), 12/15-LOX-derived specialized proresolving mediators (SPMs), inhibited cytokine production of ILC2s at nanomolar concentration
medicine
Streptococcus pneumoniae infection of the respiratory epithelium induces the production of the 12-lipoxygenase-dependent lipid inflammatory mediator hepoxilin A3, which promotes recruitment of neutrophils into the airways, tissue damage, and lethal septicemia. A pneumolysin-deficient S. pneumoniae mutant is impaired in triggering human neutrophil transepithelial migration in vitro
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JOURNAL
VOL.
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YEAR
ORGANISM (UNIPROT)
PUBMED ID
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Koshihara, Y.; Mizumura, M.; Murota, S.I.
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Mus musculus
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Characterization of the murine epidermal 12/15-lipoxygenase
Prostaglandins Other Lipid Mediat.
63
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2001
Mus musculus
Krieg, P.; Kinzig, A.; Ress-Lschke, M.; Vogel, S.; Vanlandingham, B.; Stephan, M.; Lehmann, W.D.; Marks, F.; Furstenberger, G.
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14
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Homo sapiens, Mus musculus
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Homo sapiens, Mus musculus, Rattus norvegicus
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Enzymic characterization of epidermis-derived 12-lipoxygenase isoenzymes
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355
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2001
Mus musculus
Prasad, K.M.; Thimmalapura, P.R.; Woode, E.A.; Nadler, J.L.
Evidence that increased 12-lipoxygenase expression impairs pancreatic beta cell function and viability
Biochem. Biophys. Res. Commun.
308
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2003
Mus musculus
Gronert, K.; Maheshwari, N.; Khan, N.; Hassan, I.R.; Dunn, M.; Laniado Schwartzman, M.
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Mus musculus
Feinmark, S.J.; Begum, R.; Tsvetkov, E.; Goussakov, I.; Funk, C.D.; Siegelbaum, S.A.; Bolshakov, V.Y.
12-lipoxygenase metabolites of arachidonic acid mediate metabotropic glutamate receptor-dependent long-term depression at hippocampal CA3-CA1 synapses
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2003
Mus musculus
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67
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2005
Mus musculus
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Arterioscler. Thromb. Vasc. Biol.
26
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2006
Mus musculus
Wen, Y.; Gu, J.; Vandenhoff, G.E.; Liu, X.; Nadler, J.L.
Role of 12/15-lipoxygenase in the expression of MCP-1 in mouse macrophages
Am. J. Physiol. Heart Circ. Physiol.
294
H1933-H1938
2008
Mus musculus, Sus scrofa
Assimes, T.L.; Knowles, J.W.; Priest, J.R.; Basu, A.; Borchert, A.; Volcik, K.A.; Grove, M.L.; Tabor, H.K.; Southwick, A.; Tabibiazar, R.; Sidney, S.; Boerwinkle, E.; Go, A.S.; Iribarren, C.; Hlatky, M.A.; Fortmann, S.P.; Myers, R.M.; Kuhn, H.; Risch, N.; Quertermous, T.
A near null variant of 12/15-LOX encoded by a novel SNP in ALOX15 and the risk of coronary artery disease
Atherosclerosis
198
136-144
2008
Homo sapiens, Mus musculus, Mus musculus C57BL/6
Moran, J.L.; Qiu, H.; Turbe-Doan, A.; Yun, Y.; Boeglin, W.E.; Brash, A.R.; Beier, D.R.
A mouse mutation in the 12R-lipoxygenase, Alox12b, disrupts formation of the epidermal permeability barrier
J. Invest. Dermatol.
127
1893-1897
2007
Mus musculus (O70582), Mus musculus, Mus musculus A/J (O70582)
Walther, M.; Roffeis, J.; Jansen, C.; Anton, M.; Ivanov, I.; Kuhn, H.
Structural basis for pH-dependent alterations of reaction specificity of vertebrate lipoxygenase isoforms
Biochim. Biophys. Acta
1791
827-835
2009
Danio rerio, Mus musculus
Piao, Y.S.; Du, Y.C.; Oshima, H.; Jin, J.C.; Nomura, M.; Yoshimoto, T.; Oshima, M.
Platelet-type 12-lipoxygenase accelerates tumor promotion of mouse epidermal cells through enhancement of cloning efficiency
Carcinogenesis
29
440-447
2008
Mus musculus
Chou, D.S.; Hsiao, G.; Lai, Y.A.; Tsai, Y.J.; Sheu, J.R.
Baicalein induces proliferation inhibition in B16F10 melanoma cells by generating reactive oxygen species via 12-lipoxygenase
Free Radic. Biol. Med.
46
1197-1203
2009
Mus musculus
Middleton, M.K.; Zukas, A.M.; Rubinstein, T.; Kinder, M.; Wilson, E.H.; Zhu, P.; Blair, I.A.; Hunter, C.A.; Pure, E.
12/15-lipoxygenase-dependent myeloid production of interleukin-12 is essential for resistance to chronic toxoplasmosis
Infect. Immun.
77
5690-5700
2009
Mus musculus, Mus musculus C57BL/6
Nagelin, M.H.; Srinivasan, S.; Nadler, J.L.; Hedrick, C.C.
Murine 12/15-lipoxygenase regulates ATP-binding cassette transporter G1 protein degradation through p38- and JNK2-dependent pathways
J. Biol. Chem.
284
31303-31314
2009
Mus musculus (P39654), Mus musculus
Kayama, Y.; Minamino, T.; Toko, H.; Sakamoto, M.; Shimizu, I.; Takahashi, H.; Okada, S.; Tateno, K.; Moriya, J.; Yokoyama, M.; Nojima, A.; Yoshimura, M.; Egashira, K.; Aburatani, H.; Komuro, I.
Cardiac 12/15 lipoxygenase-induced inflammation is involved in heart failure
J. Exp. Med.
206
1565-1574
2009
Mus musculus
Dioszeghy, V.; Rosas, M.; Maskrey, B.H.; Colmont, C.; Topley, N.; Chaitidis, P.; Kuehn, H.; Jones, S.A.; Taylor, P.R.; ODonnell, V.B.
12/15-Lipoxygenase regulates the inflammatory response to bacterial products in vivo
J. Immunol.
181
6514-6524
2008
Mus musculus, Mus musculus C57BL/6
Kroenke, G.; Katzenbeisser, J.; Uderhardt, S.; Zaiss, M.M.; Scholtysek, C.; Schabbauer, G.; Zarbock, A.; Koenders, M.I.; Axmann, R.; Zwerina, J.; Baenckler, H.W.; van den Berg, W.; Voll, R.E.; Kuehn, H.; Joosten, L.A.; Schett, G.
12/15-lipoxygenase counteracts inflammation and tissue damage in arthritis
J. Immunol.
183
3383-3389
2009
Mus musculus
Pallast, S.; Arai, K.; Wang, X.; Lo, E.H.; van Leyen, K.
12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress
J. Neurochem.
111
882-889
2009
Mus musculus
Sears, D.D.; Miles, P.D.; Chapman, J.; Ofrecio, J.M.; Almazan, F.; Thapar, D.; Miller, Y.I.
12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice
PLoS ONE
4
e7250
2009
Mus musculus, Mus musculus C57BL6
Schurmann, K.; Anton, M.; Ivanov, I.; Richter, C.; Kuhn, H.; Walther, M.
Molecular basis for the reduced catalytic activity of the naturally occurring T560M mutant of human 12/15-lipoxygenase that has been implicated in coronary artery disease
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286
23920-23927
2011
Homo sapiens, Mus musculus
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12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity
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110
569-581
2013
Homo sapiens, Mus musculus
Halade, G.V.; Kain, V.; Ingle, K.A.; Prabhu, S.D.
Interaction of 12/15-lipoxygenase with fatty acids alters the leukocyte kinetics leading to improved postmyocardial infarction healing
Am. J. Physiol. Heart Circ. Physiol.
313
H89-H102
2017
Mus musculus, Mus musculus C57BL/6J
Ibrahim, A.S.; Tawfik, A.M.; Hussein, K.A.; Elshafey, S.; Markand, S.; Rizk, N.; Duh, E.J.; Smith, S.B.; Al-Shabrawey, M.
Pigment epithelium-derived factor inhibits retinal microvascular dysfunction induced by 12/15-lipoxygenase-derived eicosanoids
Biochim. Biophys. Acta
1851
290-298
2015
Mus musculus (P39654), Mus musculus C57BL/6J (P39654)
Ackermann, J.A.; Hofheinz, K.; Zaiss, M.M.; Kroenke, G.
The double-edged role of 12/15-lipoxygenase during inflammation and immunity
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1862
371-381
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Mus musculus (P39654)
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Platelet 12-LOX is essential for FcgammaRIIa-mediated platelet activation
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2271-2279
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Mus musculus, Homo sapiens (O75342), Homo sapiens
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Arachidonate 12/15-lipoxygenase-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy
Diabetes
64
618-630
2015
Mus musculus (P39654), Mus musculus C57BL/6 (P39654)
Rothe, T.; Gruber, F.; Uderhardt, S.; Ipseiz, N.; Roessner, S.; Oskolkova, O.; Blueml, S.; Leitinger, N.; Bicker, W.; Bochkov, V.N.; Yamamoto, M.; Steinkasserer, A.; Schett, G.; Zinser, E.; Kroenke, G.
12/15-Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function
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125
1944-1954
2015
Homo sapiens (P16050), Homo sapiens, Mus musculus (P39654), Mus musculus, Mus musculus C57BL/6 (P39654)
Leiria, L.O.; Wang, C.H.; Lynes, M.D.; Yang, K.; Shamsi, F.; Sato, M.; Sugimoto, S.; Chen, E.Y.; Bussberg, V.; Narain, N.R.; Sansbury, B.E.; Darcy, J.; Huang, T.L.; Kodani, S.D.; Sakaguchi, M.; Rocha, A.L.; Schulz, T.J.; Bartelt, A.; Hotamisligil, G.S.; Hirshman, M.F.; van Leyen, K.; Goodyear, L.J.; Blueher, M.
12-Lipoxygenase regulates cold adaptation and glucose metabolism by producing the omega-3 lipid 12-HEPE from brown fat
Cell Metab.
30
768-783.e7
2019
Homo sapiens, Mus musculus (P55249), Mus musculus
Ogawa, M.; Ishihara, T.; Isobe, Y.; Kato, T.; Kuba, K.; Imai, Y.; Uchino, Y.; Tsubota, K.; Arita, M.
Eosinophils promote corneal wound healing via the 12/15-lipoxygenase pathway
FASEB J.
34
12492-12501
2020
Mus musculus (P39654)
Miyata, J.; Yokokura, Y.; Moro, K.; Arai, H.; Fukunaga, K.; Arita, M.
12/15-Lipoxygenase regulates IL-33-induced eosinophilic airway inflammation in mice
Front. Immunol.
12
687192
2021
Mus musculus (P39654)
Mori, Y.; Kawakami, Y.; Kanzaki, K.; Otsuki, A.; Kimura, Y.; Kanji, H.; Tanaka, R.; Tsukayama, I.; Hojo, N.; Suzuki-Yamamoto, T.; Kawakami, T.; Takahashi, Y.
Arachidonate 12S-lipoxygenase of platelet-type in hepatic stellate cells of methionine and choline-deficient diet-fed mice
J. Biochem.
168
455-463
2020
Mus musculus (P39655)
Adams, W.; Bhowmick, R.; Bou Ghanem, E.N.; Wade, K.; Shchepetov, M.; Weiser, J.N.; McCormick, B.A.; Tweten, R.K.; Leong, J.M.
Pneumolysin induces 12-lipoxygenase-dependent neutrophil migration during Streptococcus pneumoniae infection
J. Immunol.
204
101-111
2020
Homo sapiens, Mus musculus (P55249)
Dobrian, A.D.; Huyck, R.W.; Glenn, L.; Gottipati, V.; Haynes, B.A.; Hansson, G.I.; Marley, A.; McPheat, W.L.; Nadler, J.L.
Activation of the 12/15 lipoxygenase pathway accompanies metabolic decline in db/db pre-diabetic mice
Prostaglandins Other Lipid Mediat.
136
23-32
2018
Mus musculus (P39654), Mus musculus
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