Arachidonate 12-lipoxygenase, 12S-type

NameArachidonate 12-lipoxygenase, 12S-type
Synonyms
  • 1.13.11.31
  • 12LO
  • 12S-LOX
  • Lipoxin synthase 12-LO
  • LOG12
  • Platelet-type lipoxygenase 12
Gene NameALOX12
OrganismHuman
Amino acid sequence
>lcl|BSEQ0017198|Arachidonate 12-lipoxygenase, 12S-type
MGRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLL
QFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEGTARLPGDNA
LDMFQKHREKELKDRQQIYCWATWKEGLPLTIAADRKDDLPPNMRFHEEKRLDFEWTLKA
GALEMALKRVYTLLSSWNCLEDFDQIFWGQKSALAEKVRQCWQDDELFSYQFLNGANPML
LRRSTSLPSRLVLPSGMEELQAQLEKELQNGSLFEADFILLDGIPANVIRGEKQYLAAPL
VMLKMEPNGKLQPMVIQIQPPNPSSPTPTLFLPSDPPLAWLLAKSWVRNSDFQLHEIQYH
LLNTHLVAEVIAVATMRCLPGLHPIFKFLIPHIRYTMEINTRARTQLISDGGIFDKAVST
GGGGHVQLLRRAAAQLTYCSLCPPDDLADRGLLGLPGALYAHDALRLWEIIARYVEGIVH
LFYQRDDIVKGDPELQAWCREITEVGLCQAQDRGFPVSFQSQSQLCHFLTMCVFTCTAQH
AAINQGQLDWYAWVPNAPCTMRMPPPTTKEDVTMATVMGSLPDVRQACLQMAISWHLSRR
QPDMVPLGHHKEKYFSGPKPKAVLNQFRTDLEKLEKEITARNEQLDWPYEYLKPSCIENS
VTI
Number of residues663
Molecular Weight75693.38
Theoretical pI6.15
GO Classification
Functions
  • iron ion binding
  • oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
  • linoleate 13S-lipoxygenase activity
  • arachidonate 12-lipoxygenase activity
  • hepoxilin A3 synthase activity
  • hepoxilin-epoxide hydrolase activity
Processes
  • positive regulation of endothelial cell differentiation
  • movement of cell or subcellular component
  • positive regulation of cell adhesion
  • positive regulation of endothelial cell migration
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
  • negative regulation of muscle cell apoptotic process
  • positive regulation of smooth muscle cell proliferation
  • linoleic acid metabolic process
  • positive regulation of angiogenesis
  • positive regulation of mitochondrial depolarization
  • arachidonic acid metabolic process
  • negative regulation of platelet aggregation
  • lipoxin metabolic process
  • fatty acid oxidation
  • establishment of skin barrier
  • lipoxygenase pathway
  • reactive oxygen species metabolic process
  • positive regulation of gene expression
  • small molecule metabolic process
  • superoxide anion generation
  • aging
  • cellular response to lipid
  • hepoxilin metabolic process
  • positive regulation of cell migration
  • leukotriene A4 metabolic process
  • hepoxilin biosynthetic process
  • negative regulation of apoptotic process
  • lipoxin B4 biosynthetic process
  • lipoxin A4 biosynthetic process
  • positive regulation of cell growth
  • positive regulation of vasodilation
  • positive regulation of cell proliferation
Components
  • sarcolemma
  • cytoplasm
  • membrane
  • cytosol
  • extracellular exosome
General FunctionOxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
Specific FunctionNon-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Mainly converts arachidonic acid to (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID189774
UniProtKB IDP18054
UniProtKB Entry NameLOX12_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0017199|Arachidonate 12-lipoxygenase, 12S-type (ALOX12)
ATGGGCCGCTACCGCATCCGCGTGGCCACCGGGGCCTGGCTCTTCTCCGGGTCGTACAAC
CGCGTGCAGCTTTGGCTGGTCGGGACGCGCGGGGAGGCGGAGCTGGAGCTGCAGCTGCGG
CCCGCGCGGGGCGAGGAGGAGGAGTTTGATCATGACGTTGCAGAGGACTTGGGGCTCCTG
CAGTTCGTGAGGCTGCGCAAGCACCACTGGCTGGTGGACGACGCGTGGTTCTGCGACCGC
ATCACGGTGCAGGGCCCTGGAGCCTGCGCGGAGGTGGCCTTCCCGTGCTACCGCTGGGTG
CAGGGCGAGGACATCCTGAGCCTGCCCGAGGGCACCGCCCGCCTGCCAGGAGACAATGCT
TTGGACATGTTCCAGAAGCATCGAGAGAAGGAACTGAAAGACAGACAGCAGATCTACTGC
TGGGCCACCTGGAAGGAAGGGTTACCCCTGACCATCGCTGCAGACCGTAAGGATGATCTA
CCTCCAAATATGAGATTCCATGAGGAGAAGAGGCTGGACTTTGAATGGACACTGAAGGCA
GGGGCTCTGGAGATGGCCCTCAAACGTGTTTACACCCTCCTGAGCTCCTGGAACTGCCTA
GAAGACTTTGATCAGATCTTCTGGGGCCAGAAGAGTGCCCTGGCTGAGAAGGTTCGCCAG
TGCTGGCAGGATGATGAGTTGTTCAGCTACCAGTTCCTCAATGGTGCCAACCCCATGCTG
TTGAGACGCTCGACCTCTCTGCCCTCCAGGCTAGTGCTGCCCTCGGGGATGGAAGAGCTT
CAGGCTCAACTGGAGAAAGAACTTCAGAATGGTTCCCTGTTTGAAGCTGACTTCATCCTT
CTGGATGGAATTCCAGCCAACGTGATCCGAGGAGAGAAGCAATACCTGGCTGCCCCCCTC
GTTATGCTGAAGATGGAGCCCAATGGGAAGCTGCAGCCCATGGTCATCCAGATTCAGCCT
CCCAACCCCAGCTCTCCAACCCCAACACTGTTCCTGCCCTCAGACCCCCCACTTGCCTGG
CTCCTGGCAAAGTCCTGGGTCCGAAATTCAGATTTCCAACTGCACGAGATCCAGTATCAC
TTGCTGAACACTCACCTGGTGGCTGAGGTCATCGCTGTCGCCACCATGCGGTGCCTCCCA
GGACTGCACCCCATCTTCAAGTTCCTGATCCCCCATATCCGCTACACCATGGAAATCAAC
ACCCGGGCCCGGACCCAACTCATCTCAGATGGAGGAATTTTTGATAAGGCAGTGAGCACA
GGTGGAGGGGGCCATGTACAGTTGCTCCGTCGGGCGGCAGCTCAGCTGACCTACTGCTCC
CTCTGTCCTCCTGACGACCTGGCTGACCGGGGCCTGCTGGGACTCCCAGGTGCTCTCTAT
GCCCATGATGCTTTACGGCTCTGGGAGATCATTGCCAGGTATGTGGAGGGGATCGTCCAC
CTCTTCTACCAAAGGGATGACATAGTGAAGGGGGACCCTGAGCTGCAGGCCTGGTGTCGG
GAGATCACGGAGGTGGGGCTGTGCCAGGCCCAGGACCGAGGTTTCCCTGTCTCCTTCCAG
TCCCAGAGTCAACTCTGCCATTTCCTCACCATGTGCGTCTTCACGTGCACTGCCCAGCAT
GCCGCCATCAACCAGGGCCAGCTGGACTGGTATGCCTGGGTCCCTAATGCTCCATGCACA
ATGCGGATGCCCCCACCCACCACCAAGGAAGATGTGACGATGGCCACAGTGATGGGGTCA
CTACCTGATGTCCGGCAGGCCTGTCTTCAAATGGCCATCTCATGGCATCTGAGTCGCCGC
CAGCCAGACATGGTGCCTCTGGGGCACCACAAAGAAAAATATTTCTCAGGCCCCAAGCCC
AAAGCTGTGCTAAACCAATTCCGAACAGATTTGGAAAAGCTGGAAAAGGAGATTACAGCC
CGGAATGAGCAACTTGACTGGCCCTATGAATATCTGAAGCCCAGCTGCATAGAGAACAGT
GTCACCATCTGA
GenBank Gene IDM35418
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:429
Chromosome Location17
Locus17p13.1
References
  1. Yoshimoto T, Yamamoto Y, Arakawa T, Suzuki H, Yamamoto S, Yokoyama C, Tanabe T, Toh H: Molecular cloning and expression of human arachidonate 12-lipoxygenase. Biochem Biophys Res Commun. 1990 Nov 15;172(3):1230-5. 2244907
  2. Funk CD, Furci L, FitzGerald GA: Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5638-42. 2377602
  3. Izumi T, Hoshiko S, Radmark O, Samuelsson B: Cloning of the cDNA for human 12-lipoxygenase. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7477-81. 2217179
  4. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. 16625196
  5. 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. 15489334
  6. Yoshimoto T, Arakawa T, Hada T, Yamamoto S, Takahashi E: Structure and chromosomal localization of human arachidonate 12-lipoxygenase gene. J Biol Chem. 1992 Dec 5;267(34):24805-9. 1447217
  7. Funk CD, Funk LB, FitzGerald GA, Samuelsson B: Characterization of human 12-lipoxygenase genes. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3962-6. 1570320
  8. Hussain H, Shornick LP, Shannon VR, Wilson JD, Funk CD, Pentland AP, Holtzman MJ: Epidermis contains platelet-type 12-lipoxygenase that is overexpressed in germinal layer keratinocytes in psoriasis. Am J Physiol. 1994 Jan;266(1 Pt 1):C243-53. 8304420
  9. Hada T, Ueda N, Takahashi Y, Yamamoto S: Catalytic properties of human platelet 12-lipoxygenase as compared with the enzymes of other origins. Biochim Biophys Acta. 1991 Apr 24;1083(1):89-93. 1851637
  10. Romano M, Chen XS, Takahashi Y, Yamamoto S, Funk CD, Serhan CN: Lipoxin synthase activity of human platelet 12-lipoxygenase. Biochem J. 1993 Nov 15;296 ( Pt 1):127-33. 8250832
  11. Chen XS, Brash AR, Funk CD: Purification and characterization of recombinant histidine-tagged human platelet 12-lipoxygenase expressed in a baculovirus/insect cell system. Eur J Biochem. 1993 Jun 15;214(3):845-52. 8319693
  12. Chen XS, Funk CD: Structure-function properties of human platelet 12-lipoxygenase: chimeric enzyme and in vitro mutagenesis studies. FASEB J. 1993 May;7(8):694-701. 8500694
  13. Hagmann W, Gao X, Timar J, Chen YQ, Strohmaier AR, Fahrenkopf C, Kagawa D, Lee M, Zacharek A, Honn KV: 12-Lipoxygenase in A431 cells: genetic identity, modulation of expression, and intracellular localization. Exp Cell Res. 1996 Nov 1;228(2):197-205. 8912711
  14. Nie D, Hillman GG, Geddes T, Tang K, Pierson C, Grignon DJ, Honn KV: Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates angiogenesis and tumor growth. Cancer Res. 1998 Sep 15;58(18):4047-51. 9751607
  15. Nie D, Krishnamoorthy S, Jin R, Tang K, Chen Y, Qiao Y, Zacharek A, Guo Y, Milanini J, Pages G, Honn KV: Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer cells. J Biol Chem. 2006 Jul 7;281(27):18601-9. Epub 2006 Apr 25. 16638750
  16. Yoo H, Jeon B, Jeon MS, Lee H, Kim TY: Reciprocal regulation of 12- and 15-lipoxygenases by UV-irradiation in human keratinocytes. FEBS Lett. 2008 Sep 22;582(21-22):3249-53. doi: 10.1016/j.febslet.2008.08.017. Epub 2008 Aug 26. 18755188
  17. Klampfl T, Bogner E, Bednar W, Mager L, Massudom D, Kalny I, Heinzle C, Berger W, Stattner S, Karner J, Klimpfinger M, Furstenberger G, Krieg P, Marian B: Up-regulation of 12(S)-lipoxygenase induces a migratory phenotype in colorectal cancer cells. Exp Cell Res. 2012 Apr 1;318(6):768-78. doi: 10.1016/j.yexcr.2011.12.017. Epub 2011 Dec 29. 22237009
  18. Weisinger G, Grafi-Cohen M, Hirsh M, Knoll E, Sharon O, Many A, Limor R, Stern N: 12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival. Exp Cell Res. 2013 Jun 10;319(10):1586-93. doi: 10.1016/j.yexcr.2013.04.001. Epub 2013 Apr 8. 23578768
  19. 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. 15308583
  20. Tan W, Wu J, Zhang X, Guo Y, Liu J, Sun T, Zhang B, Zhao D, Yang M, Yu D, Lin D: Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer. Carcinogenesis. 2007 Jun;28(6):1197-201. Epub 2006 Dec 6. 17151091
  21. Guo Y, Zhang X, Tan W, Miao X, Sun T, Zhao D, Lin D: Platelet 12-lipoxygenase Arg261Gln polymorphism: functional characterization and association with risk of esophageal squamous cell carcinoma in combination with COX-2 polymorphisms. Pharmacogenet Genomics. 2007 Mar;17(3):197-205. 17460548