LOX5_HUMAN
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 03-AUG-2022, entry version 220.
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=(5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + 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;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00726,
CC 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 (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-
CC eicosatetraenoate {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 (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-
CC eicosatetraenoate (in the presence of 200 uM ATP)
CC {ECO:0000269|PubMed:24893149};
CC Vmax=0.1 umol/min/mg enzyme toward (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-
CC eicosatetraenoate (generated in situ from arachidonic acid)
CC {ECO:0000269|PubMed:24893149};
CC Vmax=2 umol/min/mg enzyme toward (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-
CC eicosatetraenoate (generated in situ from arachidonic acid in the
CC presence of 200 uM ATP) {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="http://atlasgeneticsoncology.org/Genes/ALOX5ID42985ch10q11.html";
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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 PDBsum; 3O8Y; -.
DR PDBsum; 3V92; -.
DR PDBsum; 3V98; -.
DR PDBsum; 3V99; -.
DR PDBsum; 6N2W; -.
DR PDBsum; 6NCF; -.
DR AlphaFoldDB; P09917; -.
DR SMR; P09917; -.
DR BioGRID; 106741; 104.
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; 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; P09917; -.
DR PeptideAtlas; P09917; -.
DR PRIDE; P09917; -.
DR ProteomicsDB; 52278; -. [P09917-1]
DR ProteomicsDB; 7233; -.
DR Antibodypedia; 3906; 803 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 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; DFHMHQT; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; P09917; -.
DR TreeFam; TF105320; -.
DR BioCyc; MetaCyc:HS00336-MON; -.
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; 25 hits in 1076 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 96 other tissues.
DR ExpressionAtlas; P09917; baseline and differential.
DR Genevisible; P09917; HS.
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:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
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 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; PTHR11771; 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; SSF48484; SSF48484; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
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 A-
FT 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 (15S)-
FT lipoxygenase activity; when associated with I-425; M-426
FT and I-604. Does not catalyze oxygenation of arachodonic
FT acid to 5-HETE; when associated with I-425: M-426 and I-
FT 604. Catalyzes oxygenation of arachodonic acid to form
FT mostly (15S)-HETE and (8S)-HETE but also 12-HETE; when
FT associated with I-425: M-426 and I-604. Abolishes the LTA4-
FT synthase activity; when associated with I-425: M-426 and I-
FT 604. Catalyzes oxygenation of linoleic acid to (13S)- and
FT (9S)-HODE; when associated with I-425: M-426 and I-604.
FT Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic
FT acid to 9-HODE and (13S)-HODE respectively; when associated
FT with I-425: M-426 and I-604. Catalyzes oxygenation of
FT alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when
FT associated with I-425: M-426 and I-604. Catalyzes
FT oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6)
FT and 10-HOTrE; when associated with I-425: M-426 and I-604.
FT Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to
FT 12- and 15-HEPA; when associated with I-425: M-426 and I-
FT 604. Catalyzes the oxygenation of docosahexaenoic acid
FT (DHA) to 10- and 17-HDHA; when associated with I-425: M-426
FT and I-604. Exhibits a lipoxin synthase activity towards
FT (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE
FT and (15S)-HETE; when associated with I-425: M-426 and I-
FT 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 (15S)-
FT lipoxygenase activity; when associated with W-360; M-426
FT and I-604. Does not catalyze oxygenation of arachodonic
FT acid to 5-HETE; when associated with W-360; M-426 and I-
FT 604. Catalyzes oxygenation of arachodonic acid to form in
FT majority (15S)-HETE and (8S)-HETE but also 12-HETE; when
FT associated with W-360; M-426 and I-604. Abolishes the LTA4-
FT synthase activity; when associated with W-360; M-426 and I-
FT 604. Catalyzes oxygenation of linoleic acid to (13S)- and
FT (9S)-HODE; when associated with W-360; M-426 and I-604.
FT Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic
FT acid to 9-HODE and (13S)-HODE respectively; when associated
FT with W-360; M-426 and I-604. Catalyzes oxygenation of
FT alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when
FT associated with W-360; M-426 and I-604. Catalyzes
FT oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6)
FT and 10-HOTrE; when associated with W-360; M-426 and I-604.
FT Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to
FT 12- and 15-HEPA; when associated with W-360; M-426 and I-
FT 604. Catalyzes the oxygenation of docosahexaenoic acid
FT (DHA) to 10- and 17-HDHA; when associated with W-360; M-426
FT and I-604. 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; M-426 and I-
FT 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 (15S)-
FT lipoxygenase activity; when associated with W-360; I-425
FT and I-604. Does not catalyze oxygenation of arachodonic
FT acid to 5-HETE; when associated with W-360; I-425 and I-
FT 604. Catalyzes oxygenation of arachodonic acid to form in
FT majority (15S)-HETE and (8S)-HETE but also 12-HETE; when
FT associated with W-360; I-425 and I-604. Abolishes the LTA4-
FT synthase activity; when associated with W-360; I-425 and I-
FT 604. Catalyzes oxygenation of linoleic acid to (13S)- and
FT (9S)-HODE; when associated with W-360; I-425 and I-604.
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 I-604. Catalyzes oxygenation of
FT alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when
FT associated with W-360; I-425 and I-604. 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 I-604.
FT Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to
FT 12- and 15-HEPA; when associated with W-360; I-425 and I-
FT 604. Catalyzes the oxygenation of docosahexaenoic acid
FT (DHA) to 10- and 17-HDHA; when associated with W-360; I-425
FT and I-604. 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 I-
FT 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; I-
FT 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 (15S)-
FT HETE and (8S)-HETE but also 12-HETE; when associated with
FT 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 S)-
FT 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 M-
FT 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 M-
FT 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 15-
FT lipoxygenase substrates such as dihomo-gamma-linolenic acid
FT 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 dihomo-
FT gamma-linolenic acid and N-arachidonyl glycine. Synthesizes
FT lipoxin A4 when incubated with a stable 5-lipoxygenase."
FT /evidence="ECO:0000269|PubMed:22516296"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 20..30
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3V99"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 64..73
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 81..89
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 95..104
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 110..113
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 126..142
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 178..188
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 205..212
FT /evidence="ECO:0007829|PDB:3V98"
FT TURN 213..215
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 218..226
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 230..239
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:3V98"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 273..278
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 282..286
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:3V98"
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:3V98"
FT STRAND 321..331
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 333..336
FT /evidence="ECO:0007829|PDB:3V92"
FT HELIX 345..365
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 366..372
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 373..386
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 392..397
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 398..400
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 404..414
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 421..423
FT /evidence="ECO:0007829|PDB:3V98"
FT TURN 427..431
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 432..441
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 451..457
FT /evidence="ECO:0007829|PDB:3V98"
FT TURN 463..465
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 470..493
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 497..501
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 504..515
FT /evidence="ECO:0007829|PDB:3V98"
FT TURN 516..520
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 522..524
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 533..547
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 549..555
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 558..562
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 565..567
FT /evidence="ECO:0007829|PDB:3V98"
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:3V98"
FT HELIX 595..608
FT /evidence="ECO:0007829|PDB:3V98"
FT HELIX 629..653
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 656..658
FT /evidence="ECO:0007829|PDB:6NCF"
FT HELIX 665..667
FT /evidence="ECO:0007829|PDB:3V98"
FT STRAND 669..671
FT /evidence="ECO:0007829|PDB:3V98"
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
