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FLASH GENE
Symbol ALOX15 contributors: mct/npt - updated : 07-02-2023
HGNC name arachidonate 15-lipoxygenase
HGNC id 433
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
HOMOLOGY
interspecies homolog to murine Alox15
Homologene
FAMILY
  • lipoxygenase family
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • non-heme iron containing dioxygenase, catalyzing the first step of leukotrienes biosynthesis from arachidonate
  • lipid peroxidating enzyme implicated in the pathogenesis of inflammatory disorders as well as membrane remodeling
  • involved in carcinogenesis, and atheroma formation
  • maybe involved in the development of prostate or intestines colorectal carcinomas
  • involved in the translational control and stabilization of mRNAs in erythroid cells
  • cardiac ALOX12/ALOX15 is involved in the development of heart failure
  • ALOX12/ALOX15 mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding
  • ALOX12/ALOX15 is required for the maintenance of long-term hematopoietic stem cells quiescence and number
  • pivotal role of ALOX15 in the resolution of adipocyte death and in adipose tissue remodeling
  • plays an important role in the formation of key lipid mediators (e.g., lipoxins and resolvins) to terminate inflammation
  • most mammalian ALOX15 orthologs exhibit dual positional specificity with highly unsaturated n-3 polyunsaturated fatty acids
  • functions to generate specific phospholipid (PL) oxidation products crucial for orchestrating the nonimmunogenic removal of apoptotic cells (ACs)
  • ALOX15 plays a significant role in promoting the migration of immune cells, such as immature dendritic cells, activated T cells, and mast cells, and airway remodeling, including goblet cell differentiation
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism lipid/lipoprotein
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • iron Fe2+
    • protein
  • binding site for SPI1 (increasing its transcription in the macrophage)
  • vimentin binds the ALOX15 promoter and regulates its promoter activity and protein expression
  • methylated HNRNPK acts on RPS19 to regulate ALOX15 synthesis in erythropoiesis
    • cell & other
    REGULATION
    Other regulated by ERK1/2 (important regulatory role for ERK1/2 in mediating IL13-induced monocyte ALOX15 expression via the transcription factors EGR1 and CREB)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in prostatic adenocarcinoma
    constitutional     --over  
    in heart failure
    tumoral     --other  
    expressed in primary Hodgkin Reed-Sternberg cells in classical Hodgkin lymphoma
    tumoral       loss of function
    in colorectal cancer (CRC)
    Susceptibility
  • to coronary artery disease (CAD)
  • to bone loss, fracture incidence
  • to nasal polyps and chronic rhinosinusitis
    • Variant & Polymorphism SNP , other
  • rs7217186:T>C and rs2619112:G>A of ALOX15 are associated with increased risk of CAD
  • variation in ALOX15 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly
  • a loss-of-function variant in ALOX15 protects against nasal polyps and chronic rhinosinusitis
    • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cardiovascularaquired 
    inhibition of ALOX12/ALOX15 could be a novel treatment for heart failure
    immunologyinfectious 
    ALOX15 pathway is a novel therapeutic target for the treatment of virus-associated asthma characterized by Th1 inflammation
    ANIMAL & CELL MODELS
  • Cardiac fibrosis increased in Alox15 transgenic mice with advancing age and was associated with the infiltration of macrophages
  • Mice lacking Alox15 in &
    • 946; cells exhibit an increase in a population of beta cells expressing the gene encoding the protein programmed death ligand 1 (PD-L1), which engages receptors on immune cells to sssuppress autoimmunity