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LMPD Database

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LMP001597

UniProt Annotations

Entry Information

Gene Name	arachidonate 12-lipoxygenase, 12R type
Protein Entry	LX12B_MOUSE
UniProt ID	O70582
Species	Mouse

Comments

Comment type	Description
Catalytic Activity	Arachidonate + O(2) = (5Z,8Z,10E,14Z)-(12R)- 12-hydroperoxyicosa-5,8,10,14-tetraenoate. {ECO:0000269\|PubMed:16129665}.
Cofactor	Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00726}; Note=Binds 1 Fe cation per subunit. {ECO:0000255\|PROSITE- ProRule:PRU00726};
Developmental Stage	In the embryo, expression begins at day 15.5. {ECO:0000269\|PubMed:9837935}.
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. {ECO:0000269\|PubMed:17403930, ECO:0000269\|PubMed:21558561}.
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. {ECO:0000269\|PubMed:16129665, ECO:0000269\|PubMed:17403930, ECO:0000269\|PubMed:17429434, ECO:0000269\|PubMed:21558561}.
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 (PubMed:17429434). {ECO:0000305\|PubMed:17429434}.
Pathway	Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.
Pathway	Lipid metabolism; sphingolipid metabolism.
Similarity	Belongs to the lipoxygenase family. {ECO:0000305}.
Similarity	Contains 1 lipoxygenase domain. {ECO:0000255\|PROSITE- ProRule:PRU00726}.
Similarity	Contains 1 PLAT domain. {ECO:0000255\|PROSITE- ProRule:PRU00152}.
Subcellular Location	Cytoplasm {ECO:0000255\|PROSITE- ProRule:PRU00726}.
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. {ECO:0000269\|PubMed:9518531}.