ALOX12B Antibody – Mouse Monoclonal

Function: 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 (12R)-hydroperoxyeicosatetraenoic acid/(12R)-HPETE and minor stereoisomers. In the skin, acts upstream of ALOXE3 on the lineolate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss. May also play a role in the regulation of the expression of airway mucins. Ref.3 Ref.4 Ref.5 Ref.6

Catalytic activity: Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. Ref.3

Cofactor: Binds 1 iron ion per subunit

By similarity.

Pathway: Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. Ref.3 Ref.5Lipid metabolism; sphingolipid metabolism. Ref.3 Ref.5

Subcellular location: Cytoplasm

By similarity.

Tissue specificity: Expressed in skin epidermis and other stratified epithelia including tongue and forestomach. Low levels of expression are found in trachea, brain and lung. Not expressed in intestine, liver, kidney, adipose tissue, muscle or hematopoietic cells. Ref.1

Developmental stage: In the embryo, expression begins at day 15.5. Ref.2

Disruption phenotype: Mice die within 3 to 5 hours after birth due to defective skin barrier function loosing around 30% of body weight within 3 hours. Dehydration through the skin is increased 8 folds. The outside-in barrier acquisition is also affected, the skin remaining permeable at E18.5 while it is impermeable in wild-type mice. The stratum corneum is more tightly packed while other layers are unaffected. Processing of filaggrin/FG is aberrant and the skin displays structural abnormalities. The cornified envelope is more fragile and the ceramide composition of the epidermis is altered. Ref.4 Ref.6

Miscellaneous: Mummy, a recessive ethylnitrosurea-induced mutant has a nonsense mutation in the catalytic domain of Lox12b, resulting in truncation of the protein by 68 amino-acids. The affected mice are born with red, shiny skin that dessicates and appears scaly. They probably die of dehydration like mice with targeted disruption of the gene (Ref.5).

Sequence similarities: Belongs to the lipoxygenase family.Contains 1 lipoxygenase domain.Contains 1 PLAT domain.