lmmol · Proteins

Polyunsaturated fatty acid lipoxygenase ALOX12

UniProt P18054 Organism Homo sapiens Gene 12LO, ALOX12, LOG12 EC 1.13.11.-, 1.13.11.31, 1.13.11.33

Also known as: 12LO, ALOX12, LOG12

Function

Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species. Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE. Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It can also catalyze the epoxidation of double bonds of polyunsaturated fatty acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the formation of (13S,14S)-epoxy-DHA. Furthermore, it may participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets. An additional function involves a multistep process by which it transforms leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil function via occupancy of specific recognition sites. Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE) (By similarity). Due to its role in regulating both the expression of the vascular endothelial growth factor (VEGF, an angiogenic factor involved in the survival and metastasis of solid tumors) and the expression of integrin beta-1 (known to affect tumor cell migration and proliferation), it can be regarded as protumorigenic. Important for cell survival, as it may play a role not only in proliferation but also in the prevention of apoptosis in vascular smooth muscle cells.

Classification

Family (Pfam)
PF00305 Lipoxygenase, PF01477 PLAT
InterPro
LipOase, LipOase_C, LipOase_C_sf, LipOase_CS, LipOase_Fe_BS, LipOase_mml, PLAT/LH2_dom, PLAT/LH2_dom_sf, PLAT_LOX_verte
Functional cluster
Membrane Channels & Lipid-Anchored Proteins

Experimental structures · PDB · 5

A predicted model is available from AlphaFold.

Gene Ontology · 25

Disease associations

Drugs targeting this protein · 1

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 28 cited papers

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