5-lipoxygenase-activating protein

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Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5AP gene.[1][2]


FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes, 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and specialized pro-resolving mediators of the lipoxin and resolvin classes.[3][4] It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. FLAP structure consist of 4 transmembrane alpha helices, but they are found in 3’s( trimer) forming a barrel. The barrel is about 60 A high and 36 A wide.[5]

Clinical significance

Gene polymorphisms in FLAP are suspected of playing a role in Alzheimer's disease.[6] Leukotrienes, which need the FLAP protein to be made, have an established pathological role in allergic and respiratory diseases. Animal and human genetic evidence suggests they may also have an important role in atherosclerosis, myocardial infarction, and stroke. The structure of FLAP provides a tool for the development of novel therapies for respiratory and cardiovascular diseases and for the design of focused experiments to probe the cell biology of FLAP and its role in leukotriene biosynthesis.[5]



  1. Kennedy BP, Diehl RE, Boie Y, Adam M, Dixon RA (May 1991). "Gene characterization and promoter analysis of the human 5-lipoxygenase-activating protein (FLAP)". The Journal of Biological Chemistry. 266 (13): 8511–6. PMID 1673682.
  2. Yandava CN, Kennedy BP, Pillari A, Duncan AM, Drazen JM (February 1999). "Cytogenetic and radiation hybrid mapping of human arachidonate 5-lipoxygenase-activating protein (ALOX5AP) to chromosome 13q12". Genomics. 56 (1): 131–3. doi:10.1006/geno.1998.5651. PMID 10036194.
  3. Peters-Golden M, Brock TG (2003). "5-lipoxygenase and FLAP". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 69 (2–3): 99–109. doi:10.1016/S0952-3278(03)00070-X. PMID 12895592.
  4. Serhan CN, Chiang N, Dalli J, Levy BD (2015). "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology. 7 (2): a016311. doi:10.1101/cshperspect.a016311. PMC 4315926. PMID 25359497.
  5. 5.0 5.1 PDB: 2q7r​;Ferguson AD, McKeever BM, Xu S, Wisniewski D, Miller DK, Yamin TT, Spencer RH, Chu L, Ujjainwalla F, Cunningham BR, Evans JF, Becker JW (July 2007). "Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein". Science. 317 (5837): 510–2. doi:10.1126/science.1144346. PMID 17600184.
  6. Manev H, Manev R (2006). "5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and Alzheimer's disease". Medical Hypotheses. 66 (3): 501–3. doi:10.1016/j.mehy.2005.09.031. PMID 16278051.
  7. Musiyenko A, Correa L, Stock N, Hutchinson JH, Lorrain DS, Bain G, Evans JF, Barik S (November 2009). "A novel 5-lipoxygenase-activating protein inhibitor, AM679, reduces inflammation in the respiratory syncytial virus-infected mouse eye". Clinical and Vaccine Immunology. 16 (11): 1654–9. doi:10.1128/CVI.00220-09. PMC 2772391. PMID 19759251.

Further reading

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