ALOX5AP (FLAP)

Arachidonate 5-Lipoxygenase-Activating Protein (ALOX5AP), also known as FLAP, belongs to the MAPEG family. ALOX5AP/FLAP is an essential partner of 5-LO for this process. The FLAP (ALOX5AP) gene has been linked to risk for myocardial infarction, stroke and restenosis, reigniting pharmaceutical interest in this target. It had been found that ALOX5AP/FLAP is a key enzyme in leukotriene formation, in both human pulmonary microvascular endothelial cells and a transformed human brain endothelial cell line. In addition, the protein ALOX5AP has recently been identified as an emerging target in metabolic disease. In fact, ALOX5AP is overexpressed in the adipose tissue of patients and experimental animals with obesity and insulin resistance.

ALOX5AP (FLAP) Related Areas

Enzyme>>Lipid Metabolism Enzymes>>ALOX5A/PFLAP

Cardiovascular>>Lipid Metabolism>>Lipid Metabolism Enzymes>>ALOX5A/PFLAP

ALOX5AP (FLAP) Alternative Names

ALOX5AP, FLAP [Homo sapiens]

Alox5ap, Flap [Mus musculus]

Summaries for ALOX5AP (FLAP)

Entrez Gene summary for ALOX5AP:

This ALOX5AP gene encodes a protein which, with 5-lipoxygenase, is required for leukotriene synthesis. Leukotrienes are arachidonic acid metabolites which have been implicated in various types of inflammatory responses, including asthma, arthritis and psoriasis. ALOX5AP localizes to the plasma membrane. Inhibitors of its function impede translocation of 5-lipoxygenase from the cytoplasm to the cell membrane and inhibit 5-lipoxygenase activation. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

Human ALOX5AP (FLAP) Protein General Information

 

• Protein names: Arachidonate 5-lipoxygenase-activating protein
• Sequence length: 161 AA.
• Domain: The C-terminal part after residue 140 is mostly unstructured.
• Sequence similarities: ALOX5AP belongs to the MAPEG family.
• Subunit structure: Homotrimer. Interacts with LTC4S and ALOX5.
• Subcellular location: Nucleus membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein
• Involvement in disease: Genetic variations in ALOX5AP may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; ALOX5AP is also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
  Note=Genetic variations in ALOX5AP may be associated with susceptibility to myocardial infarction. Involvement in myocardial infarction is however unclear: according to some authors, a 4-SNP haplotype in ALOX5AP confers risk of myocardial infarction, while according to other ALOX5AP is not implicated in this condition.

General information above from UniProt

Function for ALOX5AP (FLAP) Protein

UniProtKB:

ALOX5AP is required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). ALOX5AP anchors ALOX5 to the membrane. ALOX5AP binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. ALOX5AP binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.

Genatlas:

• ALOX5AP could play an essential role in the transfer of arachidonic acid to 5-lipoxygenase
• ALOX5AP is involved in the pathogenesis of both myocardial infarction and stroke by increasing leukotriene production and inflammation in the arterial wall

Phenotype Information for ALOX5AP (FLAP)

• Gene/Locus: ALOX5AP, FLAP
• Phenotype: {Stroke, susceptibility to}

Phenotype Information for ALOX5AP from OMIM (Online Mendelian Inheritance in Man)