Arachidonate 15-lipoxygenase

Details

Name
Arachidonate 15-lipoxygenase
Synonyms
  • 1.13.11.33
  • 12-LOX
  • 12/15-lipoxygenase
  • 15-LOX
  • Arachidonate 12-lipoxygenase, leukocyte-type
  • Arachidonate omega-6 lipoxygenase
  • LOG15
Gene Name
ALOX15
Organism
Humans
Amino acid sequence
>lcl|BSEQ0036988|Arachidonate 15-lipoxygenase
MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP
QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK
GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV
LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL
VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH
LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST
GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS
LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH
ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ
PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV
AI
Number of residues
662
Molecular Weight
74803.795
Theoretical pI
6.56
GO Classification
Functions
arachidonate 12-lipoxygenase activity / arachidonate 15-lipoxygenase activity / eoxin A4 synthase activity / hepoxilin A3 synthase activity / hepoxilin-epoxide hydrolase activity / iron ion binding / phosphatidylinositol-4,5-bisphosphate binding
Processes
apoptotic cell clearance / arachidonic acid metabolic process / bone mineralization / cellular response to calcium ion / cellular response to interleukin-13 / hepoxilin biosynthetic process / inflammatory response / leukotriene metabolic process / lipoxin A4 biosynthetic process / lipoxygenase pathway / negative regulation of adaptive immune response / ossification / phosphatidylethanolamine biosynthetic process / positive regulation of actin filament polymerization / positive regulation of cell-substrate adhesion / positive regulation of ERK1 and ERK2 cascade / positive regulation of heterotypic cell-cell adhesion / regulation of engulfment of apoptotic cell / regulation of peroxisome proliferator activated receptor signaling pathway / response to endoplasmic reticulum stress / small molecule metabolic process / wound healing
Components
cytosol / extrinsic component of cytoplasmic side of plasma membrane / lipid particle / membrane / plasma membrane
General Function
Phosphatidylinositol-4,5-bisphosphate binding
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. Converts arachidonic acid into 12-hydroperoxyeicosatetraenoic acid/12-HPETE and 15-hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010075|Arachidonate 15-lipoxygenase (ALOX15)
ATGGGTCTCTACCGCATCCGCGTGTCCACTGGGGCCTCGCTCTATGCCGGTTCCAACAAC
CAGGTGCAGCTGTGGCTGGTCGGCCAGCACGGGGAGGCGGCGCTCGGGAAGCGACTGTGG
CCCGCACGGGGCAAGGAGACAGAACTCAAGGTGGAAGTACCGGAGTATCTGGGGCCGCTG
CTGTTTGTGAAACTGCGCAAACGGCACCTCCTTAAGGACGACGCCTGGTTCTGCAACTGG
ATCTCTGTGCAGGGCCCCGGAGCCGGGGACGAGGTCAGGTTCCCTTGTTACCGCTGGGTG
GAGGGCAACGGCGTCCTGAGCCTGCCTGAAGGCACCGGCCGCACTGTGGGCGAGGACCCT
CAGGGCCTGTTCCAGAAACACCGGGAAGAAGAGCTGGAAGAGAGAAGGAAGTTGTACCGG
TGGGGAAACTGGAAGGACGGGTTAATTCTGAATATGGCTGGGGCCAAACTATATGACCTC
CCTGTGGATGAGCGATTTCTGGAAGACAAGAGAGTTGACTTTGAGGTTTCGCTGGCCAAG
GGGCTGGCCGACCTCGCTATCAAAGACTCTCTAAATGTTCTGACTTGCTGGAAGGATCTA
GATGACTTCAACCGGATTTTCTGGTGTGGTCAGAGCAAGCTGGCTGAGCGCGTGCGGGAC
TCCTGGAAGGAAGATGCCTTATTTGGGTACCAGTTTCTTAATGGCGCCAACCCCGTGGTG
CTGAGGCGCTCTGCTCACCTTCCTGCTCGCCTAGTGTTCCCTCCAGGCATGGAGGAACTG
CAGGCCCAGCTGGAGAAGGAGCTGGAGGGAGGCACACTGTTCGAAGCTGACTTCTCCCTG
CTGGATGGGATCAAGGCCAACGTCATTCTCTGTAGCCAGCAGCACCTGGCTGCCCCTCTA
GTCATGCTGAAATTGCAGCCTGATGGGAAACTCTTGCCCATGGTCATCCAGCTCCAGCTG
CCCCGCACAGGATCCCCACCACCTCCCCTTTTCTTGCCTACGGATCCCCCAATGGCCTGG
CTTCTGGCCAAATGCTGGGTGCGCAGCTCTGACTTCCAGCTCCATGAGCTGCAGTCTCAT
CTTCTGAGGGGACACTTGATGGCTGAGGTCATTGTTGTGGCCACCATGAGGTGCCTGCCG
TCGATACATCCTATCTTCAAGCTTATAATTCCCCACCTGCGATACACCCTGGAAATTAAC
GTCCGGGCCAGGACTGGGCTGGTCTCTGACATGGGAATTTTCGACCAGATAATGAGCACT
GGTGGGGGAGGCCACGTGCAGCTGCTCAAGCAAGCTGGAGCCTTCCTAACCTACAGCTCC
TTCTGTCCCCCTGATGACTTGGCCGACCGGGGGCTCCTGGGAGTGAAGTCTTCCTTCTAT
GCCCAAGATGCGCTGCGGCTCTGGGAAATCATCTATCGGTATGTGGAAGGAATCGTGAGT
CTCCACTATAAGACAGACGTGGCTGTGAAAGACGACCCAGAGCTGCAGACCTGGTGTCGA
GAGATCACTGAAATCGGGCTGCAAGGGGCCCAGGACCGAGGGTTTCCTGTCTCTTTACAG
GCTCGGGACCAGGTTTGCCACTTTGTCACCATGTGTATCTTCACCTGCACCGGCCAACAC
GCCTCTGTGCACCTGGGCCAGCTGGACTGGTACTCTTGGGTGCCTAATGCACCCTGCACG
ATGCGGCTGCCCCCGCCAACCACCAAGGATGCAACGCTGGAGACAGTGATGGCGACACTG
CCCAACTTCCACCAGGCTTCTCTCCAGATGTCCATCACTTGGCAGCTGGGCAGACGCCAG
CCCGTTATGGTGGCTGTGGGCCAGCATGAGGAGGAGTATTTTTCGGGCCCTGAGCCTAAG
GCTGTGCTGAAGAAGTTCAGGGAGGAGCTGGCTGCCCTGGATAAGGAAATTGAGATCCGG
AATGCAAAGCTGGACATGCCCTACGAGTACCTGCGGCCCAGCGTGGTGGAAAACAGTGTG
GCCATCTAA
Chromosome Location
17
Locus
17p13.3
External Identifiers
ResourceLink
UniProtKB IDP16050
UniProtKB Entry NameLOX15_HUMAN
GenBank Protein ID307135
GenBank Gene IDM23892
GenAtlas IDALOX15
HGNC IDHGNC:433
General References
  1. Sigal E, Craik CS, Highland E, Grunberger D, Costello LL, Dixon RA, Nadel JA: Molecular cloning and primary structure of human 15-lipoxygenase. Biochem Biophys Res Commun. 1988 Dec 15;157(2):457-64. [PubMed:3202857]
  2. Kritzik MR, Ziober AF, Dicharry S, Conrad DJ, Sigal E: Characterization and sequence of an additional 15-lipoxygenase transcript and of the human gene. Biochim Biophys Acta. 1997 Jun 26;1352(3):267-81. [PubMed:9224951]
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  6. Kelavkar U, Wang S, Montero A, Murtagh J, Shah K, Badr K: Human 15-lipoxygenase gene promoter: analysis and identification of DNA binding sites for IL-13-induced regulatory factors in monocytes. Mol Biol Rep. 1998 Jul;25(3):173-82. [PubMed:9700053]
  7. Sigal E, Grunberger D, Craik CS, Caughey GH, Nadel JA: Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. Purification and structural homology to other mammalian lipoxygenases. J Biol Chem. 1988 Apr 15;263(11):5328-32. [PubMed:3356688]
  8. Izumi T, Radmark O, Jornvall H, Samuelsson B: Purification of two forms of arachidonate 15-lipoxygenase from human leukocytes. Eur J Biochem. 1991 Dec 18;202(3):1231-8. [PubMed:1662607]
  9. Sloane DL, Leung R, Craik CS, Sigal E: A primary determinant for lipoxygenase positional specificity. Nature. 1991 Nov 14;354(6349):149-52. [PubMed:1944593]
  10. Brinckmann R, Schnurr K, Heydeck D, Rosenbach T, Kolde G, Kuhn H: Membrane translocation of 15-lipoxygenase in hematopoietic cells is calcium-dependent and activates the oxygenase activity of the enzyme. Blood. 1998 Jan 1;91(1):64-74. [PubMed:9414270]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08492(2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACIDexperimentalunknownDetails
DB02709ResveratrolinvestigationalunknownDetails
DB09061Cannabidiolapproved, investigationalunknowninhibitorDetails
DB14011NabiximolsinvestigationalunknowninhibitorDetails
DB14009Medical Cannabisexperimental, investigationalunknowninhibitorDetails