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Identification
HMDB Protein ID HMDBP00972
Secondary Accession Numbers
  • 6260
  • HMDBP07113
Name Arachidonate 5-lipoxygenase
Synonyms
  1. 5-LO
  2. 5-lipoxygenase
Gene Name ALOX5
Protein Type Unknown
Biological Properties
General Function Involved in metal ion binding
Specific Function Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Pathways
  • Acetaminophen Action Pathway
  • Acetylsalicylic Acid Action Pathway
  • Antipyrine Action Pathway
  • Antrafenine Action Pathway
  • Arachidonic acid metabolism
  • Arachidonic Acid Metabolism
  • Bromfenac Action Pathway
  • Carprofen Action Pathway
  • Celecoxib Action Pathway
  • Diclofenac Action Pathway
  • Diflunisal Action Pathway
  • Etodolac Action Pathway
  • Etoricoxib Action Pathway
  • Fenoprofen Action Pathway
  • Flurbiprofen Action Pathway
  • Ibuprofen Action Pathway
  • Indomethacin Action Pathway
  • Ketoprofen Action Pathway
  • Ketorolac Action Pathway
  • leukotriene A4 biosynthesis
  • Leukotriene C4 Synthesis Deficiency
  • Lornoxicam Action Pathway
  • Lumiracoxib Action Pathway
  • Magnesium salicylate Action Pathway
  • Mefenamic Acid Action Pathway
  • Meloxicam Action Pathway
  • Nabumetone Action Pathway
  • Naproxen Action Pathway
  • Nepafenac Action Pathway
  • Oxaprozin Action Pathway
  • Phenylbutazone Action Pathway
  • Piroxicam Action Pathway
  • Rofecoxib Action Pathway
  • Salicylate-sodium Action Pathway
  • Salicylic Acid Action Pathway
  • Salsalate Action Pathway
  • Serotonergic synapse
  • Sulindac Action Pathway
  • Suprofen Action Pathway
  • Tenoxicam Action Pathway
  • Tiaprofenic Acid Action Pathway
  • Tolmetin Action Pathway
  • Toxoplasmosis
  • Trisalicylate-choline Action Pathway
  • Valdecoxib Action Pathway
Reactions
Arachidonic acid + Oxygen → leukotriene A(4) + Water details
Arachidonic acid + Oxygen → 5(S)-Hydroperoxyeicosatetraenoic acid details
5(S)-Hydroperoxyeicosatetraenoic acid → Leukotriene A4 + Water details
Arachidonic acid + Oxygen → Leukotriene A4 + Water details
GO Classification
Biological Process
positive regulation of vasoconstriction
acute inflammatory response
response to nutrient
leukotriene production involved in inflammatory response
lipoxygenase pathway
sensory perception of pain
arachidonic acid metabolic process
leukotriene biosynthetic process
response to hyperoxia
Cellular Component
cytosol
dendrite
nuclear matrix
nuclear membrane
nuclear envelope lumen
sarcolemma
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
transition metal ion binding
iron ion binding
lipoxygenase activity
oxidoreductase activity
Molecular Function
lipoxygenase activity
arachidonate 5-lipoxygenase activity
iron ion binding
Process
metabolic process
cellular metabolic process
organic acid metabolic process
oxoacid metabolic process
carboxylic acid metabolic process
monocarboxylic acid metabolic process
fatty acid metabolic process
oxidation reduction
unsaturated fatty acid metabolic process
icosanoid metabolic process
leukotriene metabolic process
Cellular Location
  1. Cytoplasm
  2. Peripheral membrane protein
  3. Nucleus matrix
  4. Nucleus membrane
Gene Properties
Chromosome Location 10
Locus 10q11.2
SNPs ALOX5
Gene Sequence
>2025 bp
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
Protein Properties
Number of Residues 674
Molecular Weight 77982.595
Theoretical pI 5.775
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Arachidonate 5-lipoxygenase
MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDE
ELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLA
RDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVL
NYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNG
CNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDP
CTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDF
HVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECG
LFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWE
AIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYL
TVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCW
HLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPY
YYLSPDRIPNSVAI
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P09917
UniProtKB/Swiss-Prot Entry Name LOX5_HUMAN
PDB IDs
GenBank Gene ID J03600
GeneCard ID ALOX5
GenAtlas ID ALOX5
HGNC ID HGNC:435
References
General References
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  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  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. 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 ]
  17. 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 ]