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Gene Review

ALOX5  -  arachidonate 5-lipoxygenase

Homo sapiens

Synonyms: 5-LO, 5-LOX, 5-lipoxygenase, 5LPG, Arachidonate 5-lipoxygenase, ...
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Disease relevance of ALOX5

  • Furthermore, an inverse association was observed between A alleles at positions -1752 and -1699 of ALOX5 and colon cancer risk in Caucasians, but not in African-Americans [1].
  • Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population [2].
  • Prevention of thrombosis and vascular inflammation: benefits and limitations of selective or combined COX-1, COX-2 and 5-LOX inhibitors [3].
  • Recently we showed that levels of 5-lipoxygenase (5-LOX)-derived proinflammatory/profibrotic leukotrienes are elevated in bronchoalveolar lavage (BAL) fluid from patients with scleroderma lung disease (SLD) [4].
  • Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps of patients with aspirin-intolerant asthma [5].

Psychiatry related information on ALOX5


High impact information on ALOX5


Chemical compound and disease context of ALOX5


Biological context of ALOX5


Anatomical context of ALOX5

  • Here we describe that activation of p38 mitogen-activated protein kinase in human polymorphonuclear leukocytes and in Mono Mac 6 cells leads to activation of downstream kinases, which can subsequently phosphorylate 5-LO in vitro [18].
  • Cell splitting of the Epstein-Barr virus-transformed B lymphocytic cell line BL41-E95-A caused a pronounced, but transient, reduction of functional 5-LO protein, accompanied by the appearance of a 62-kDa 5-LO cleavage product [19].
  • The LC 5-LO protein was largely found in the nuclear matrix, in nuclear envelopes, and perinuclear regions as indicated by in situ confocal laser scan microscopy [20].
  • Immunohistochemical staining revealed abundant expression of 5-LO, FLAP, and LTA4H protein, colocalizing in macrophages of intimal lesions [21].
  • 5-Lipoxygenase expression in Langerhans cells of normal human epidermis [20].

Associations of ALOX5 with chemical compounds

  • However, there was a strong association of the ALOX5 Sp1 repeat polymorphism with airway hyperresponsiveness (AHR; PC20 methacholine); AIA patients carrying a mutant allele (n > 5 or n < 5 repeats) showed increased AHR compared to AIA patients with wild-type genotype (P=0.003) [22].
  • 5-Lipoxygenase (5-LO) is a tightly regulated enzyme in the synthesis of bioactive lipids from arachidonic acid [19].
  • Enriched primary LCs were also found to contain 5-LO activating protein (FLAP), leukotriene (LT) C4 synthase, and LTA4 hydrolase [20].
  • Furthermore, expression of 5-LO and LTA4H, but not FLAP, is increased in patients with recent or ongoing symptoms of plaque instability, and medication with warfarin correlates with increased levels of FLAP mRNA [21].
  • For all stimuli, 5-LO kinase activation was counteracted by SB203580 (3 microM or less), an inhibitor of p38 kinase [18].

Physical interactions of ALOX5

  • Non-denaturing polyacrylamide gel electrophoresis and cross-linking experiments showed that 5LO binds CLP in a 1:1 molar stoichiometry in a Ca(2+)-independent manner [23].
  • 5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins [24].
  • These results implicate that compounds that bind competitively to arachidonic acid binding sites on FLAP and 5-LO recognize motifs that are also weakly conserved on the binding site of LTC4 synthase [25].
  • Here, we report that a response element in the promoter of 5-lipoxygenase binds specifically RZR alpha and ROR alpha 1, but not ROR alpha 2 and alpha 3 [26].
  • Once imported into the resting and/or activated leukocytes, AA derived from the S100A8/A9+AA complex could serve as a substrate in the 5-lipoxygenase-mediated leukotriene pathway [27].

Enzymatic interactions of ALOX5


Regulatory relationships of ALOX5


Other interactions of ALOX5


Analytical, diagnostic and therapeutic context of ALOX5


  1. Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. Goodman, J.E., Bowman, E.D., Chanock, S.J., Alberg, A.J., Harris, C.C. Carcinogenesis (2004) [Pubmed]
  2. Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population. Kim, S.H., Choi, J.H., Holloway, J.W., Suh, C.H., Nahm, D.H., Ha, E.H., Park, C.S., Park, H.S. J. Korean Med. Sci. (2005) [Pubmed]
  3. Prevention of thrombosis and vascular inflammation: benefits and limitations of selective or combined COX-1, COX-2 and 5-LOX inhibitors. de Gaetano, G., Donati, M.B., Cerletti, C. Trends Pharmacol. Sci. (2003) [Pubmed]
  4. Cyclooxygenase- and lipoxygenase-derived eicosanoids in bronchoalveolar lavage fluid from patients with scleroderma lung disease: an imbalance between proinflammatory and antiinflammatory lipid mediators. Kowal-Bielecka, O., Kowal, K., Distler, O., Rojewska, J., Bodzenta-Lukaszyk, A., Michel, B.A., Gay, R.E., Gay, S., Sierakowski, S. Arthritis Rheum. (2005) [Pubmed]
  5. Expression of 5-lipoxygenase and cyclooxygenase pathway enzymes in nasal polyps of patients with aspirin-intolerant asthma. Adamjee, J., Suh, Y.J., Park, H.S., Choi, J.H., Penrose, J.F., Lam, B.K., Austen, K.F., Cazaly, A.M., Wilson, S.J., Sampson, A.P. J. Pathol. (2006) [Pubmed]
  6. 5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and Alzheimer's disease. Manev, H., Manev, R. Med. Hypotheses (2006) [Pubmed]
  7. Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase. Nguyen, T., Falgueyret, J.P., Abramovitz, M., Riendeau, D. J. Biol. Chem. (1991) [Pubmed]
  8. A taurine-supplemented vegan diet may blunt the contribution of neutrophil activation to acute coronary events. McCarty, M.F. Med. Hypotheses (2004) [Pubmed]
  9. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Helgadottir, A., Manolescu, A., Thorleifsson, G., Gretarsdottir, S., Jonsdottir, H., Thorsteinsdottir, U., Samani, N.J., Gudmundsson, G., Grant, S.F., Thorgeirsson, G., Sveinbjornsdottir, S., Valdimarsson, E.M., Matthiasson, S.E., Johannsson, H., Gudmundsdottir, O., Gurney, M.E., Sainz, J., Thorhallsdottir, M., Andresdottir, M., Frigge, M.L., Topol, E.J., Kong, A., Gudnason, V., Hakonarson, H., Gulcher, J.R., Stefansson, K. Nat. Genet. (2004) [Pubmed]
  10. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Drazen, J.M., Yandava, C.N., Dubé, L., Szczerback, N., Hippensteel, R., Pillari, A., Israel, E., Schork, N., Silverman, E.S., Katz, D.A., Drajesk, J. Nat. Genet. (1999) [Pubmed]
  11. Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis. Chen, X., Wang, S., Wu, N., Sood, S., Wang, P., Jin, Z., Beer, D.G., Giordano, T.J., Lin, Y., Shih, W.C., Lubet, R.A., Yang, C.S. Clin. Cancer Res. (2004) [Pubmed]
  12. 5-Lipoxygenase inhibitors: synthesis and structure-activity relationships of a series of 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-ones. Bhatia, P.A., Brooks, C.D., Basha, A., Ratajczyk, J.D., Gunn, B.P., Bouska, J.B., Lanni, C., Young, P.R., Bell, R.L., Carter, G.W. J. Med. Chem. (1996) [Pubmed]
  13. Safety of anti-inflammatory treatment--new ways of thinking. Brune, K. Rheumatology (Oxford, England) (2004) [Pubmed]
  14. Inhibition of 5-lipoxygenase by MK886 augments the antitumor activity of celecoxib in human colon cancer cells. Cianchi, F., Cortesini, C., Magnelli, L., Fanti, E., Papucci, L., Schiavone, N., Messerini, L., Vannacci, A., Capaccioli, S., Perna, F., Lulli, M., Fabbroni, V., Perigli, G., Bechi, P., Masini, E. Mol. Cancer Ther. (2006) [Pubmed]
  15. Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Lima, J.J., Zhang, S., Grant, A., Shao, L., Tantisira, K.G., Allayee, H., Wang, J., Sylvester, J., Holbrook, J., Wise, R., Weiss, S.T., Barnes, K. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  16. Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. Sayers, I., Barton, S., Rorke, S., Sawyer, J., Peng, Q., Beghé, B., Ye, S., Keith, T., Clough, J.B., Holloway, J.W., Sampson, A.P., Holgate, S.T. Clin. Exp. Allergy (2003) [Pubmed]
  17. Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase. Choi, J.H., Park, H.S., Oh, H.B., Lee, J.H., Suh, Y.J., Park, C.S., Shin, H.D. Hum. Genet. (2004) [Pubmed]
  18. 5-lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases. Werz, O., Klemm, J., Samuelsson, B., Rådmark, O. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  19. Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cells. Werz, O., Tretiakova, I., Michel, A., Ulke-Lemee, A., Hörnig, M., Franke, L., Schneider, G., Samuelsson, B., Rådmark, O., Steinhilber, D. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  20. 5-Lipoxygenase expression in Langerhans cells of normal human epidermis. Spanbroek, R., Stark, H.J., Janssen-Timmen, U., Kraft, S., Hildner, M., Andl, T., Bosch, F.X., Fusenig, N.E., Bieber, T., Rådmark, O., Samuelsson, B., Habenicht, A.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  21. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Qiu, H., Gabrielsen, A., Agardh, H.E., Wan, M., Wetterholm, A., Wong, C.H., Hedin, U., Swedenborg, J., Hansson, G.K., Samuelsson, B., Paulsson-Berne, G., Haeggström, J.Z. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  22. Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness. Kim, S.H., Bae, J.S., Suh, C.H., Nahm, D.H., Holloway, J.W., Park, H.S. Allergy (2005) [Pubmed]
  23. 5-Lipoxygenase interacts with coactosin-like protein. Provost, P., Doucet, J., Hammarberg, T., Gerisch, G., Samuelsson, B., Radmark, O. J. Biol. Chem. (2001) [Pubmed]
  24. 5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and cytoskeletal proteins. Lepley, R.A., Fitzpatrick, F.A. J. Biol. Chem. (1994) [Pubmed]
  25. Pharmacological cross-reactivity between 5-lipoxygenase-activating protein, 5-lipoxygenase, and leukotriene C4 synthase. Gupta, N., Nicholson, D.W., Ford-Hutchinson, A.W. Can. J. Physiol. Pharmacol. (1997) [Pubmed]
  26. The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. Steinhilber, D., Brungs, M., Werz, O., Wiesenberg, I., Danielsson, C., Kahlen, J.P., Nayeri, S., Schräder, M., Carlberg, C. J. Biol. Chem. (1995) [Pubmed]
  27. Inflammation: a novel mechanism for the transport of extracellular nucleotide-induced arachidonic acid by S100A8/A9 for transcellular metabolism. Kannan, S. Cell Biol. Int. (2003) [Pubmed]
  28. Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-Jun N-terminal kinase. Ghosh, J. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  29. 5-Lipoxygenase and 5-lipoxygenase activating protein (FLAP) immunoreactivity in lungs from patients with primary pulmonary hypertension. Wright, L., Tuder, R.M., Wang, J., Cool, C.D., Lepley, R.A., Voelkel, N.F. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  30. Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes. Jakobsson, P.J., Shaskin, P., Larsson, P., Feltenmark, S., Odlander, B., Aguilar-Santelises, M., Jondal, M., Biberfeld, P., Claesson, H.E. Eur. J. Biochem. (1995) [Pubmed]
  31. Selenium-dependent peroxidases suppress 5-lipoxygenase activity in B-lymphocytes and immature myeloid cells. The presence of peroxidase-insensitive 5-lipoxygenase activity in differentiated myeloid cells. Werz, O., Steinhilber, D. Eur. J. Biochem. (1996) [Pubmed]
  32. Interaction of 5-lipoxygenase with cellular proteins. Provost, P., Samuelsson, B., Rådmark, O. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  33. The C2-like beta-barrel domain mediates the Ca2+-dependent resistance of 5-lipoxygenase activity against inhibition by glutathione peroxidase-1. Bürkert, E., Arnold, C., Hammarberg, T., Rådmark, O., Steinhilber, D., Werz, O. J. Biol. Chem. (2003) [Pubmed]
  34. Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). Werz, O., Szellas, D., Steinhilber, D., Rådmark, O. J. Biol. Chem. (2002) [Pubmed]
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