ID LOX5_HUMAN Reviewed; 674 AA. AC P09917; B7ZLS0; E5FPY5; E5FPY7; E5FPY8; Q5JQ14; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 27-MAR-2024, entry version 229. DE RecName: Full=Polyunsaturated fatty acid 5-lipoxygenase {ECO:0000305}; DE EC=1.13.11.- {ECO:0000269|PubMed:31664810}; DE AltName: Full=Arachidonate 5-lipoxygenase; DE Short=5-LO {ECO:0000303|PubMed:3422434}; DE Short=5-lipoxygenase {ECO:0000303|PubMed:3422434}; DE EC=1.13.11.34 {ECO:0000269|PubMed:21233389}; GN Name=ALOX5 {ECO:0000312|HGNC:HGNC:435}; Synonyms=LOG5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3422434; DOI=10.1073/pnas.85.2.416; RA Dixon R.A.F., Jones R.E., Diehl R.E., Bennett C.D., Kargman S., RA Rouzer C.A.; RT "Cloning of the cDNA for human 5-lipoxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 85:416-420(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2829172; DOI=10.1073/pnas.85.1.26; RA Matsumoto T., Funk C.D., Raadmark O., Hoeoeg J.-O., Joernvall H., RA Samuelsson B.; RT "Molecular cloning and amino acid sequence of human 5-lipoxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 85:26-30(1988). RN [3] RP ERRATUM OF PUBMED:2829172. RA Matsumoto T., Funk C.D., Raadmark O., Hoeoeg J.-O., Joernvall H., RA Samuelsson B.; RL Proc. Natl. Acad. Sci. U.S.A. 85:3406-3406(1988). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=2526519; RA Matsumoto T., Funk C.D., Raadmark O., Hoeoeg J.-O., Joernvall H., RA Samuelsson B.; RT "Molecular cloning and amino acid sequence of human 5-lipoxygenase."; RL Adv. Prostaglandin Thromboxane Leukotriene Res. 19:466-469(1989). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5). RX PubMed=21098726; DOI=10.1096/fj.10-173856; RA Boudreau L.H., Bertin J., Robichaud P.P., Laflamme M., Ouellette R.J., RA Flamand N., Surette M.E.; RT "Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase RT products."; RL FASEB J. 25:1097-1105(2011). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50. RX PubMed=2565035; DOI=10.1073/pnas.86.8.2587; RA Funk C.D., Hoshiko S., Matsumoto T., Raadmark O., Samuelsson B.; RT "Characterization of the human 5-lipoxygenase gene."; RL Proc. Natl. Acad. Sci. U.S.A. 86:2587-2591(1989). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11. RX PubMed=2251250; DOI=10.1073/pnas.87.23.9073; RA Hoshiko S., Raadmark O., Samuelsson B.; RT "Characterization of the human 5-lipoxygenase gene promoter."; RL Proc. Natl. Acad. Sci. U.S.A. 87:9073-9077(1990). RN [10] RP SUBCELLULAR LOCATION. RX PubMed=3118366; DOI=10.1073/pnas.84.21.7393; RA Rouzer C.A., Samuelsson B.; RT "Reversible, calcium-dependent membrane association of human leukocyte 5- RT lipoxygenase."; RL Proc. Natl. Acad. Sci. U.S.A. 84:7393-7397(1987). RN [11] RP MUTAGENESIS OF HIS-363; HIS-368; HIS-373; HIS-391 AND HIS-400. RX PubMed=1939225; DOI=10.1016/s0021-9258(18)54744-x; RA Nguyen T., Falgueyret J.-P., Abramowitz M., Riendeau D.; RT "Evaluation of the role of conserved His and Met residues among RT lipoxygenases by site-directed mutagenesis of recombinant human 5- RT lipoxygenase."; RL J. Biol. Chem. 266:22057-22062(1991). RN [12] RP MUTAGENESIS OF HIS-368; HIS-373; GLU-377; HIS-391; HIS-400 AND HIS-551. RX PubMed=1540191; DOI=10.1016/0006-291x(92)91901-2; RA Ishii S., Noguchi M., Miyano M., Matsumoto T., Noma M.; RT "Mutagenesis studies on the amino acid residues involved in the iron- RT binding and the activity of human 5-lipoxygenase."; RL Biochem. Biophys. Res. Commun. 182:1482-1490(1992). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=8245774; DOI=10.1084/jem.178.6.1935; RA Woods J.W., Evans J.F., Ethier D., Scott S., Vickers P.J., Hearn L., RA Heibein J.A., Charleson S., Singer I.I.; RT "5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the RT nuclear envelope of activated human leukocytes."; RL J. Exp. Med. 178:1935-1946(1993). RN [14] RP INTERACTION WITH GRB2. RX PubMed=7929073; DOI=10.1016/s0021-9258(19)51063-8; RA Lepley R.A., Fitzpatrick F.A.; RT "5-Lipoxygenase contains a functional Src homology 3-binding motif that RT interacts with the Src homology 3 domain of Grb2 and cytoskeletal RT proteins."; RL J. Biol. Chem. 269:24163-24168(1994). RN [15] RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=8615788; DOI=10.1042/bj3140911; RA Petrich K., Ludwig P., Kuehn H., Schewe T.; RT "The suppression of 5-lipoxygenation of arachidonic acid in human RT polymorphonuclear leucocytes by the 15-lipoxygenase product (15S)-hydroxy- RT (5Z,8Z,11Z,13E)-eicosatetraenoic acid: structure-activity relationship and RT mechanism of action."; RL Biochem. J. 314:911-916(1996). RN [16] RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=8631361; DOI=10.1111/j.1432-1033.1996.00416.x; RA De Carolis E., Denis D., Riendeau D.; RT "Oxidative inactivation of human 5-lipoxygenase in phosphatidylcholine RT vesicles."; RL Eur. J. Biochem. 235:416-423(1996). RN [17] RP PHOSPHORYLATION AT SER-272. RX PubMed=11844797; DOI=10.1074/jbc.m111945200; RA Werz O., Szellas D., Steinhilber D., Radmark O.; RT "Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by RT MAPK-activated protein kinase 2 (MK2)."; RL J. Biol. Chem. 277:14793-14800(2002). RN [18] RP PHOSPHORYLATION AT SER-524, AND MUTAGENESIS OF SER-524. RX PubMed=15280375; DOI=10.1074/jbc.m312568200; RA Luo M., Jones S.M., Phare S.M., Coffey M.J., Peters-Golden M., Brock T.G.; RT "Protein kinase A inhibits leukotriene synthesis by phosphorylation of 5- RT lipoxygenase on serine 523."; RL J. Biol. Chem. 279:41512-41520(2004). RN [19] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=17114001; DOI=10.1016/j.chembiol.2006.09.011; RA Tjonahen E., Oh S.F., Siegelman J., Elangovan S., Percarpio K.B., Hong S., RA Arita M., Serhan C.N.; RT "Resolvin E2: identification and anti-inflammatory actions: pivotal role of RT human 5-lipoxygenase in resolvin E series biosynthesis."; RL Chem. Biol. 13:1193-1202(2006). RN [20] RP SUBCELLULAR LOCATION. RX PubMed=16275640; DOI=10.1074/jbc.m506513200; RA Flamand N., Lefebvre J., Surette M.E., Picard S., Borgeat P.; RT "Arachidonic acid regulates the translocation of 5-lipoxygenase to the RT nuclear membranes in human neutrophils."; RL J. Biol. Chem. 281:129-136(2006). RN [21] RP INTERACTION WITH DICER1, SUBCELLULAR LOCATION, MUTAGENESIS OF TRP-14; RP TRP-76 AND TRP-103, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=19022417; DOI=10.1016/j.bbagrm.2008.10.002; RA Dincbas-Renqvist V., Pepin G., Rakonjac M., Plante I., Ouellet D.L., RA Hermansson A., Goulet I., Doucet J., Samuelsson B., Raadmark O., RA Provost P.; RT "Human Dicer C-terminus functions as a 5-lipoxygenase binding domain."; RL Biochim. Biophys. Acta 1789:99-108(2009). RN [22] RP INTERACTION WITH ALOX5AP AND LTC4S, AND SUBCELLULAR LOCATION. RX PubMed=19233132; DOI=10.1016/j.bbrc.2009.02.074; RA Strid T., Svartz J., Franck N., Hallin E., Ingelsson B., Soederstroem M., RA Hammarstroem S.; RT "Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase RT and 5-lipoxygenase activating protein."; RL Biochem. Biophys. Res. Commun. 381:518-522(2009). RN [23] RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-272, AND MUTAGENESIS OF RP SER-272. RX PubMed=18978352; DOI=10.1074/jbc.m805593200; RA Flamand N., Luo M., Peters-Golden M., Brock T.G.; RT "Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear RT export."; RL J. Biol. Chem. 284:306-313(2009). RN [24] RP INTERACTION WITH COTL1, AND MUTAGENESIS OF TRP-103. RX PubMed=19807693; DOI=10.1042/bj20090856; RA Esser J., Rakonjac M., Hofmann B., Fischer L., Provost P., Schneider G., RA Steinhilber D., Samuelsson B., Radmark O.; RT "Coactosin-like protein functions as a stabilizing chaperone for 5- RT lipoxygenase: role of tryptophan 102."; RL Biochem. J. 425:265-274(2010). RN [25] RP INTERACTION WITH PIK3R1, AND FUNCTION. RX PubMed=21200133; DOI=10.3858/emm.2011.43.2.012; RA Ha Y.J., Seul H.J., Lee J.R.; RT "Ligation of CD40 receptor in human B lymphocytes triggers the 5- RT lipoxygenase pathway to produce reactive oxygen species and activate p38 RT MAPK."; RL Exp. Mol. Med. 43:101-110(2011). RN [26] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=21206090; DOI=10.1172/jci42545; RA Oh S.F., Pillai P.S., Recchiuti A., Yang R., Serhan C.N.; RT "Pro-resolving actions and stereoselective biosynthesis of 18S E-series RT resolvins in human leukocytes and murine inflammation."; RL J. Clin. Invest. 121:569-581(2011). RN [27] RP CATALYTIC ACTIVITY, FUNCTION, AND MUTAGENESIS OF PHE-360; ALA-425; ASN-426 RP AND ALA-604. RX PubMed=23246375; DOI=10.1016/j.abb.2012.11.015; RA Hofheinz K., Kakularam K.R., Adel S., Anton M., Polymarasetty A., RA Reddanna P., Kuhn H., Horn T.; RT "Conversion of pro-inflammatory murine Alox5 into an anti-inflammatory 15S- RT lipoxygenating enzyme by multiple mutations of sequence determinants."; RL Arch. Biochem. Biophys. 530:40-47(2013). RN [28] RP CATALYTIC ACTIVITY, FUNCTION, VARIANTS LYS-254; SER-337; SER-447; VAL-549; RP LEU-577; MET-591 AND GLN-656, AND CHARACTERIZATION OF VARIANTS LYS-254; RP SER-337; SER-447; VAL-549; LEU-577; MET-591 AND GLN-656. RX PubMed=24282679; DOI=10.1016/j.redox.2013.11.001; RA Horn T., Reddy Kakularam K., Anton M., Richter C., Reddanna P., Kuhn H.; RT "Functional characterization of genetic enzyme variations in human RT lipoxygenases."; RL Redox Biol. 1:566-577(2013). RN [29] RP CATALYTIC ACTIVITY, FUNCTION, INDUCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=24893149; DOI=10.1021/bi401621d; RA Smyrniotis C.J., Barbour S.R., Xia Z., Hixon M.S., Holman T.R.; RT "ATP allosterically activates the human 5-lipoxygenase molecular mechanism RT of arachidonic acid and 5(S)-hydroperoxy-6(E),8(Z),11(Z),14(Z)- RT eicosatetraenoic acid."; RL Biochemistry 53:4407-4419(2014). RN [30] RP PHOSPHORYLATION AT SER-524. RX PubMed=26210919; DOI=10.1016/j.plefa.2015.06.003; RA Mahshid Y., Markoutsa S., Dincbas-Renqvist V., Sueruen D., Christensson B., RA Sander B., Bjoerkholm M., Sorg B.L., Raadmark O., Claesson H.E.; RT "Phosphorylation of serine 523 on 5-lipoxygenase in human B lymphocytes."; RL Prostaglandins Leukot. Essent. Fatty Acids 100:33-40(2015). RN [31] RP MUTAGENESIS OF PHE-360; ALA-425; ASN-426 AND ALA-604, CATALYTIC ACTIVITY, RP AND FUNCTION. RX PubMed=31664810; DOI=10.1021/acschembio.9b00674; RA Ivanov I., Golovanov A.B., Ferretti C., Canyelles-Nino M., Heydeck D., RA Stehling S., Lluch J.M., Gonzalez-Lafont A., Kuehn H.; RT "Mutations of Triad Determinants Changes the Substrate Alignment at the RT Catalytic Center of Human ALOX5."; RL ACS Chem. Biol. 14:2768-2782(2019). RN [32] {ECO:0007744|PDB:3O8Y} RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH IRON ION, COFACTOR, RP CATALYTIC ACTIVITY, FUNCTION, AND SUBUNIT. RX PubMed=21233389; DOI=10.1126/science.1197203; RA Gilbert N.C., Bartlett S.G., Waight M.T., Neau D.B., Boeglin W.E., RA Brash A.R., Newcomer M.E.; RT "The structure of human 5-lipoxygenase."; RL Science 331:217-219(2011). RN [33] {ECO:0007744|PDB:3V92, ECO:0007744|PDB:3V98, ECO:0007744|PDB:3V99} RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) IN COMPLEX WITH IRON ION AND RP ARACHIDONIC ACID, SUBUNIT, MUTAGENESIS OF SER-664, BIOPHYSICOCHEMICAL RP PROPERTIES, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=22516296; DOI=10.1096/fj.12-205286; RA Gilbert N.C., Rui Z., Neau D.B., Waight M.T., Bartlett S.G., Boeglin W.E., RA Brash A.R., Newcomer M.E.; RT "Conversion of human 5-lipoxygenase to a 15-lipoxygenase by a point RT mutation to mimic phosphorylation at Serine-663."; RL FASEB J. 26:3222-3229(2012). RN [34] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32404334; DOI=10.1194/jlr.ra120000777; RA Perry S.C., Kalyanaraman C., Tourdot B.E., Conrad W.S., Akinkugbe O., RA Freedman J.C., Holinstat M., Jacobson M.P., Holman T.R.; RT "15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15- RT lipoxygenase-2 in biosynthesis of resolvin D5."; RL J. Lipid Res. 61:1087-1103(2020). RN [35] RP VARIANT LYS-254. RX PubMed=15308583; DOI=10.1093/carcin/bgh260; RA Goodman J.E., Bowman E.D., Chanock S.J., Alberg A.J., Harris C.C.; RT "Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms RT and colon cancer risk."; RL Carcinogenesis 25:2467-2472(2004). CC -!- FUNCTION: Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)- CC eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed CC by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene CC A4/LTA4), the first two steps in the biosynthesis of leukotrienes, CC which are potent mediators of inflammation (PubMed:8631361, CC PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, CC PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). CC Also catalyzes the oxygenation of arachidonate into 8- CC hydroperoxyicosatetraenoate (8-HPETE) and 12- CC hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays CC lipoxin synthase activity being able to convert (15S)-HETE into a CC conjugate tetraene (PubMed:31664810). Although arachidonate is the CC preferred substrate, this enzyme can also metabolize oxidized fatty CC acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate CC (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which CC lead to the formation of specialized pro-resolving mediators (SPM) CC lipoxin and resolvins E and D respectively, therefore it participates CC in anti-inflammatory responses (PubMed:21206090, PubMed:31664810, CC PubMed:8615788, PubMed:17114001, PubMed:32404334). Oxidation of DHA CC directly inhibits endothelial cell proliferation and sprouting CC angiogenesis via peroxisome proliferator-activated receptor gamma CC (PPARgamma) (By similarity). It does not catalyze the oxygenation of CC linoleic acid and does not convert (5S)-HETE to lipoxin isomers CC (PubMed:31664810). In addition to inflammatory processes, it CC participates in dendritic cell migration, wound healing through an CC antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation CC expression, monocyte adhesion to the endothelium via ITGAM expression CC on monocytes (By similarity). Moreover, it helps establish an adaptive CC humoral immunity by regulating primary resting B cells and follicular CC helper T cells and participates in the CD40-induced production of CC reactive oxygen species (ROS) after CD40 ligation in B cells through CC interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). CC May also play a role in glucose homeostasis, regulation of insulin CC secretion and palmitic acid-induced insulin resistance via AMPK (By CC similarity). Can regulate bone mineralization and fat cell CC differentiation increases in induced pluripotent stem cells (By CC similarity). {ECO:0000250|UniProtKB:P48999, CC ECO:0000269|PubMed:17114001, ECO:0000269|PubMed:19022417, CC ECO:0000269|PubMed:21200133, ECO:0000269|PubMed:21206090, CC ECO:0000269|PubMed:21233389, ECO:0000269|PubMed:22516296, CC ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:24282679, CC ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:31664810, CC ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8615788, CC ECO:0000269|PubMed:8631361}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = H2O + leukotriene A4; CC Xref=Rhea:RHEA:32307, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57463; EC=1.13.11.34; CC Evidence={ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:21233389}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32308; CC Evidence={ECO:0000269|PubMed:21233389}; CC -!- CATALYTIC ACTIVITY: CC Reaction=18-HEPE + O2 = (5S)-hydroperoxy-18-hydroxy- CC (7E,9E,11Z,14Z,16E)-eicosapentaenoate; Xref=Rhea:RHEA:48860, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:90825, ChEBI:CHEBI:90826; CC Evidence={ECO:0000269|PubMed:17114001}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48861; CC Evidence={ECO:0000305|PubMed:17114001}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = CC (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate; CC Xref=Rhea:RHEA:51968, ChEBI:CHEBI:15379, ChEBI:CHEBI:90818, CC ChEBI:CHEBI:132218; Evidence={ECO:0000269|PubMed:21206090}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51969; CC Evidence={ECO:0000305|PubMed:21206090}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = CC (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate; CC Xref=Rhea:RHEA:50204, ChEBI:CHEBI:15379, ChEBI:CHEBI:132083, CC ChEBI:CHEBI:132091; Evidence={ECO:0000269|PubMed:21206090}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50205; CC Evidence={ECO:0000305|PubMed:21206090}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)- CC eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate + H2O; Xref=Rhea:RHEA:39107, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:132091, ChEBI:CHEBI:134661; CC Evidence={ECO:0000269|PubMed:21206090}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39108; CC Evidence={ECO:0000305|PubMed:21206090}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)- CC eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate + H2O; Xref=Rhea:RHEA:50268, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:132218, ChEBI:CHEBI:132219; CC Evidence={ECO:0000269|PubMed:21206090, ECO:0000305|PubMed:17114001}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50269; CC Evidence={ECO:0000305|PubMed:21206090}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate = (5S,6S)-epoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate + H2O; Xref=Rhea:RHEA:50844, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:90826, ChEBI:CHEBI:133812; CC Evidence={ECO:0000269|PubMed:17114001}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50845; CC Evidence={ECO:0000305|PubMed:17114001}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy- CC (6E,8Z,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:17485, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57450; CC Evidence={ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:22516296, CC ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:24282679, CC ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:8615788, CC ECO:0000269|PubMed:8631361}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17486; CC Evidence={ECO:0000305|PubMed:8631361}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 = (5S)- CC hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate; CC Xref=Rhea:RHEA:48624, ChEBI:CHEBI:15379, ChEBI:CHEBI:57409, CC ChEBI:CHEBI:131564; Evidence={ECO:0000269|PubMed:31664810, CC ECO:0000269|PubMed:8615788}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48625; CC Evidence={ECO:0000269|PubMed:8615788}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = H2O + CC leukotriene A4; Xref=Rhea:RHEA:17961, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57450, ChEBI:CHEBI:57463; CC Evidence={ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24893149, CC ECO:0000269|PubMed:8631361}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17962; CC Evidence={ECO:0000305|PubMed:8631361}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy- CC (5Z,9E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:38675, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75322; CC Evidence={ECO:0000269|PubMed:23246375}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38676; CC Evidence={ECO:0000305|PubMed:23246375}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy- CC (5Z,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:10428, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57444; CC Evidence={ECO:0000269|PubMed:23246375}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429; CC Evidence={ECO:0000305|PubMed:23246375}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z)-eicosadienoate + O2 = (5S)-hydroperoxy-(6E,8Z)- CC eicosadienoate; Xref=Rhea:RHEA:62644, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:145835, ChEBI:CHEBI:145836; CC Evidence={ECO:0000305|PubMed:8631361}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 = (5S)- CC hydroperoxy-(12S)-hydroxy-(6E,8Z,10E,14Z)-eicosatetraenoate; CC Xref=Rhea:RHEA:62648, ChEBI:CHEBI:15379, ChEBI:CHEBI:90680, CC ChEBI:CHEBI:145837; Evidence={ECO:0000305|PubMed:8631361}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 5-hydroperoxy- CC (6E,8Z,11Z,14Z,17Z)-eicosapentaenoate; Xref=Rhea:RHEA:62600, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:58562, ChEBI:CHEBI:145815; CC Evidence={ECO:0000269|PubMed:31664810}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62601; CC Evidence={ECO:0000305|PubMed:31664810}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)- CC hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:41332, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:78048; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (7S)- CC hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:64668, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:156049; Evidence={ECO:0000269|PubMed:32404334, CC ECO:0000305|PubMed:31664810}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64669; CC Evidence={ECO:0000305|PubMed:31664810, ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)- CC hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:50840, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:133795; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50841; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00726, ECO:0000269|PubMed:21233389}; CC Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE- CC ProRule:PRU00726, ECO:0000269|PubMed:21233389}; CC -!- ACTIVITY REGULATION: Undergoes a sequential loss of the oxygenase and CC pseudoperoxidase activities which is dependent on the structural CC characteristics of the substrate for the reaction, on oxygen CC concentration and on exposure to phospholipids and calcium CC (PubMed:8631361). 15-HETE and other 15-mono-hydroxyeicosanoids exhibit CC the highest inhibitory potencies in their capability of suppressing 5- CC lipoxygenation of arachidonic acid, whereas the other HETEs, (5S,15S)- CC dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5,15-diHETE) as well CC as octadecanoids, are modest or poor inhibitors (PubMed:8615788). The CC formation of (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)- CC eicosatetraenoate is strongly stimulated by either hydroperoxypolyenoic CC fatty acids or arachidonic acid (PubMed:8615788). Arachidonate 5- CC lipoxygenase and leukotriene A4 synthase activities are allosterically CC increased by ATP (PubMed:24893149). {ECO:0000269|PubMed:24893149, CC ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=13 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate CC {ECO:0000269|PubMed:8631361}; CC KM=11 uM for arachidonic acid {ECO:0000269|PubMed:22516296}; CC KM=1.9 uM for arachidonic acid {ECO:0000269|PubMed:24893149}; CC KM=14 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate CC {ECO:0000269|PubMed:24893149}; CC KM=5.3 uM for arachidonic acid (in the presence of 200 uM ATP) CC {ECO:0000269|PubMed:24893149}; CC KM=19 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (in CC the presence of 200 uM ATP) {ECO:0000269|PubMed:24893149}; CC KM=1.6 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate CC (generated in situ from arachidonic acid) CC {ECO:0000269|PubMed:24893149}; CC KM=4.5 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate CC (generated in situ from arachidonic acid in the presence of 200 uM CC ATP) {ECO:0000269|PubMed:24893149}; CC Vmax=1 umol/min/mg enzyme toward arachidonic acid CC {ECO:0000269|PubMed:24893149}; CC Vmax=0.33 umol/min/mg enzyme toward CC (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate CC {ECO:0000269|PubMed:24893149}; CC Vmax=4.9 umol/min/mg enzyme toward arachidonic acid (in the presence CC of 200 uM ATP) {ECO:0000269|PubMed:24893149}; CC Vmax=1.6 umol/min/mg enzyme toward CC (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (in the presence CC of 200 uM ATP) {ECO:0000269|PubMed:24893149}; CC Vmax=0.1 umol/min/mg enzyme toward CC (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (generated in situ CC from arachidonic acid) {ECO:0000269|PubMed:24893149}; CC Vmax=2 umol/min/mg enzyme toward CC (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (generated in situ CC from arachidonic acid in the presence of 200 uM ATP) CC {ECO:0000269|PubMed:24893149}; CC -!- PATHWAY: Lipid metabolism; leukotriene A4 biosynthesis. CC {ECO:0000269|PubMed:8631361}. CC -!- SUBUNIT: Homodimer (PubMed:22516296, PubMed:21233389). Interacts with CC ALOX5AP and LTC4S (PubMed:19233132). Interacts with COTL1, the CC interaction is required for stability and efficient catalytic activity CC (PubMed:19807693). Interacts with PIK3R1; this interaction bridges CC ALOX5 with CD40 after CD40 ligation in B cells and leads to the CC production of reactive oxygen species (ROS) (PubMed:21200133). CC Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold CC domain); this interaction enhances arachidonate 5-lipoxygenase activity CC and modifies the miRNA precursor processing activity of DICER1 CC (PubMed:19022417). {ECO:0000269|PubMed:19022417, CC ECO:0000269|PubMed:19233132, ECO:0000269|PubMed:19807693, CC ECO:0000269|PubMed:21200133, ECO:0000269|PubMed:21233389, CC ECO:0000269|PubMed:22516296}. CC -!- INTERACTION: CC P09917; Q8IYJ2-2: C10orf67; NbExp=3; IntAct=EBI-79934, EBI-13381098; CC P09917; Q6PII3: CCDC174; NbExp=3; IntAct=EBI-79934, EBI-747830; CC P09917; Q6P2R3: CEP57L1; NbExp=3; IntAct=EBI-79934, EBI-12696312; CC P09917; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-79934, EBI-10181988; CC P09917; Q96MT8: CEP63; NbExp=4; IntAct=EBI-79934, EBI-741977; CC P09917; Q96MT8-3: CEP63; NbExp=8; IntAct=EBI-79934, EBI-11522539; CC P09917; Q14019: COTL1; NbExp=5; IntAct=EBI-79934, EBI-79926; CC P09917; P09769: FGR; NbExp=2; IntAct=EBI-79934, EBI-1383732; CC P09917; O43716: GATC; NbExp=6; IntAct=EBI-79934, EBI-6929453; CC P09917; P08631: HCK; NbExp=2; IntAct=EBI-79934, EBI-346340; CC P09917; Q6UWX4: HHIPL2; NbExp=6; IntAct=EBI-79934, EBI-10196655; CC P09917; P14061: HSD17B1; NbExp=3; IntAct=EBI-79934, EBI-12867244; CC P09917; P31025: LCN1; NbExp=3; IntAct=EBI-79934, EBI-1052433; CC P09917; Q9Y6D9: MAD1L1; NbExp=9; IntAct=EBI-79934, EBI-742610; CC P09917; P50221: MEOX1; NbExp=3; IntAct=EBI-79934, EBI-2864512; CC P09917; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-79934, EBI-16439278; CC P09917; Q86Y26: NUTM1; NbExp=4; IntAct=EBI-79934, EBI-10178410; CC P09917; A6NGQ2: OOEP; NbExp=3; IntAct=EBI-79934, EBI-18583589; CC P09917; P17612: PRKACA; NbExp=2; IntAct=EBI-79934, EBI-476586; CC P09917; Q04864: REL; NbExp=3; IntAct=EBI-79934, EBI-307352; CC P09917; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-79934, EBI-5235340; CC P09917; Q8N0S2: SYCE1; NbExp=6; IntAct=EBI-79934, EBI-6872807; CC P09917; Q9P0N9: TBC1D7; NbExp=3; IntAct=EBI-79934, EBI-3258000; CC P09917; P07947: YES1; NbExp=2; IntAct=EBI-79934, EBI-515331; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P48999, CC ECO:0000269|PubMed:18978352}. Nucleus matrix CC {ECO:0000269|PubMed:19233132}. Nucleus membrane CC {ECO:0000269|PubMed:16275640}; Peripheral membrane protein CC {ECO:0000269|PubMed:16275640}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:19022417}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:19233132}. Nucleus envelope CC {ECO:0000269|PubMed:16275640, ECO:0000269|PubMed:19233132, CC ECO:0000269|PubMed:8245774}. Nucleus intermembrane space CC {ECO:0000269|PubMed:8245774}. Note=Shuttles between cytoplasm and CC nucleus (PubMed:19233132). Found exclusively in the nucleus, when CC phosphorylated on Ser-272 (PubMed:18978352). Calcium binding promotes CC translocation from the cytosol and the nuclear matrix to the nuclear CC envelope and membrane association (PubMed:19233132, PubMed:3118366, CC PubMed:8245774, PubMed:16275640). {ECO:0000269|PubMed:16275640, CC ECO:0000269|PubMed:18978352, ECO:0000269|PubMed:19233132, CC ECO:0000269|PubMed:3118366, ECO:0000269|PubMed:8245774}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=P09917-1; Sequence=Displayed; CC Name=2; Synonyms=Delta-13; CC IsoId=P09917-2; Sequence=VSP_046998; CC Name=3; Synonyms=delta-p10; CC IsoId=P09917-3; Sequence=VSP_053534; CC Name=4; Synonyms=delta-10-13; CC IsoId=P09917-4; Sequence=VSP_053535, VSP_053537; CC Name=5; Synonyms=alpha-10; CC IsoId=P09917-5; Sequence=VSP_053536; CC -!- PTM: Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic CC acid (PubMed:11844797, PubMed:18978352). Phosphorylation on Ser-524 by CC PKA has an inhibitory effect (PubMed:15280375). Phosphorylation on Ser- CC 272 prevents export from the nucleus (PubMed:11844797, CC PubMed:18978352). Phosphorylation at Ser-524 is stimulated by 8-bromo- CC 3',5'-cyclic AMP or prostaglandin E2 (PubMed:26210919). CC {ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:15280375, CC ECO:0000269|PubMed:18978352, ECO:0000269|PubMed:26210919}. CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42985/ALOX5"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; J03600; AAA36183.1; -; mRNA. DR EMBL; J03571; AAA65450.1; -; mRNA. DR EMBL; HM592258; ADR30798.1; -; mRNA. DR EMBL; HM592259; ADR30799.1; -; mRNA. DR EMBL; HM592260; ADR30800.1; -; mRNA. DR EMBL; HM592261; ADR30801.1; -; mRNA. DR EMBL; J04520; AAA59522.1; -; Genomic_DNA. DR EMBL; AL731567; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC130332; AAI30333.1; -; mRNA. DR EMBL; BC132677; AAI32678.1; -; mRNA. DR EMBL; BC143985; AAI43986.1; -; mRNA. DR EMBL; M38191; AAA63212.1; -; Genomic_DNA. DR CCDS; CCDS58078.1; -. [P09917-2] DR CCDS; CCDS7212.1; -. [P09917-1] DR PIR; A28117; DAHUAL. DR RefSeq; NP_000689.1; NM_000698.4. [P09917-1] DR RefSeq; NP_001243082.1; NM_001256153.2. [P09917-3] DR RefSeq; NP_001243083.1; NM_001256154.2. [P09917-2] DR RefSeq; NP_001307790.1; NM_001320861.1. DR PDB; 3O8Y; X-ray; 2.39 A; A/B=1-674. DR PDB; 3V92; X-ray; 2.74 A; A/B=1-674. DR PDB; 3V98; X-ray; 2.07 A; A/B=1-674. DR PDB; 3V99; X-ray; 2.25 A; A/B=1-674. DR PDB; 6N2W; X-ray; 2.71 A; A/B=1-674. DR PDB; 6NCF; X-ray; 2.87 A; A/B/C/D=1-674. DR PDB; 7TTJ; X-ray; 2.10 A; A/B=1-674. DR PDB; 7TTK; X-ray; 1.98 A; A/B=1-674. DR PDB; 7TTL; X-ray; 2.43 A; A/B/C/D=1-674. DR PDBsum; 3O8Y; -. DR PDBsum; 3V92; -. DR PDBsum; 3V98; -. DR PDBsum; 3V99; -. DR PDBsum; 6N2W; -. DR PDBsum; 6NCF; -. DR PDBsum; 7TTJ; -. DR PDBsum; 7TTK; -. DR PDBsum; 7TTL; -. DR AlphaFoldDB; P09917; -. DR EMDB; EMD-40299; -. DR EMDB; EMD-40300; -. DR EMDB; EMD-40301; -. DR EMDB; EMD-40302; -. DR EMDB; EMD-40304; -. DR SMR; P09917; -. DR BioGRID; 106741; 105. DR DIP; DIP-30950N; -. DR IntAct; P09917; 65. DR MINT; P09917; -. DR STRING; 9606.ENSP00000363512; -. DR BindingDB; P09917; -. DR ChEMBL; CHEMBL215; -. DR DrugBank; DB14001; alpha-Tocopherol succinate. DR DrugBank; DB00233; Aminosalicylic acid. DR DrugBank; DB01014; Balsalazide. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB14002; D-alpha-Tocopherol acetate. DR DrugBank; DB11994; Diacerein. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB00711; Diethylcarbamazine. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB01892; Hyperforin. DR DrugBank; DB00159; Icosapent. DR DrugBank; DB04725; Licofelone. DR DrugBank; DB00179; Masoprocol. DR DrugBank; DB00939; Meclofenamic acid. DR DrugBank; DB14009; Medical Cannabis. DR DrugBank; DB00244; Mesalazine. DR DrugBank; DB01017; Minocycline. DR DrugBank; DB05431; MLN-977. DR DrugBank; DB00471; Montelukast. DR DrugBank; DB09285; Morniflumate. DR DrugBank; DB14011; Nabiximols. DR DrugBank; DB11133; Omega-3 fatty acids. DR DrugBank; DB13168; Omega-6 fatty acids. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB13174; Rhein. DR DrugBank; DB00795; Sulfasalazine. DR DrugBank; DB00163; Vitamin E. DR DrugBank; DB00744; Zileuton. DR DrugCentral; P09917; -. DR GuidetoPHARMACOLOGY; 1385; -. DR SwissLipids; SLP:000000669; -. DR iPTMnet; P09917; -. DR PhosphoSitePlus; P09917; -. DR BioMuta; ALOX5; -. DR DMDM; 126407; -. DR jPOST; P09917; -. DR MassIVE; P09917; -. DR MaxQB; P09917; -. DR PaxDb; 9606-ENSP00000363512; -. DR PeptideAtlas; P09917; -. DR ProteomicsDB; 52278; -. [P09917-1] DR ProteomicsDB; 7233; -. DR Pumba; P09917; -. DR Antibodypedia; 3906; 884 antibodies from 45 providers. DR DNASU; 240; -. DR Ensembl; ENST00000374391.7; ENSP00000363512.2; ENSG00000012779.12. [P09917-1] DR Ensembl; ENST00000542434.5; ENSP00000437634.1; ENSG00000012779.12. [P09917-2] DR Ensembl; ENST00000610656.4; ENSP00000484468.1; ENSG00000275565.4. [P09917-1] DR Ensembl; ENST00000622021.4; ENSP00000479958.1; ENSG00000275565.4. [P09917-2] DR GeneID; 240; -. DR KEGG; hsa:240; -. DR MANE-Select; ENST00000374391.7; ENSP00000363512.2; NM_000698.5; NP_000689.1. DR UCSC; uc001jce.5; human. [P09917-1] DR AGR; HGNC:435; -. DR CTD; 240; -. DR DisGeNET; 240; -. DR GeneCards; ALOX5; -. DR HGNC; HGNC:435; ALOX5. DR HPA; ENSG00000012779; Tissue enhanced (lung, lymphoid tissue). DR MalaCards; ALOX5; -. DR MIM; 152390; gene. DR neXtProt; NX_P09917; -. DR OpenTargets; ENSG00000012779; -. DR PharmGKB; PA46; -. DR VEuPathDB; HostDB:ENSG00000012779; -. DR eggNOG; ENOG502QQSP; Eukaryota. DR GeneTree; ENSGT00940000156111; -. DR HOGENOM; CLU_004282_3_3_1; -. DR InParanoid; P09917; -. DR OMA; MMFNAND; -. DR OrthoDB; 999249at2759; -. DR PhylomeDB; P09917; -. DR TreeFam; TF105320; -. DR BioCyc; MetaCyc:HS00336-MONOMER; -. DR BRENDA; 1.13.11.34; 2681. DR PathwayCommons; P09917; -. DR Reactome; R-HSA-2142688; Synthesis of 5-eicosatetraenoic acids. DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX). DR Reactome; R-HSA-2142700; Synthesis of Lipoxins (LX). DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-9012546; Interleukin-18 signaling. DR Reactome; R-HSA-9018676; Biosynthesis of D-series resolvins. DR Reactome; R-HSA-9018682; Biosynthesis of maresins. DR Reactome; R-HSA-9018896; Biosynthesis of E-series 18(S)-resolvins. DR Reactome; R-HSA-9020265; Biosynthesis of aspirin-triggered D-series resolvins. DR Reactome; R-HSA-9023661; Biosynthesis of E-series 18(R)-resolvins. DR Reactome; R-HSA-9026286; Biosynthesis of DPAn-3-derived protectins and resolvins. DR Reactome; R-HSA-9026290; Biosynthesis of DPAn-3-derived maresins. DR Reactome; R-HSA-9026403; Biosynthesis of DPAn-3-derived 13-series resolvins. DR Reactome; R-HSA-9027604; Biosynthesis of electrophilic Omega-3 PUFA oxo-derivatives. DR SABIO-RK; P09917; -. DR SignaLink; P09917; -. DR SIGNOR; P09917; -. DR UniPathway; UPA00877; -. DR BioGRID-ORCS; 240; 26 hits in 1167 CRISPR screens. DR ChiTaRS; ALOX5; human. DR EvolutionaryTrace; P09917; -. DR GeneWiki; Arachidonate_5-lipoxygenase; -. DR GenomeRNAi; 240; -. DR Pharos; P09917; Tclin. DR PRO; PR:P09917; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; P09917; Protein. DR Bgee; ENSG00000012779; Expressed in blood and 97 other cell types or tissues. DR ExpressionAtlas; P09917; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0005641; C:nuclear envelope lumen; IDA:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB. DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome. DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IEA:RHEA. DR GO; GO:0004051; F:arachidonate 5-lipoxygenase activity; IDA:UniProtKB. DR GO; GO:0036403; F:arachidonate 8(S)-lipoxygenase activity; IEA:RHEA. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB. DR GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central. DR GO; GO:0036336; P:dendritic cell migration; ISS:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0051122; P:hepoxilin biosynthetic process; IBA:GO_Central. DR GO; GO:0006959; P:humoral immune response; ISS:UniProtKB. DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; IMP:UniProtKB. DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB. DR GO; GO:1901753; P:leukotriene A4 biosynthetic process; IDA:UniProtKB. DR GO; GO:0019370; P:leukotriene biosynthetic process; IDA:UniProtKB. DR GO; GO:0006691; P:leukotriene metabolic process; TAS:ProtInc. DR GO; GO:0002540; P:leukotriene production involved in inflammatory response; IEA:Ensembl. DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central. DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central. DR GO; GO:2001301; P:lipoxin biosynthetic process; IMP:UniProtKB. DR GO; GO:0019372; P:lipoxygenase pathway; IBA:GO_Central. DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome. DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISS:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB. DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; ISS:UniProtKB. DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; ISS:UniProtKB. DR GO; GO:0061044; P:negative regulation of vascular wound healing; ISS:UniProtKB. DR GO; GO:0061045; P:negative regulation of wound healing; ISS:UniProtKB. DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB. DR GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; ISS:UniProtKB. DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; ISS:UniProtKB. DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; ISS:UniProtKB. DR GO; GO:0045598; P:regulation of fat cell differentiation; ISS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB. DR GO; GO:0106014; P:regulation of inflammatory response to wounding; ISS:UniProtKB. DR GO; GO:0050796; P:regulation of insulin secretion; ISS:UniProtKB. DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB. DR CDD; cd01753; PLAT_LOX; 1. DR Gene3D; 3.10.450.60; -; 1. DR Gene3D; 2.60.60.20; PLAT/LH2 domain; 1. DR InterPro; IPR000907; LipOase. DR InterPro; IPR013819; LipOase_C. DR InterPro; IPR036226; LipOase_C_sf. DR InterPro; IPR020834; LipOase_CS. DR InterPro; IPR020833; LipOase_Fe_BS. DR InterPro; IPR001885; LipOase_mml. DR InterPro; IPR001024; PLAT/LH2_dom. DR InterPro; IPR036392; PLAT/LH2_dom_sf. DR InterPro; IPR042062; PLAT_LOX_verte. DR PANTHER; PTHR11771; LIPOXYGENASE; 1. DR PANTHER; PTHR11771:SF5; POLYUNSATURATED FATTY ACID 5-LIPOXYGENASE; 1. DR Pfam; PF00305; Lipoxygenase; 1. DR Pfam; PF01477; PLAT; 1. DR PRINTS; PR00087; LIPOXYGENASE. DR PRINTS; PR00467; MAMLPOXGNASE. DR SMART; SM00308; LH2; 1. DR SUPFAM; SSF49723; Lipase/lipooxygenase domain (PLAT/LH2 domain); 1. DR SUPFAM; SSF48484; Lipoxigenase; 1. DR PROSITE; PS00711; LIPOXYGENASE_1; 1. DR PROSITE; PS00081; LIPOXYGENASE_2; 1. DR PROSITE; PS51393; LIPOXYGENASE_3; 1. DR PROSITE; PS50095; PLAT; 1. DR Genevisible; P09917; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Calcium; Cytoplasm; Dioxygenase; KW Direct protein sequencing; Hydrolase; Iron; Leukotriene biosynthesis; KW Lipid metabolism; Membrane; Metal-binding; Nucleus; Oxidoreductase; KW Phosphoprotein; Reference proteome. FT CHAIN 1..674 FT /note="Polyunsaturated fatty acid 5-lipoxygenase" FT /id="PRO_0000220693" FT DOMAIN 2..118 FT /note="PLAT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DOMAIN 119..674 FT /note="Lipoxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 17 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 18 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 19 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 44 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 45 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 47 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 79 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 80 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 368 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21233389, FT ECO:0000269|PubMed:22516296, ECO:0007744|PDB:3O8Y, FT ECO:0007744|PDB:3V92, ECO:0007744|PDB:3V98, FT ECO:0007744|PDB:3V99" FT BINDING 373 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21233389, FT ECO:0000269|PubMed:22516296, ECO:0007744|PDB:3O8Y, FT ECO:0007744|PDB:3V92, ECO:0007744|PDB:3V98, FT ECO:0007744|PDB:3V99" FT BINDING 551 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21233389, FT ECO:0000269|PubMed:22516296, ECO:0007744|PDB:3O8Y, FT ECO:0007744|PDB:3V92, ECO:0007744|PDB:3V98, FT ECO:0007744|PDB:3V99" FT BINDING 555 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21233389, FT ECO:0000269|PubMed:22516296, ECO:0007744|PDB:3O8Y, FT ECO:0007744|PDB:3V92, ECO:0007744|PDB:3V99" FT BINDING 674 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:21233389, FT ECO:0000269|PubMed:22516296, ECO:0007744|PDB:3O8Y, FT ECO:0007744|PDB:3V92, ECO:0007744|PDB:3V98, FT ECO:0007744|PDB:3V99" FT SITE 103 FT /note="Essential for stabilizing binding to COTL1" FT /evidence="ECO:0000269|PubMed:19807693" FT MOD_RES 272 FT /note="Phosphoserine; by MAPKAPK2" FT /evidence="ECO:0000269|PubMed:11844797, FT ECO:0000269|PubMed:18978352" FT MOD_RES 524 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000269|PubMed:15280375, FT ECO:0000269|PubMed:26210919" FT VAR_SEQ 424..455 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:21098726" FT /id="VSP_053534" FT VAR_SEQ 425..533 FT /note="ANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGL FT LVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSR FT -> VHGRGGRHLLRGRPGGGGGPGAAGLRERCLRVRHAGPQVLRLPQVGQEPGAAVGVP FT DRGDLHRLRPARRGQLRPAVPGHVPRRAFYREACEGSHGPIPQEPRGHCQRDC (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:21098726" FT /id="VSP_053535" FT VAR_SEQ 485..674 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:21098726" FT /id="VSP_053536" FT VAR_SEQ 534..674 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:21098726" FT /id="VSP_053537" FT VAR_SEQ 559..615 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:21098726" FT /id="VSP_046998" FT VARIANT 254 FT /note="E -> K (decreases arachidonate 5-lipoxygenase FT activity. Increases leukotriene A4 synthase activity; FT dbSNP:rs2228065)" FT /evidence="ECO:0000269|PubMed:15308583, FT ECO:0000269|PubMed:24282679" FT /id="VAR_028018" FT VARIANT 337 FT /note="P -> S (decreases arachidonate 5-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083301" FT VARIANT 447 FT /note="A -> S (increases arachidonate 5-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083302" FT VARIANT 549 FT /note="A -> V (decreases arachidonate 5-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083303" FT VARIANT 577 FT /note="P -> L (does not affect arachidonate 5-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083304" FT VARIANT 591 FT /note="T -> M (increases arachidonate 5-lipoxygenase FT activity. Does not affect leukotriene A4 synthase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083305" FT VARIANT 656 FT /note="K -> Q (increases arachidonate 5-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083306" FT MUTAGEN 14 FT /note="W->A: Impairs interaction with DICER1; when FT associated with A-76 and A-103." FT /evidence="ECO:0000269|PubMed:19022417" FT MUTAGEN 76 FT /note="W->A: Impairs interaction with DICER1; when FT associated with A-14 and A-103." FT /evidence="ECO:0000269|PubMed:19022417" FT MUTAGEN 103 FT /note="W->A: Abolishes binding to COTL1. Impairs FT interaction with DICER; when associated with A-14 and FT A-76." FT /evidence="ECO:0000269|PubMed:19022417, FT ECO:0000269|PubMed:19807693" FT MUTAGEN 272 FT /note="S->A: Loss of phosphorylation site. Permits export FT from the nucleus." FT /evidence="ECO:0000269|PubMed:18978352" FT MUTAGEN 359 FT /note="D->N: No loss of activity." FT MUTAGEN 360 FT /note="F->W: Loss of (5S)-lipoxygenase activity; when FT associated with I-425 and M-426. Loss of (5S)-lipoxygenase FT activity; when associated with I-425; M-426 and I-604. FT Exhibits a major (15S)-lipoxygenase activity; when FT associated with I-425 and M-426. Exhibits a major FT (15S)-lipoxygenase activity; when associated with I-425; FT M-426 and I-604. Does not catalyze oxygenation of FT arachodonic acid to 5-HETE; when associated with I-425: FT M-426 and I-604. Catalyzes oxygenation of arachodonic acid FT to form mostly (15S)-HETE and (8S)-HETE but also 12-HETE; FT when associated with I-425: M-426 and I-604. Abolishes the FT LTA4-synthase activity; when associated with I-425: M-426 FT and I-604. Catalyzes oxygenation of linoleic acid to FT (13S)- and (9S)-HODE; when associated with I-425: M-426 and FT I-604. Catalyzes oxygenation of (11S)- and FT (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE FT respectively; when associated with I-425: M-426 and I-604. FT Catalyzes oxygenation of alpha-linolenic acid (ALA) to FT 13-HOTrE(n-3); when associated with I-425: M-426 and I-604. FT Catalyzes oxygenation of gamma-linolenic acid (GLA) to FT 13-HOTrE(n-6) and 10-HOTrE; when associated with I-425: FT M-426 and I-604. Catalyzes the oxygenation of FT eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when FT associated with I-425: M-426 and I-604. Catalyzes the FT oxygenation of docosahexaenoic acid (DHA) to 10- and FT 17-HDHA; when associated with I-425: M-426 and I-604. FT Exhibits a lipoxin synthase activity towards (5S)-HETE as FT major substrates followed by (5S),(15S)-DiHETE and FT (15S)-HETE; when associated with I-425: M-426 and I-604." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31664810" FT MUTAGEN 363 FT /note="H->S,N: Still some substantial activity." FT /evidence="ECO:0000269|PubMed:1939225" FT MUTAGEN 368 FT /note="H->S,N,A: No activity." FT /evidence="ECO:0000269|PubMed:1540191, FT ECO:0000269|PubMed:1939225" FT MUTAGEN 373 FT /note="H->S,N: No activity." FT /evidence="ECO:0000269|PubMed:1540191, FT ECO:0000269|PubMed:1939225" FT MUTAGEN 377 FT /note="E->Q: No activity." FT /evidence="ECO:0000269|PubMed:1540191" FT MUTAGEN 391 FT /note="H->A: No activity." FT /evidence="ECO:0000269|PubMed:1540191, FT ECO:0000269|PubMed:1939225" FT MUTAGEN 391 FT /note="H->S,N: Still some substantial activity." FT /evidence="ECO:0000269|PubMed:1540191, FT ECO:0000269|PubMed:1939225" FT MUTAGEN 400 FT /note="H->A: No activity." FT /evidence="ECO:0000269|PubMed:1540191, FT ECO:0000269|PubMed:1939225" FT MUTAGEN 400 FT /note="H->S,N: Still some substantial activity." FT /evidence="ECO:0000269|PubMed:1540191, FT ECO:0000269|PubMed:1939225" FT MUTAGEN 425 FT /note="A->I: Loss of (5S)-lipoxygenase activity; when FT associated with W-360 and M-426. Loss of (5S)-lipoxygenase FT activity; when associated with W-360; M-426 and I-604. FT Exhibits a major (15S)-lipoxygenase activity; when FT associated with W-360 and M-426. Exhibits a major FT (15S)-lipoxygenase activity; when associated with W-360; FT M-426 and I-604. Does not catalyze oxygenation of FT arachodonic acid to 5-HETE; when associated with W-360; FT M-426 and I-604. Catalyzes oxygenation of arachodonic acid FT to form in majority (15S)-HETE and (8S)-HETE but also FT 12-HETE; when associated with W-360; M-426 and I-604. FT Abolishes the LTA4-synthase activity; when associated with FT W-360; M-426 and I-604. Catalyzes oxygenation of linoleic FT acid to (13S)- and (9S)-HODE; when associated with W-360; FT M-426 and I-604. Catalyzes oxygenation of (11S)- and FT (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE FT respectively; when associated with W-360; M-426 and I-604. FT Catalyzes oxygenation of alpha-linolenic acid (ALA) to FT 13-HOTrE(n-3); when associated with W-360; M-426 and I-604. FT Catalyzes oxygenation of gamma-linolenic acid (GLA) to FT 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; FT M-426 and I-604. Catalyzes the oxygenation of FT eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when FT associated with W-360; M-426 and I-604. Catalyzes the FT oxygenation of docosahexaenoic acid (DHA) to 10- and FT 17-HDHA; when associated with W-360; M-426 and I-604. FT Exhibits a lipoxin synthase activity towards (5S)-HETE as FT major substrates followed by (5S),(15S)-DiHETE and FT (15S)-HETE; when associated with W-360; M-426 and I-604." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31664810" FT MUTAGEN 426 FT /note="N->M: Loss of (5S)-lipoxygenase activity; when FT associated with W-360 and I-425. Loss of (5S)-lipoxygenase FT activity; when associated with W-360; I-425 and I-604. FT Exhibits a major (15S)-lipoxygenase activity; when FT associated with W-360 and I-425. Exhibits a major FT (15S)-lipoxygenase activity; when associated with W-360; FT I-425 and I-604. Does not catalyze oxygenation of FT arachodonic acid to 5-HETE; when associated with W-360; FT I-425 and I-604. Catalyzes oxygenation of arachodonic acid FT to form in majority (15S)-HETE and (8S)-HETE but also FT 12-HETE; when associated with W-360; I-425 and I-604. FT Abolishes the LTA4-synthase activity; when associated with FT W-360; I-425 and I-604. Catalyzes oxygenation of linoleic FT acid to (13S)- and (9S)-HODE; when associated with W-360; FT I-425 and I-604. Catalyzes oxygenation of (11S)- and FT (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE FT respectively; when associated with W-360; I-425 and I-604. FT Catalyzes oxygenation of alpha-linolenic acid (ALA) to FT 13-HOTrE(n-3); when associated with W-360; I-425 and I-604. FT Catalyzes oxygenation of gamma-linolenic acid (GLA) to FT 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; FT I-425 and I-604. Catalyzes the oxygenation of FT eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when FT associated with W-360; I-425 and I-604. Catalyzes the FT oxygenation of docosahexaenoic acid (DHA) to 10- and FT 17-HDHA; when associated with W-360; I-425 and I-604. FT Exhibits a lipoxin synthase activity towards (5S)-HETE as FT major substrates followed by (5S),(15S)-DiHETE and FT (15S)-HETE; when associated with W-360; I-425 and I-604." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31664810" FT MUTAGEN 433 FT /note="H->N,A: Almost no loss of activity." FT MUTAGEN 524 FT /note="S->A: Prevents phosphorylation by PKA." FT /evidence="ECO:0000269|PubMed:15280375" FT MUTAGEN 551 FT /note="H->N,A: No activity." FT /evidence="ECO:0000269|PubMed:1540191" FT MUTAGEN 604 FT /note="A->I: Loss of (5S)-lipoxygenase activity. Loss of FT (5S)-lipoxygenase activity; when associated with W-360; FT I-425 and M-426. Exhibits a major (15S)-lipoxygenase FT activity;when associated with W-360; I-425 and M-426. Does FT not catalyze oxygenation of arachodonic acid to 5-HETE; FT when associated with W-360; I-425 and M-426. Catalyzes FT oxygenation of arachodonic acid to form in majority FT (15S)-HETE and (8S)-HETE but also 12-HETE; when associated FT with W-360; I-425 and M-426. Abolishes the LTA4-synthase FT activity; when associated with W-360; I-425 and M-426. FT Catalyzes oxygenation of linoleic acid to (13S)- and (9 FT S)-HODE; when associated with W-360; I-425 and M-426. FT Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic FT acid to 9-HODE and (13S)-HODE respectively; when associated FT with W-360; I-425 and M-426. Catalyzes oxygenation of FT alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when FT associated with W-360; I-425 and M-426. Catalyzes FT oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) FT and 10-HOTrE; when associated with W-360; I-425 and M-426. FT Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to FT 12- and 15-HEPA; when associated with W-360; I-425 and FT M-426. Catalyzes the oxygenation of docosahexaenoic acid FT (DHA) to 10- and 17-HDHA; when associated with W-360; I-425 FT and M-426. Exhibits a lipoxin synthase activity towards FT (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE FT and (15S)-HETE; when associated with W-360; I-425 and FT M-426." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31664810" FT MUTAGEN 664 FT /note="S->A: Does not affect arachidonate 5-lipoxygenase FT activity. Does not oxygenate arachidonate typical FT 15-lipoxygenase substrates such as dihomo-gamma-linolenic FT acid and N-arachidonyl glycine." FT /evidence="ECO:0000269|PubMed:22516296" FT MUTAGEN 664 FT /note="S->D: Enhances affinity for arachidonic acid. FT Impairs arachidonate 5-lipoxygenase activity. Induces FT arachidonate 15-lipoxygenase activity. Oxygenates typical FT arachidonate 15-lipoxygenase substrates such as FT dihomo-gamma-linolenic acid and N-arachidonyl glycine. FT Synthesizes lipoxin A4 when incubated with a stable FT 5-lipoxygenase." FT /evidence="ECO:0000269|PubMed:22516296" FT STRAND 4..10 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 20..28 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 36..38 FT /evidence="ECO:0007829|PDB:7TTJ" FT STRAND 51..56 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 64..73 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 81..89 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 95..104 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:3V98" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 120..122 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 126..142 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 161..163 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 171..176 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 178..188 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 192..194 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 196..198 FT /evidence="ECO:0007829|PDB:7TTJ" FT HELIX 205..212 FT /evidence="ECO:0007829|PDB:7TTK" FT TURN 213..215 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 218..226 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 230..239 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 260..263 FT /evidence="ECO:0007829|PDB:7TTK" FT TURN 264..266 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 273..279 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 282..286 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 288..290 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 297..300 FT /evidence="ECO:0007829|PDB:3V99" FT HELIX 303..306 FT /evidence="ECO:0007829|PDB:3V99" FT STRAND 310..315 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 321..331 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 334..336 FT /evidence="ECO:0007829|PDB:7TTL" FT HELIX 345..365 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 366..372 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 373..386 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 392..397 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 398..400 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 404..414 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 421..423 FT /evidence="ECO:0007829|PDB:7TTK" FT TURN 427..431 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 432..441 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 447..449 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 451..457 FT /evidence="ECO:0007829|PDB:7TTK" FT TURN 463..465 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 470..493 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 497..502 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 504..515 FT /evidence="ECO:0007829|PDB:7TTK" FT TURN 516..520 FT /evidence="ECO:0007829|PDB:3V98" FT HELIX 522..524 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 533..547 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 549..555 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 558..562 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 565..567 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 572..574 FT /evidence="ECO:0007829|PDB:3O8Y" FT STRAND 579..581 FT /evidence="ECO:0007829|PDB:3V98" FT HELIX 585..591 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 595..608 FT /evidence="ECO:0007829|PDB:7TTK" FT HELIX 629..654 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 656..658 FT /evidence="ECO:0007829|PDB:6NCF" FT HELIX 665..667 FT /evidence="ECO:0007829|PDB:7TTK" FT STRAND 669..671 FT /evidence="ECO:0007829|PDB:7TTK" SQ SEQUENCE 674 AA; 77983 MW; 36F38C0A9E86BB21 CRC64; MPSYTVTVAT GSQWFAGTDD YIYLSLVGSA GCSEKHLLDK PFYNDFERGA VDSYDVTVDE ELGEIQLVRI EKRKYWLNDD WYLKYITLKT PHGDYIEFPC YRWITGDVEV VLRDGRAKLA RDDQIHILKQ HRRKELETRQ KQYRWMEWNP GFPLSIDAKC HKDLPRDIQF DSEKGVDFVL NYSKAMENLF INRFMHMFQS SWNDFADFEK IFVKISNTIS ERVMNHWQED LMFGYQFLNG CNPVLIRRCT ELPEKLPVTT EMVECSLERQ LSLEQEVQQG NIFIVDFELL DGIDANKTDP CTLQFLAAPI CLLYKNLANK IVPIAIQLNQ IPGDENPIFL PSDAKYDWLL AKIWVRSSDF HVHQTITHLL RTHLVSEVFG IAMYRQLPAV HPIFKLLVAH VRFTIAINTK AREQLICECG LFDKANATGG GGHVQMVQRA MKDLTYASLC FPEAIKARGM ESKEDIPYYF YRDDGLLVWE AIRTFTAEVV DIYYEGDQVV EEDPELQDFV NDVYVYGMRG RKSSGFPKSV KSREQLSEYL TVVIFTASAQ HAAVNFGQYD WCSWIPNAPP TMRAPPPTAK GVVTIEQIVD TLPDRGRSCW HLGAVWALSQ FQENELFLGM YPEEHFIEKP VKEAMARFRK NLEAIVSVIA ERNKKKQLPY YYLSPDRIPN SVAI //