ALOX12 - Arachidonate 12-lipoxygenase, 12S-type - human protein (Function)
 
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ALOX12 »  Arachidonate 12-lipoxygenase, 12S-type   [ EC 1.13.11.31 ]  (12S-LOX)
 
Protein also known as:  Platelet-type lipoxygenase 12.
Gene name:  ALOX12
Family name: Lipoxygenase
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Mainly converts arachidonic acid to (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation.  
5
  • CuratedUniProtKB
GO molecular function 
Arachidonate 12-lipoxygenase activitydefinition[GO:0004052]  
4
  • IDAUniProtKB
Hepoxilin-epoxide hydrolase activitydefinition[GO:0047977]  
  • ISSOrtholog Curator
Iron ion bindingdefinition[GO:0005506] silver  
  • IEAInterPro 2 GO
Linoleate 13S-lipoxygenase activitydefinition[GO:0016165]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
GO biological process 
Agingdefinition[GO:0007568] silver  
  • IEAOrtholog Compara
Arachidonic acid metabolic processdefinition[GO:0019369]  
2
  • IDAUniProtKB
  • ISSOrtholog Curator
Cellular component movementdefinition[GO:0006928]  
1
  • IMPUniProtKB
Cellular response to lipiddefinition[GO:0071396] silver  
  • IEAOrtholog Compara
Establishment of skin barrierdefinition[GO:0061436]  
  • ISSOrtholog Curator
Fatty acid oxidationdefinition[GO:0019395]  
1
  • IMPUniProtKB
Hepoxilin biosynthetic processdefinition[GO:0051122]  
  • ISSOrtholog Curator
Contradiction  Leukotriene A4 metabolic processdefinition[GO:1901751]  
2
  • IDAUniProtKB
Contradiction  Linoleic acid metabolic processdefinition[GO:0043651]  
2
  • IDAUniProtKB
Lipoxin A4 biosynthetic processdefinition[GO:2001303]  
1
  • IDAUniProtKB
Lipoxin B4 biosynthetic processdefinition[GO:2001306]  
1
  • IDAUniProtKB
Lipoxygenase pathwaydefinition[GO:0019372]  
1
  • IDAUniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
  • ISSOrtholog Curator
Negative regulation of muscle cell apoptotic processdefinition[GO:0010656]  
1
  • IMPUniProtKB
Negative regulation of platelet aggregationdefinition[GO:0090331]  
  • ISSOrtholog Curator
Positive regulation of angiogenesisdefinition[GO:0045766]  
1
  • IMPUniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065] silver  
  • IEAOrtholog Compara
Positive regulation of cell adhesiondefinition[GO:0045785]  
1
  • IMPUniProtKB
Positive regulation of cell growthdefinition[GO:0030307]  
1
  • IMPUniProtKB
Positive regulation of cell migrationdefinition[GO:0030335]  
1
  • IMPUniProtKB
Positive regulation of cell proliferationdefinition[GO:0008284]  
3
  • IMPUniProtKB
  • ISSOrtholog Curator
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043280] silver  
  • IEAOrtholog Compara
Positive regulation of endothelial cell differentiationdefinition[GO:0045603] silver  
  • IEAOrtholog Compara
Positive regulation of endothelial cell migrationdefinition[GO:0010595] silver  
  • IEAOrtholog Compara
Positive regulation of gene expressiondefinition[GO:0010628] silver  
  • IEAOrtholog Compara
Positive regulation of mitochondrial depolarizationdefinition[GO:0051901] silver  
  • IEAOrtholog Compara
Positive regulation of smooth muscle cell proliferationdefinition[GO:0048661] silver  
  • IEAOrtholog Compara
Positive regulation of vasodilationdefinition[GO:0045909] silver  
  • IEAOrtholog Compara
Reactive oxygen species metabolic processdefinition[GO:0072593]  
1
  • NASUniProtKB
Superoxide anion generationdefinition[GO:0042554]  
1
  • NASUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H(2)O (5S,6R,15S)-trihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate.  
4
  • CuratedUniProtKB
(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H(2)O (5S,14R,15S)-trihydroxy-(6E,8Z,10E,12E)-eicosatetraenoate.  
  • CuratedUniProtKB
EC 1.13.11.31: Arachidonate + O(2) (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.  
4
  • CuratedUniProtKB
It requires the following cofactor
Binds 1 iron ion per subunit.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated by EGF.  
1
  • CuratedUniProtKB
Pathways 
This protein is involved in the following pathway
According to KEGG, this protein belongs to the following pathways:
Arachidonic acid metabolism  hsa00590+239  
Metabolic pathways  hsa01100+239  
According to Reactome, this protein belongs to the following pathway:
Metabolism  REACT_111217  
 
More information is available from:
 

Biophysicochemical properties

Kinetic parameters
KM 6.2 uM for arachidonate (PubMed:8250832, at pH 7.4)
KM 14.3 uM for 5,6-epoxy-8,11,14-eicosatrienoate (PubMed:8250832, at pH 7.4)
KM 3 uM for eicosa-5,8,11,14,17-pentaenoate (PubMed:1851637, at pH 7.0 and 37 degrees Celsius)
KM 35 uM for eicosa-8,11,14-trienoate (PubMed:1851637, at pH 7.0 and 37 degrees Celsius)
KM 7.9 uM for leukotriene A4 (PubMed:8250832, at pH 7.4)
KM 8 uM for arachidonate (PubMed:1851637, at pH 7.0 and 37 degrees Celsius)
KM 10 uM for arachidonate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius)
KM 9 uM for linoleate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius)
Vmax 3 umol/min/mg enzyme with arachidonate as substrate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius)
Vmax 1.057 umol/min/mg enzyme with arachidonate as substrate (PubMed:8250832, at pH 7.4)
Vmax 0.025 umol/min/mg enzyme with leukotriene A4 as substrate (PubMed:8250832, at pH 7.4)
Vmax 0.985 umol/min/mg enzyme with 5,6-epoxy-8,11,14-eicosatrienoate as substrate (PubMed:8250832, at pH 7.4)
Vmax 0.0375 umol/min/mg enzyme with linoleate as substrate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius)
Dependence
pH Optimum pH is 7.5-8.0 (for arachidonate 12-lipoxygenase activity).

Keywords

Biological process 
Fatty acid metabolism  definition   [KW-0276]
Lipid metabolism  definition   [KW-0443]
Molecular function 
Dioxygenase  definition   [KW-0223]
Hydrolase  definition   [KW-0378]
Oxidoreductase  definition   [KW-0560]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: ALOX12
GenomeRNAi: 239
PRO: PR:P18054