lmmol · Proteins

Polyunsaturated fatty acid 5-lipoxygenase

UniProt P09917 Organism Homo sapiens Gene ALOX5, LOG5 EC 1.13.11.-, 1.13.11.34

Also known as: ALOX5, LOG5

Function

Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation. Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene. Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses. Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers. In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40. May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).

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
Nucleotide & Amino-Acid Biosynthesis Enzymes

Experimental structures · PDB · 9

A predicted model is available from AlphaFold.

Gene Ontology · 47

Drugs targeting this protein · 8

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 35 cited papers

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