InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ALOXE3

Summary

InnateDB Protein

IDBP-367269.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ALOXE3

Protein Name

arachidonate lipoxygenase 3

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000400581

InnateDB Gene

IDBG-27882 (ALOXE3)

Protein Structure

UniProt Annotation

Function

Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols. The dioxygenase activity requires a step of activation of the enzyme by molecular oxygen. In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides. In the skin, acts downstream of ALOX12B on the linoleate 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. In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites. Plays also a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG. Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia. {ECO:0000269PubMed:12881489, ECO:0000269PubMed:17045234, ECO:0000269PubMed:20921226, ECO:0000269PubMed:20923767, ECO:0000269PubMed:21558561}.

Subcellular Localization

Cytoplasm {ECO:0000255PROSITE- ProRule:PRU00726}.

Disease Associations

Ichthyosis, congenital, autosomal recessive 3 (ARCI3) [MIM:606545]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269PubMed:11773004, ECO:0000269PubMed:16116617, ECO:0000269PubMed:19131948, ECO:0000269PubMed:19890349}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Predominantly expressed in skin.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 5 experimentally validated interaction(s) in this database.

Experimentally validated
Total	5 [view]
Protein-Protein	3 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005506	iron ion binding
GO:0005515	protein binding
GO:0016702	oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
GO:0046872	metal ion binding
GO:0051120	hepoxilin A3 synthase activity

Biological Process

GO:0006665	sphingolipid metabolic process
GO:0019233	sensory perception of pain
GO:0019369	arachidonic acid metabolic process
GO:0019372	lipoxygenase pathway
GO:0035357	peroxisome proliferator activated receptor signaling pathway
GO:0043651	linoleic acid metabolic process
GO:0045444	fat cell differentiation
GO:0046513	ceramide biosynthetic process
GO:0051122	hepoxilin biosynthetic process
GO:0055114	oxidation-reduction process
GO:0061436	establishment of skin barrier