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Showing Protein Polyunsaturated fatty acid lipoxygenase ALOX8 (HMDBP13375)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP13375
Secondary Accession Numbers None
Name Polyunsaturated fatty acid lipoxygenase ALOX8
Synonyms
  1. 15-lipoxygenase 2
  2. Arachidonate 15-lipoxygenase B
  3. Arachidonate 8S-lipoxygenase
  4. Linoleate 9S-lipoxygenase ALOX8
  5. 15-LOX-2
  6. 15-LOX-B
  7. 8-LOX
  8. 8S-LOX
Gene Name ALOX8
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). Catalyzes the peroxidation of arachidonate and linoleate into (8S)-HPETE and (9S)-HPODE respectively (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). In addition to generate (8S)-HPETE from free arachidonic acid (AA), may produce other HETE isomers from phospholipid-esterified polyunsaturated fatty acids and minor products derived from (8S)-HPETE itself that may include leukotriene A4 and 8,15-diHPETE (PubMed:16143298, PubMed:16112079, PubMed:27435673). With free arachidonate as substrate, has no detectable 15S-lipoxygenase activity and only displays a 8S-lipoxygenase activity (PubMed:10625675, PubMed:16112079, PubMed:16143298, PubMed:15558016, PubMed:10965849, PubMed:9305900). However may have a 15S-lipoxygenase activity with (8S)-HPETE to produce (8S,15S)-diHPETE and when oxidizes directly arachidonic acid esterified to membrane-bound phospholipids to produce a phospholipid-esterified 15-HpETE (PubMed:27435673, PubMed:16112079, PubMed:16143298). May also catalyze (15S)-HPETE peroxidation to produce 8,15-diHPETE (PubMed:16112079). May play a role in keratinocyte differentiation through activation of the peroxisome proliferator activated receptor signaling pathway (PubMed:10965849).
Pathways
  • Arachidonic acid metabolism
  • hydroperoxy eicosatetraenoic acid biosynthesis
  • Serotonergic synapse
Reactions Not Available
GO Classification
Biological Process
negative regulation of growth
positive regulation of chemokine production
lipoxin A4 biosynthetic process
hepoxilin biosynthetic process
endocannabinoid signaling pathway
cannabinoid biosynthetic process
positive regulation of peroxisome proliferator activated receptor signaling pathway
lipid oxidation
lipoxygenase pathway
positive regulation of macrophage derived foam cell differentiation
negative regulation of cell cycle
arachidonic acid metabolic process
lipid metabolic process
phospholipid metabolic process
linoleic acid metabolic process
negative regulation of cell proliferation
positive regulation of keratinocyte differentiation
Cellular Component
adherens junction
plasma membrane
membrane
cytoskeleton
cytosol
focal adhesion
extrinsic to membrane
Molecular Function
arachidonate 15-lipoxygenase activity
lipoxygenase activity
lipid binding
iron ion binding
arachidonate 8(S)-lipoxygenase activity
linoleate 9S-lipoxygenase activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
calcium ion binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 677
Molecular Weight 76229.68
Theoretical pI 6.73
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O35936
UniProtKB/Swiss-Prot Entry Name ALOX8_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. [PubMed:16141072 ]
  3. Jisaka M, Iwanaga C, Takahashi N, Goto T, Kawada T, Yamamoto T, Ikeda I, Nishimura K, Nagaya T, Fushiki T, Yokota K: Double dioxygenation by mouse 8S-lipoxygenase: specific formation of a potent peroxisome proliferator-activated receptor alpha agonist. Biochem Biophys Res Commun. 2005 Dec 9;338(1):136-43. Epub 2005 Aug 15. [PubMed:16112079 ]
  4. Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26. [PubMed:19468303 ]
  5. Jisaka M, Kim RB, Boeglin WE, Nanney LB, Brash AR: Molecular cloning and functional expression of a phorbol ester-inducible 8S-lipoxygenase from mouse skin. J Biol Chem. 1997 Sep 26;272(39):24410-6. doi: 10.1074/jbc.272.39.24410. [PubMed:9305900 ]
  6. Krieg P, Kinzig A, Heidt M, Marks F, Furstenberger G: cDNA cloning of a 8-lipoxygenase and a novel epidermis-type lipoxygenase from phorbol ester-treated mouse skin. Biochim Biophys Acta. 1998 Mar 6;1391(1):7-12. doi: 10.1016/s0005-2760(97)00214-2. [PubMed:9518531 ]
  7. Muga SJ, Thuillier P, Pavone A, Rundhaug JE, Boeglin WE, Jisaka M, Brash AR, Fischer SM: 8S-lipoxygenase products activate peroxisome proliferator-activated receptor alpha and induce differentiation in murine keratinocytes. Cell Growth Differ. 2000 Aug;11(8):447-54. [PubMed:10965849 ]
  8. Jisaka M, Kim RB, Boeglin WE, Brash AR: Identification of amino acid determinants of the positional specificity of mouse 8S-lipoxygenase and human 15S-lipoxygenase-2. J Biol Chem. 2000 Jan 14;275(2):1287-93. doi: 10.1074/jbc.275.2.1287. [PubMed:10625675 ]
  9. Jisaka M, Boeglin WE, Kim RB, Brash AR: Site-directed mutagenesis studies on a putative fifth iron ligand of mouse 8S-lipoxygenase: retention of catalytic activity on mutation of serine-558 to asparagine, histidine, or alanine. Arch Biochem Biophys. 2001 Feb 15;386(2):136-42. doi: 10.1006/abbi.2000.2175. [PubMed:11368335 ]
  10. Kawajiri H, Piao Y, Takahashi Y, Murakami T, Hamanaka N, Yoshimoto T: Synthesis of 8,9-leukotriene A4 by murine 8-lipoxygenase. Biochem Biophys Res Commun. 2005 Dec 9;338(1):144-8. doi: 10.1016/j.bbrc.2005.08.099. Epub 2005 Aug 24. [PubMed:16143298 ]
  11. Kim E, Rundhaug JE, Benavides F, Yang P, Newman RA, Fischer SM: An antitumorigenic role for murine 8S-lipoxygenase in skin carcinogenesis. Oncogene. 2005 Feb 10;24(7):1174-87. doi: 10.1038/sj.onc.1208269. [PubMed:15558016 ]
  12. Bender G, Schexnaydre EE, Murphy RC, Uhlson C, Newcomer ME: Membrane-dependent Activities of Human 15-LOX-2 and Its Murine Counterpart: IMPLICATIONS FOR MURINE MODELS OF ATHEROSCLEROSIS. J Biol Chem. 2016 Sep 9;291(37):19413-24. doi: 10.1074/jbc.M116.741454. Epub 2016 Jul 19. [PubMed:27435673 ]