Arachidonate 5-lipoxygenase

Details

Name
Arachidonate 5-lipoxygenase
Synonyms
  • 1.13.11.34
  • 5-LO
  • LOG5
Gene Name
ALOX5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036979|Arachidonate 5-lipoxygenase
MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDE
ELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLA
RDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL
NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNG
CNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDP
CTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF
HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECG
LFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWE
AIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYL
TVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCW
HLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPY
YYLSPDRIPNSVAI
Number of residues
674
Molecular Weight
77982.595
Theoretical pI
5.54
GO Classification
Functions
arachidonate 5-lipoxygenase activity / iron ion binding
Processes
acute inflammatory response / arachidonic acid metabolic process / leukotriene biosynthetic process / leukotriene metabolic process / leukotriene production involved in inflammatory response / lipoxin metabolic process / lipoxygenase pathway / positive regulation of vasoconstriction / response to hyperoxia / response to nutrient / sensory perception of pain / small molecule metabolic process
Components
cytosol / dendrite / extracellular space / nuclear envelope / nuclear envelope lumen / nuclear matrix / nuclear membrane / sarcolemma
General Function
Iron ion binding
Specific Function
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010032|Arachidonate 5-lipoxygenase (ALOX5)
ATGCCCTCCTACACGGTCACCGTGGCCACTGGCAGCCAGTGGTTCGCCGGCACTGACGAC
TACATCTACCTCAGCCTCGTGGGCTCGGCGGGCTGCAGCGAGAAGCACCTGCTGGACAAG
CCCTTCTACAACGACTTCGAGCGTGGCGCGGTGGATTCATACGACGTGACTGTGGACGAG
GAACTGGGCGAGATCCAGCTGGTCAGAATCGAGAAGCGCAAGTACTGGCTGAATGACGAC
TGGTACCTGAAGTACATCACGCTGAAGACGCCCCACGGGGACTACATCGAGTTCCCCTGC
TACCGCTGGATCACCGGCGATGTCGAGGTTGTCCTGAGGGATGGACGCGCAAAGTTGGCC
CGAGATGACCAAATTCACATTCTCAAGCAACACCGACGTAAAGAACTGGAAACACGGCAA
AAACAATATCGATGGATGGAGTGGAACCCTGGCTTCCCCTTGAGCATCGATGCCAAATGC
CACAAGGATTTACCCCGTGATATCCAGTTTGATAGTGAAAAAGGAGTGGACTTTGTTCTG
AATTACTCCAAAGCGATGGAGAACCTGTTCATCAACCGCTTCATGCACATGTTCCAGTCT
TCTTGGAATGACTTCGCCGACTTTGAGAAAATCTTTGTCAAGATCAGCAACACTATTTCT
GAGCGGGTCATGAATCACTGGCAGGAAGACCTGATGTTTGGCTACCAGTTCCTGAATGGC
TGCAACCCTGTGTTGATCCGGCGCTGCACAGAGCTGCCCGAGAAGCTCCCGGTGACCACG
GAGATGGTAGAGTGCAGCCTGGAGCGGCAGCTCAGCTTGGAGCAGGAGGTCCAGCAAGGG
AACATTTTCATCGTGGACTTTGAGCTGCTGGATGGCATCGATGCCAACAAAACAGACCCC
TGCACACTCCAGTTCCTGGCCGCTCCCATCTGCTTGCTGTATAAGAACCTGGCCAACAAG
ATTGTCCCCATTGCCATCCAGCTCAACCAAATCCCGGGAGATGAGAACCCTATTTTCCTC
CCTTCGGATGCAAAATACGACTGGCTTTTGGCCAAAATCTGGGTGCGTTCCAGTGACTTC
CACGTCCACCAGACCATCACCCACCTTCTGCGAACACATCTGGTGTCTGAGGTTTTTGGC
ATTGCAATGTACCGCCAGCTGCCTGCTGTGCACCCCATTTTCAAGCTGCTGGTGGCACAC
GTGAGATTCACCATTGCAATCAACACCAAGGCCCGTGAGCAGCTCATCTGCGAGTGTGGC
CTCTTTGACAAGGCCAACGCCACAGGGGGCGGTGGGCACGTGCAGATGGTGCAGAGGGCC
ATGAAGGACCTGACCTATGCCTCCCTGTGCTTTCCCGAGGCCATCAAGGCCCGGGGCATG
GAGAGCAAAGAAGACATCCCCTACTACTTCTACCGGGACGACGGGCTCCTGGTGTGGGAA
GCCATCAGGACGTTCACGGCCGAGGTGGTAGACATCTACTACGAGGGCGACCAGGTGGTG
GAGGAGGACCCGGAGCTGCAGGACTTCGTGAACGATGTCTACGTGTACGGCATGCGGGGC
CGCAAGTCCTCAGGCTTCCCCAAGTCGGTCAAGAGCCGGGAGCAGCTGTCGGAGTACCTG
ACCGTGGTGATCTTCACCGCCTCCGCCCAGCACGCCGCGGTCAACTTCGGCCAGTACGAC
TGGTGCTCCTGGATCCCCAATGCGCCCCCAACCATGCGAGCCCCGCCACCGACTGCCAAG
GGCGTGGTGACCATTGAGCAGATCGTGGACACGCTGCCCGACCGCGGCCGCTCCTGCTGG
CATCTGGGTGCAGTGTGGGCGCTGAGCCAGTTCCAGGAAAACGAGCTGTTCCTGGGCATG
TACCCAGAAGAGCATTTTATCGAGAAGCCTGTGAAGGAAGCCATGGCCCGATTCCGCAAG
AACCTCGAGGCCATTGTCAGCGTGATTGCTGAGCGCAACAAGAAGAAGCAGCTGCCATAT
TACTACTTGTCCCCAGACCGGATTCCGAACAGTGTGGCCATCTGA
Chromosome Location
10
Locus
10q11.2
External Identifiers
ResourceLink
UniProtKB IDP09917
UniProtKB Entry NameLOX5_HUMAN
GenBank Protein ID187193
GenBank Gene IDJ03600
GenAtlas IDALOX5
HGNC IDHGNC:435
General References
  1. Dixon RA, Jones RE, Diehl RE, Bennett CD, Kargman S, Rouzer CA: Cloning of the cDNA for human 5-lipoxygenase. Proc Natl Acad Sci U S A. 1988 Jan;85(2):416-20. [PubMed:3422434]
  2. Matsumoto T, Funk CD, Radmark O, Hoog JO, Jornvall H, Samuelsson B: Molecular cloning and amino acid sequence of human 5-lipoxygenase. Proc Natl Acad Sci U S A. 1988 Jan;85(1):26-30. [PubMed:2829172]
  3. Matsumoto T, Funk CD, Radmark O, Hoog JO, Jornvall H, Samuelsson B: Molecular cloning and amino acid sequence of human 5-lipoxygenase. Adv Prostaglandin Thromboxane Leukot Res. 1989;19:466-9. [PubMed:2526519]
  4. Boudreau LH, Bertin J, Robichaud PP, Laflamme M, Ouellette RJ, Flamand N, Surette ME: Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products. FASEB J. 2011 Mar;25(3):1097-105. doi: 10.1096/fj.10-173856. Epub 2010 Nov 23. [PubMed:21098726]
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  6. 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]
  7. Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B: Characterization of the human 5-lipoxygenase gene. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2587-91. [PubMed:2565035]
  8. Hoshiko S, Radmark O, Samuelsson B: Characterization of the human 5-lipoxygenase gene promoter. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9073-7. [PubMed:2251250]
  9. Rouzer CA, Samuelsson B: Reversible, calcium-dependent membrane association of human leukocyte 5-lipoxygenase. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7393-7. [PubMed:3118366]
  10. Nguyen T, Falgueyret JP, Abramovitz M, Riendeau D: Evaluation of the role of conserved His and Met residues among lipoxygenases by site-directed mutagenesis of recombinant human 5-lipoxygenase. J Biol Chem. 1991 Nov 15;266(32):22057-62. [PubMed:1939225]
  11. Ishii S, Noguchi M, Miyano M, Matsumoto T, Noma M: Mutagenesis studies on the amino acid residues involved in the iron-binding and the activity of human 5-lipoxygenase. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1482-90. [PubMed:1540191]
  12. Woods JW, Evans JF, Ethier D, Scott S, Vickers PJ, Hearn L, Heibein JA, Charleson S, Singer II: 5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes. J Exp Med. 1993 Dec 1;178(6):1935-46. [PubMed:8245774]
  13. Werz O, Szellas D, Steinhilber D, Radmark O: Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). J Biol Chem. 2002 Apr 26;277(17):14793-800. Epub 2002 Feb 13. [PubMed:11844797]
  14. Luo M, Jones SM, Phare SM, Coffey MJ, Peters-Golden M, Brock TG: Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5-lipoxygenase on serine 523. J Biol Chem. 2004 Oct 1;279(40):41512-20. Epub 2004 Jul 26. [PubMed:15280375]
  15. Flamand N, Lefebvre J, Surette ME, Picard S, Borgeat P: Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. J Biol Chem. 2006 Jan 6;281(1):129-36. Epub 2005 Nov 7. [PubMed:16275640]
  16. Strid T, Svartz J, Franck N, Hallin E, Ingelsson B, Soderstrom M, Hammarstrom S: Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein. Biochem Biophys Res Commun. 2009 Apr 17;381(4):518-22. doi: 10.1016/j.bbrc.2009.02.074. Epub 2009 Feb 20. [PubMed:19233132]
  17. Flamand N, Luo M, Peters-Golden M, Brock TG: Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export. J Biol Chem. 2009 Jan 2;284(1):306-13. doi: 10.1074/jbc.M805593200. Epub 2008 Nov 1. [PubMed:18978352]
  18. Esser J, Rakonjac M, Hofmann B, Fischer L, Provost P, Schneider G, Steinhilber D, Samuelsson B, Radmark O: Coactosin-like protein functions as a stabilizing chaperone for 5-lipoxygenase: role of tryptophan 102. Biochem J. 2009 Dec 14;425(1):265-74. doi: 10.1042/BJ20090856. [PubMed:19807693]
  19. Gilbert NC, Bartlett SG, Waight MT, Neau DB, Boeglin WE, Brash AR, Newcomer ME: The structure of human 5-lipoxygenase. Science. 2011 Jan 14;331(6014):217-9. doi: 10.1126/science.1197203. [PubMed:21233389]
  20. Goodman JE, Bowman ED, Chanock SJ, Alberg AJ, Harris CC: Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. Carcinogenesis. 2004 Dec;25(12):2467-72. Epub 2004 Aug 12. [PubMed:15308583]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00711Diethylcarbamazineapproved, investigational, vet_approvedyesinhibitorDetails
DB00471Montelukastapprovedunknownother/unknownDetails
DB00744Zileutonapproved, investigational, withdrawnyesinhibitorDetails
DB00939Meclofenamic acidapproved, vet_approvedyesinhibitorDetails
DB01017Minocyclineapproved, investigationalunknowninhibitorDetails
DB01892HyperforinnutraceuticalunknowninhibitorDetails
DB04725LicofeloneinvestigationalunknownDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknownDetails
DB00179Masoprocolapproved, investigationalyesinhibitorDetails
DB05431MLN-977investigationalunknownDetails
DB01014Balsalazideapproved, investigationalyesinhibitorDetails
DB00244MesalazineapprovedyesinhibitorDetails
DB00795SulfasalazineapprovedyesinhibitorDetails
DB00233Aminosalicylic AcidapprovedunknowninhibitorDetails
DB00586Diclofenacapproved, vet_approvedyespotentiatorDetails
DB13174RheinexperimentalunknowninhibitorDetails
DB11994Diacereinapproved, investigationalunknowninhibitorDetails
DB11133Omega-3 fatty acidsapproved, nutraceuticalunknownsubstrateDetails
DB13168Omega-6 fatty acidsnutraceuticalunknownsubstrateDetails
DB02709Resveratrolapproved, experimental, investigationalunknownDetails
DB09061Cannabidiolapproved, investigationalunknowninhibitorDetails
DB09285MorniflumateexperimentalunknownantagonistDetails
DB09285MorniflumateexperimentalunknowninhibitorDetails
DB14001alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknownDetails
DB14002D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknownDetails
DB14011NabiximolsinvestigationalunknowninhibitorDetails
DB14009Medical Cannabisexperimental, investigationalunknowninhibitorDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails