Gene Symbol: Alox5ap
Description: arachidonate 5-lipoxygenase activating protein
Alias: arachidonate 5-lipoxygenase-activating protein, 5-lipoxygenase-activating protein FLAP, FLAP, MK-886-binding protein
Species: rat
Products:     Alox5ap

Top Publications

  1. Dixon R, Diehl R, Opas E, Rands E, Vickers P, Evans J, et al. Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature. 1990;343:282-4 pubmed
    ..Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP).
  2. Miller D, Gillard J, Vickers P, Sadowski S, Leveille C, Mancini J, et al. Identification and isolation of a membrane protein necessary for leukotriene production. Nature. 1990;343:278-81 pubmed
    ..We have now used these potent agents to identify and isolate a novel membrane protein of relative molecular mass 18,000 which is necessary for cellular leukotriene synthesis. ..
  3. Woods J, Evans J, Ethier D, Scott S, Vickers P, Hearn L, et al. 5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes. J Exp Med. 1993;178:1935-46 pubmed
    The intracellular distribution of the enzyme 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in resting and ionophore-activated human leukocytes has been determined using immuno-electronmicroscopic labeling of ultrathin ..
  4. Pergola C, Gerstmeier J, Mönch B, Caliskan B, Luderer S, Weinigel C, et al. The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP). Br J Pharmacol. 2014;171:3051-64 pubmed publisher
    ..derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis...
  5. Yoshida T, Kato K, Yokoi K, Watanabe S, Metoki N, Yoshida H, et al. Association of genetic variants with chronic kidney disease in Japanese individuals with type 2 diabetes mellitus. Int J Mol Med. 2009;23:529-37 pubmed
    ..for covariates as well as a stepwise forward selection procedure revealed that the 8733T-->C polymorphism of ALOX5AP (rs3803278), the C-->T (Ser532Leu) polymorphism of IRAK1 (rs1059703), and the 2445G-->A (Ala54Thr) ..
  6. Helgadottir A, Manolescu A, Thorleifsson G, Gretarsdottir S, Jonsdottir H, Thorsteinsdottir U, et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet. 2004;36:233-9 pubmed
    ..A four-marker single-nucleotide polymorphism (SNP) haplotype in this locus spanning the gene ALOX5AP encoding 5-lipoxygenase activating protein (FLAP) is associated with a two times greater risk of myocardial ..
  7. Montero A, Uda S, Kelavkar U, Yoshimura A, Badr K, Munger K. Increased 5-lipoxygenase activating protein in immune-mediated experimental nephritis. J Nephrol. 2003;16:682-90 pubmed
    The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid...
  8. Sayers I, Barton S, Rorke S, Sawyer J, Peng Q, Beghe B, et al. Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. Clin Exp Allergy. 2003;33:1103-10 pubmed
    ..We sought to identify novel promoter polymorphisms within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in ..
  9. Goulet J, Byrum R, Key M, Nguyen M, Wagoner V, Koller B. Genetic factors determine the contribution of leukotrienes to acute inflammatory responses. J Immunol. 2000;164:4899-907 pubmed
    ..Taken together, these findings indicate that the relative contribution of prostanoids and LT to inflammatory responses is variable not only between strains but also between different tissues within these inbred mouse lines. ..

More Information


  1. Koshino T, Takano S, Houjo T, Sano Y, Kudo K, Kihara H, et al. Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the peripheral blood leukocytes of asthmatics. Biochem Biophys Res Commun. 1998;247:510-3 pubmed
    ..Therefore, we examined the expression of 5-LO and FLAP mRNAs in the peripheral blood leukocytes (PBL) of 10 asthmatics and 10 controls...
  2. Wright L, Tuder R, Wang J, Cool C, Lepley R, Voelkel N. 5-Lipoxygenase and 5-lipoxygenase activating protein (FLAP) immunoreactivity in lungs from patients with primary pulmonary hypertension. Am J Respir Crit Care Med. 1998;157:219-29 pubmed
    ..5-LO), with translocation of the enzyme to the nuclear membrane, and association with the 5-LO activating protein (FLAP)...
  3. Wang J, John E, Ingles S. 5-lipoxygenase and 5-lipoxygenase-activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:2748-54 pubmed publisher
    ..area to examine the association of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk...
  4. Torres Galván S, Cumplido J, Buset N, Caballero Hidalgo A, Blanco C, Hernandez E, et al. 5-Lipoxygenase pathway gene polymorphisms: lack of association with asthma in a Spanish population. J Investig Allergol Clin Immunol. 2009;19:453-8 pubmed
    ..The promoter polymorphisms LTC4S -444 A/C, ALOX5 -176/-147, and ALOX5AP -169/-146 have been reported to be associated with bronchial asthma...
  5. Patel N, Gonsalves C, Yang M, Malik P, Kalra V. Placenta growth factor induces 5-lipoxygenase-activating protein to increase leukotriene formation in sickle cell disease. Blood. 2009;113:1129-38 pubmed publisher
    ..We show that expression of 5-lipoxygenase and 5-lipoxygenase activating protein (FLAP), key catalytic molecules in the LT pathway, were significantly increased in peripheral blood mononuclear cells (..
  6. Lee H, Lee Y, Kang C, Bae S, Jeoung D, Jang J, et al. Differential gene signatures in rat mammary tumors induced by DMBA and those induced by fractionated gamma radiation. Radiat Res. 2008;170:579-90 pubmed publisher
    ..calcium activated 3 (Clca3) were expressed in both, and that arachidonate 5-lipoxygenase activating protein 1 (Alox5ap) and cathepsin S (Ctss) were expressed only in radiation-induced tumors...
  7. Strid T, Svartz J, Franck N, Hallin E, Ingelsson B, Soderstrom M, et al. Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein. Biochem Biophys Res Commun. 2009;381:518-22 pubmed publisher
    ..5-Lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP) and leukotriene C(4) synthase (LTC(4)S) participate in its biosynthesis...
  8. Brock T, Paine R, Peters Golden M. Localization of 5-lipoxygenase to the nucleus of unstimulated rat basophilic leukemia cells. J Biol Chem. 1994;269:22059-66 pubmed
    ..microscopy has identified the nuclear membrane as the site at which 5-LO, as well as 5-LO activating protein (FLAP), are localized in activated cells, the locale of soluble 5-LO in unstimulated cells could not be established by ..
  9. Bäck M, Sultan A, Ovchinnikova O, Hansson G. 5-Lipoxygenase-activating protein: a potential link between innate and adaptive immunity in atherosclerosis and adipose tissue inflammation. Circ Res. 2007;100:946-9 pubmed
    ..Gene array analyses identified the 5-lipoxygenase-activating protein (FLAP) among the most upregulated genes in both the aorta and adipose tissue of dnTGFbetaRII transgenic ApoE(-/-) mice ..
  10. Liu J, Sun K, Bai Y, Zhang W, Wang X, Wang Y, et al. Association of three-gene interaction among MTHFR, ALOX5AP and NOTCH3 with thrombotic stroke: a multicenter case-control study. Hum Genet. 2009;125:649-56 pubmed publisher
    ..A significant gene-gene interaction was found by GMDR. The best model including MTHFR C677T, ALOX5AP T2354A and NOTCH3 C381T scored 10 for Cross-Validation Consistency and 9 for Sign Test (P = 0.0107)...
  11. Lorrain D, Bain G, Correa L, Chapman C, Broadhead A, Santini A, et al. Pharmacological characterization of 3-[3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-5-(pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid (AM103), a novel selective 5-lipoxygenase-activating protein inhibitor that reduces a. J Pharmacol Exp Ther. 2009;331:1042-50 pubmed publisher
    ..of arachidonic acid (AA) to LTA(4) by the enzyme 5-lipoxygenase (5-LO) in the presence of 5-LO-activating protein (FLAP)...
  12. Lemaitre R, Rice K, Marciante K, Bis J, Lumley T, Wiggins K, et al. Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke. Atherosclerosis. 2009;204:e58-63 pubmed publisher
    ..TBXAS1), prostacyclin synthase (PTGIS), prostaglandin E synthase (PTGES), 5-lipoxygenase activating protein (ALOX5AP), 12-lipoxygenase (ALOX12) and 15-lipoxygenase (ALOX15) with the risks of myocardial infarction (MI) and ischemic ..
  13. Tsai A, Li N, Hanson N, Tsai M, Tang W. Associations of genetic polymorphisms of arachidonate 5-lipoxygenase-activating protein with risk of coronary artery disease in a European-American population. Atherosclerosis. 2009;207:487-91 pubmed publisher
    To examine whether genetic polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) confer an increased risk to angiographically proven coronary artery disease (CAD) in a case-control study of a Midwestern population in the US...
  14. Via M, De Giacomo A, Corvol H, Eng C, Seibold M, Gillett C, et al. The role of LTA4H and ALOX5AP genes in the risk for asthma in Latinos. Clin Exp Allergy. 2010;40:582-9 pubmed publisher
    ..and inflammatory diseases, but reports on the involvement of arachidonate 5-lipoxygenase-activating protein (ALOX5AP) and leukotriene A(4) hydrolase (LTA4H) in asthma have been inconclusive...
  15. Xu X, Sheng W, Liu Lin -. [Association between mRNA level of Pde4d and Alox5ap and hypertensive stroke as well as hypertension in rats]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007;24:491-4 pubmed
    To evaluate whether mRNA levels of Pde4d and Alox5ap were associated with hypertensive stroke and hypertension in stroke-prone renovascular hypertensive rats (RHRSP) which could simulate human being's hypertensive cerebral stroke...
  16. Fortunato G, Di Taranto M, Bracale U, Del Guercio L, Carbone F, Mazzaccara C, et al. Decreased paraoxonase-2 expression in human carotids during the progression of atherosclerosis. Arterioscler Thromb Vasc Biol. 2008;28:594-600 pubmed publisher
    ..We investigated paraoxonase 2 (PON2), 5-lipoxygenase (5-LO), and 5-LO activating protein (FLAP) expression and malondialdehyde (MDA) levels in carotid lesions to assess their involvement in plaque formation...
  17. Lorrain D, Bain G, Correa L, Chapman C, Broadhead A, Santini A, et al. Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammation. Eur J Pharmacol. 2010;640:211-8 pubmed publisher
    ..acid, a selective five-lipoxygenase-activating protein (FLAP) inhibitor, using rat and mouse models of acute inflammation...
  18. Mancini J, Abramovitz M, Cox M, Wong E, Charleson S, Perrier H, et al. 5-lipoxygenase-activating protein is an arachidonate binding protein. FEBS Lett. 1993;318:277-81 pubmed
    5-Lipoxygenase-activating protein (FLAP) is an 18-kDa integral membrane protein which is essential for cellular leukotriene (LT) synthesis, and is the target of LT biosynthesis inhibitors...
  19. Holloway J, Barton S, Holgate S, Rose Zerilli M, Sayers I. The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility. Allergy. 2008;63:1046-53 pubmed publisher
    ..Single nucleotide polymorphism (SNPs) and haplotypes spanning the LTA4H and ALOX5AP genes have been associated with LTB(4) production and myocardial infarction (MI)...
  20. Koshino T, Takano S, Kitani S, Ohshima N, Sano Y, Takaishi T, et al. Novel polymorphism of the 5-lipoxygenase activating protein (FLAP) promoter gene associated with asthma. Mol Cell Biol Res Commun. 1999;2:32-5 pubmed
    The human 5-lipoxygenase activating protein (FLAP) gene is one of the key genes involved in the production of the cysteinyl-leukotrienes...
  21. Jame A, Lackie P, Cazaly A, Sayers I, Penrose J, Holgate S, et al. Human bronchial epithelial cells express an active and inducible biosynthetic pathway for leukotrienes B4 and C4. Clin Exp Allergy. 2007;37:880-92 pubmed
    ..Constitutive mRNA and protein expression for 5-LO, 5-LO-activating protein (FLAP), LTA4 hydrolase and LTC4 synthase were demonstrated in primary HBECs and in the 16-HBE 14o- cell line...
  22. Sveinbjörnsson B, Rasmuson A, Baryawno N, Wan M, Pettersen I, Ponthan F, et al. Expression of enzymes and receptors of the leukotriene pathway in human neuroblastoma promotes tumor survival and provides a target for therapy. FASEB J. 2008;22:3525-36 pubmed publisher
    ..High expression of 5-LO, 5-LO-activating protein (FLAP), leukotriene A(4) hydrolase, leukotriene C(4) synthase, and leukotriene receptors was detected in a majority of ..
  23. Hosford G, Koyanagi K, Leung W, Olson D. Hyperoxia increases protein mass of 5-lipoxygenase and its activating protein, flap, and leukotriene B(4) output in newborn rat lungs. Exp Lung Res. 2002;28:671-84 pubmed vitro, the protein expression of the LT-synthesizing enzyme, 5-lipoxygenase (5-LO), and its activating protein (FLAP), and the effects of in vivo hyperoxic exposure (>95% O(2)) on these parameters...
  24. Chu S, Tang L, Watney E, Chi E, Henderson W. In situ amplification of 5-lipoxygenase and 5-lipoxygenase-activating protein in allergic airway inflammation and inhibition by leukotriene blockade. J Immunol. 2000;165:4640-8 pubmed
    ..situ PCR in this model of human asthma to detect lung mRNA for 5-lipoxygenase (5-LO) and 5-LO-activating protein (FLAP), key proteins necessary for leukotriene synthesis. Lung tissue was obtained on day 28 from mice treated with i.p...
  25. Kedda M, Worsley P, Shi J, Phelps S, Duffy D, Thompson P. Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population. Clin Exp Allergy. 2005;35:332-8 pubmed
    ..Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5-lipoxygenase activating protein (FLAP), and asthma...
  26. Mandal A, Jones P, Bair A, Christmas P, Miller D, Yamin T, et al. The nuclear membrane organization of leukotriene synthesis. Proc Natl Acad Sci U S A. 2008;105:20434-9 pubmed publisher
    ..We also identify these complexes in mouse neutrophils isolated from inflamed joints. Our studies reveal the macromolecular organization of LT synthesis. ..
  27. Mandal A, Skoch J, Bacskai B, Hyman B, Christmas P, Miller D, et al. The membrane organization of leukotriene synthesis. Proc Natl Acad Sci U S A. 2004;101:6587-92 pubmed
    ..One complex consists of multimers of LTC(4) synthase and the 5-lipoxygenase activating protein (FLAP). The second complex consists of multimers of FLAP...
  28. Voelkel N, Tuder R, Wade K, Hoper M, Lepley R, Goulet J, et al. Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats. J Clin Invest. 1996;97:2491-8 pubmed
    ..from the cytosol to the membrane fraction and increased levels of lung tissue 5-lipoxygenase-activating protein (FLAP)...
  29. Henderson W, Lewis D, Albert R, Zhang Y, Lamm W, Chiang G, et al. The importance of leukotrienes in airway inflammation in a mouse model of asthma. J Exp Med. 1996;184:1483-94 pubmed
    ..Specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein (FLAP) blocked airway mucus release and infiltration by eosinophils indicating a key role for leukotrienes in these ..
  30. Stanke Labesque F, Bäck M, Lefebvre B, Tamisier R, Baguet J, Arnol N, et al. Increased urinary leukotriene E4 excretion in obstructive sleep apnea: effects of obesity and hypoxia. J Allergy Clin Immunol. 2009;124:364-70, 370.e1-2 pubmed publisher
    ..Compared with baseline, CPAP reduced by 22% (P = .006) U-LTE(4) concentrations only in patients with OSA with normal BMI. Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE(4) production in patients with OSA. ..
  31. Byrum R, Goulet J, Griffiths R, Koller B. Role of the 5-lipoxygenase-activating protein (FLAP) in murine acute inflammatory responses. J Exp Med. 1997;185:1065-75 pubmed
    ..synthesis of leukotrienes, but also on expression of a nuclear membrane protein termed the 5-LO-activating protein (FLAP)...
  32. Westergren V, Wilson S, Penrose J, Howarth P, Sampson A. Nasal mucosal expression of the leukotriene and prostanoid pathways in seasonal and perennial allergic rhinitis. Clin Exp Allergy. 2009;39:820-8 pubmed publisher
    ..Enzymes of the 5-LO pathway (5-LO, FLAP, LT A4 hydrolase, LTC4 synthase) and the COX pathway (COX-1, COX-2, prostaglandin D2 synthase) were immunostained ..
  33. Seymour M, Gilby N, Bardin P, Fraenkel D, Sanderson G, Penrose J, et al. Rhinovirus infection increases 5-lipoxygenase and cyclooxygenase-2 in bronchial biopsy specimens from nonatopic subjects. J Infect Dis. 2002;185:540-4 pubmed
    ..5-LO-positive cell counts increased 9-fold (from 0.48 to 4.4 cells/mm(2); P <.05), and 5-LO-activating protein (FLAP)-positive cell counts increased 3.6-fold (from 1.8 to 6.5 cells/mm(2); P =.09)...
  34. Ferguson A, McKeever B, Xu S, Wisniewski D, Miller D, Yamin T, et al. Crystal structure of inhibitor-bound human 5-lipoxygenase-activating protein. Science. 2007;317:510-2 pubmed
    ..The integral membrane protein FLAP is essential for leukotriene biosynthesis...
  35. Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K, Watanabe S, et al. Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med. 2008;21:801-8 pubmed
    ..of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were ..
  36. Gibson C, MacLennan A, Dekker G, Goldwater P, Sullivan T, Munroe D, et al. Candidate genes and cerebral palsy: a population-based study. Pediatrics. 2008;122:1079-85 pubmed publisher
    ..Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy. ..
  37. Escoubet Lozach L, M Rini C, Rey A, Beraud M, Lepert J, Courtade M, et al. Increased expression of cytosolic phospholipase A2, 5-lipoxygenase and 5-lipoxygenase-activating protein in rat peritoneal macrophages during ovalbumin-induced sensitization. Clin Exp Allergy. 2001;31:1094-104 pubmed
    ..the expression of cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LO) and 5-lipoxygenase-activating protein (FLAP) in peritoneal macrophages during active sensitization...