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FLASH GENE

Symbol

ALOX15

contributors: mct/npt - updated : 07-02-2023

HGNC name	arachidonate 15-lipoxygenase
HGNC id	433

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth         Lymphoid/Immune lymph node         Respiratory respiratory tract trachea       Homo sapiens   respiratory tract bronchiole       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose       Epithelial absorptive excretory alveolar epithelium     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic eosinophil Blood/Hematopoietic leukocyte Blood/Hematopoietic monocyte Homo sapiens Lymphoid/Immune macrophage Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed cardiovascular aquired   inhibition of ALOX12/ALOX15 could be a novel treatment for heart failure immunology infectious   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