LOX12_HUMAN
ID LOX12_HUMAN Reviewed; 663 AA.
AC P18054; O95569; Q6ISF8; Q9UQM4;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 4.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX12 {ECO:0000305};
DE EC=1.13.11.- {ECO:0000269|PubMed:17493578};
DE AltName: Full=Arachidonate (12S)-lipoxygenase {ECO:0000305|PubMed:17493578};
DE Short=12S-LOX;
DE Short=12S-lipoxygenase {ECO:0000303|PubMed:23578768};
DE EC=1.13.11.31 {ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:22984144, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:8500694};
DE AltName: Full=Arachidonate (15S)-lipoxygenase {ECO:0000305|PubMed:17493578};
DE EC=1.13.11.33 {ECO:0000269|PubMed:17493578};
DE AltName: Full=Linoleate (13S)-lipoxygenase {ECO:0000250|UniProtKB:P39655};
DE AltName: Full=Lipoxin synthase 12-LO;
DE EC=3.3.2.-;
DE AltName: Full=Platelet-type lipoxygenase 12;
GN Name=ALOX12 {ECO:0000312|HGNC:HGNC:429}; Synonyms=12LO, LOG12;
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], AND VARIANT SER-322.
RX PubMed=2244907; DOI=10.1016/0006-291x(90)91580-l;
RA Yoshimoto T., Yamamoto Y., Arakawa T., Suzuki H., Yamamoto S., Yokoyama C.,
RA Tanabe T., Toh H.;
RT "Molecular cloning and expression of human arachidonate 12-lipoxygenase.";
RL Biochem. Biophys. Res. Commun. 172:1230-1235(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-322.
RX PubMed=2377602; DOI=10.1073/pnas.87.15.5638;
RA Funk C.D., Furci L., Fitzgerald G.A.;
RT "Molecular cloning, primary structure, and expression of the human
RT platelet/erythroleukemia cell 12-lipoxygenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:5638-5642(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-261.
RX PubMed=2217179; DOI=10.1073/pnas.87.19.7477;
RA Izumi T., Hoshiko S., Raadmark O., Samuelsson B.;
RT "Cloning of the cDNA for human 12-lipoxygenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:7477-7481(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-261; SER-322 AND
RP HIS-430.
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-261.
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112.
RX PubMed=1447217; DOI=10.1016/s0021-9258(18)35835-6;
RA Yoshimoto T., Arakawa T., Hada T., Yamamoto S., Takahashi E.;
RT "Structure and chromosomal localization of human arachidonate 12-
RT lipoxygenase gene.";
RL J. Biol. Chem. 267:24805-24809(1992).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45.
RX PubMed=1570320; DOI=10.1073/pnas.89.9.3962;
RA Funk C.D., Funk L.B., Fitzgerald G.A., Samuelsson B.;
RT "Characterization of human 12-lipoxygenase genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:3962-3966(1992).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 340-427.
RC TISSUE=Skin;
RX PubMed=8304420; DOI=10.1152/ajpcell.1994.266.1.c243;
RA Hussain H., Shornick L.P., Shannon V.R., Wilson J.D., Funk C.D.,
RA Pentland A.P., Holtzman M.J.;
RT "Epidermis contains platelet-type 12-lipoxygenase that is overexpressed in
RT germinal layer keratinocytes in psoriasis.";
RL Am. J. Physiol. 266:C243-C253(1994).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 531-663.
RA Persson A.E., Lundeberg J., Uhlen M.;
RT "EU-IMAGE: full-insert length sequencing of human cDNA clones.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP CATALYTIC ACTIVITY, PATHWAY, SUBSTRATE SPECIFICITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND FUNCTION.
RX PubMed=1851637; DOI=10.1016/0005-2760(91)90128-5;
RA Hada T., Ueda N., Takahashi Y., Yamamoto S.;
RT "Catalytic properties of human platelet 12-lipoxygenase as compared with
RT the enzymes of other origins.";
RL Biochim. Biophys. Acta 1083:89-93(1991).
RN [12]
RP FUNCTION IN LIPOXIN SYNTHESIS, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND REACTION MECHANISM.
RX PubMed=8250832; DOI=10.1042/bj2960127;
RA Romano M., Chen X.S., Takahashi Y., Yamamoto S., Funk C.D., Serhan C.N.;
RT "Lipoxin synthase activity of human platelet 12-lipoxygenase.";
RL Biochem. J. 296:127-133(1993).
RN [13]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=8319693; DOI=10.1111/j.1432-1033.1993.tb17988.x;
RA Chen X.S., Brash A.R., Funk C.D.;
RT "Purification and characterization of recombinant histidine-tagged human
RT platelet 12-lipoxygenase expressed in a baculovirus/insect cell system.";
RL Eur. J. Biochem. 214:845-852(1993).
RN [14]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF HIS-355; HIS-360; HIS-365; HIS-383;
RP HIS-392; LYS-416; ALA-417; VAL-418 AND HIS-540, AND FUNCTION.
RX PubMed=8500694; DOI=10.1096/fasebj.7.8.8500694;
RA Chen X.S., Funk C.D.;
RT "Structure-function properties of human platelet 12-lipoxygenase: chimeric
RT enzyme and in vitro mutagenesis studies.";
RL FASEB J. 7:694-701(1993).
RN [15]
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND INDUCTION.
RX PubMed=8912711; DOI=10.1006/excr.1996.0317;
RA Hagmann W., Gao X., Timar J., Chen Y.Q., Strohmaier A.R., Fahrenkopf C.,
RA Kagawa D., Lee M., Zacharek A., Honn K.V.;
RT "12-Lipoxygenase in A431 cells: genetic identity, modulation of expression,
RT and intracellular localization.";
RL Exp. Cell Res. 228:197-205(1996).
RN [16]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=9751607;
RA Nie D., Hillman G.G., Geddes T., Tang K., Pierson C., Grignon D.J.,
RA Honn K.V.;
RT "Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates
RT angiogenesis and tumor growth.";
RL Cancer Res. 58:4047-4051(1998).
RN [17]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=16638750; DOI=10.1074/jbc.m601887200;
RA Nie D., Krishnamoorthy S., Jin R., Tang K., Chen Y., Qiao Y., Zacharek A.,
RA Guo Y., Milanini J., Pages G., Honn K.V.;
RT "Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate
RT cancer cells.";
RL J. Biol. Chem. 281:18601-18609(2006).
RN [18]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=17493578; DOI=10.1016/j.abb.2007.04.007;
RA Prusakiewicz J.J., Turman M.V., Vila A., Ball H.L., Al-Mestarihi A.H.,
RA Di Marzo V., Marnett L.J.;
RT "Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases
RT and cyclooxygenases.";
RL Arch. Biochem. Biophys. 464:260-268(2007).
RN [19]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=18311922; DOI=10.1021/bi702530z;
RA Turman M.V., Kingsley P.J., Rouzer C.A., Cravatt B.F., Marnett L.J.;
RT "Oxidative metabolism of a fatty acid amide hydrolase-regulated lipid,
RT arachidonoyltaurine.";
RL Biochemistry 47:3917-3925(2008).
RN [20]
RP INDUCTION BY UV.
RX PubMed=18755188; DOI=10.1016/j.febslet.2008.08.017;
RA Yoo H., Jeon B., Jeon M.S., Lee H., Kim T.Y.;
RT "Reciprocal regulation of 12- and 15-lipoxygenases by UV-irradiation in
RT human keratinocytes.";
RL FEBS Lett. 582:3249-3253(2008).
RN [21]
RP FUNCTION IN CELL MIGRATION.
RX PubMed=22237009; DOI=10.1016/j.yexcr.2011.12.017;
RA Klampfl T., Bogner E., Bednar W., Mager L., Massudom D., Kalny I.,
RA Heinzle C., Berger W., Staettner S., Karner J., Klimpfinger M.,
RA Fuerstenberger G., Krieg P., Marian B.;
RT "Up-regulation of 12(S)-lipoxygenase induces a migratory phenotype in
RT colorectal cancer cells.";
RL Exp. Cell Res. 318:768-778(2012).
RN [22]
RP FUNCTION IN APOPTOTIC PROCESS, AND TISSUE SPECIFICITY.
RX PubMed=23578768; DOI=10.1016/j.yexcr.2013.04.001;
RA Weisinger G., Grafi-Cohen M., Hirsh M., Knoll E., Sharon O., Many A.,
RA Limor R., Stern N.;
RT "12S-Lipoxygenase is necessary for human vascular smooth muscle cell
RT survival.";
RL Exp. Cell Res. 319:1586-1593(2013).
RN [23]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=22984144; DOI=10.1194/jlr.m026385;
RA Ikei K.N., Yeung J., Apopa P.L., Ceja J., Vesci J., Holman T.R.,
RA Holinstat M.;
RT "Investigations of human platelet-type 12-lipoxygenase: role of
RT lipoxygenase products in platelet activation.";
RL J. Lipid Res. 53:2546-2559(2012).
RN [24]
RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=23504711; DOI=10.1096/fj.13-227728;
RA Dalli J., Zhu M., Vlasenko N.A., Deng B., Haeggstroem J.Z., Petasis N.A.,
RA Serhan C.N.;
RT "The novel 13S,14S-epoxy-maresin is converted by human macrophages to
RT maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts
RT macrophage phenotype.";
RL FASEB J. 27:2573-2583(2013).
RN [25]
RP CATALYTIC ACTIVITY, FUNCTION, VARIANTS HIS-134; LYS-259; ARG-261 AND
RP SER-322, AND CHARACTERIZATION OF VARIANTS HIS-134; LYS-259; ARG-261 AND
RP SER-322.
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 [26]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25036362; DOI=10.1371/journal.pone.0102362;
RA Deng B., Wang C.W., Arnardottir H.H., Li Y., Cheng C.Y., Dalli J.,
RA Serhan C.N.;
RT "Maresin biosynthesis and identification of maresin 2, a new anti-
RT inflammatory and pro-resolving mediator from human macrophages.";
RL PLoS ONE 9:E102362-E102362(2014).
RN [27]
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 [28]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 172-662 IN COMPLEX WITH IRON IONS.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the lipoxygenase domain of human arachidonate 12-
RT lipoxygenase, 12s-type.";
RL Submitted (FEB-2009) to the PDB data bank.
RN [29]
RP VARIANT ARG-261.
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).
RN [30]
RP VARIANT ARG-261, AND INVOLVEMENT IN COLORECTAL CANCER.
RX PubMed=17151091; DOI=10.1093/carcin/bgl242;
RA Tan W., Wu J., Zhang X., Guo Y., Liu J., Sun T., Zhang B., Zhao D.,
RA Yang M., Yu D., Lin D.;
RT "Associations of functional polymorphisms in cyclooxygenase-2 and platelet
RT 12-lipoxygenase with risk of occurrence and advanced disease status of
RT colorectal cancer.";
RL Carcinogenesis 28:1197-1201(2007).
RN [31]
RP VARIANT ARG-261, AND INVOLVEMENT IN ESOPHAGEAL CANCER.
RX PubMed=17460548; DOI=10.1097/fpc.0b013e328010bda1;
RA Guo Y., Zhang X., Tan W., Miao X., Sun T., Zhao D., Lin D.;
RT "Platelet 12-lipoxygenase Arg261Gln polymorphism: functional
RT characterization and association with risk of esophageal squamous cell
RT carcinoma in combination with COX-2 polymorphisms.";
RL Pharmacogenet. Genomics 17:197-205(2007).
CC -!- FUNCTION: Catalyzes the regio and stereo-specific incorporation of
CC molecular oxygen into free and esterified polyunsaturated fatty acids
CC generating lipid hydroperoxides that can be further reduced to the
CC corresponding hydroxy species (PubMed:17493578, PubMed:1851637,
CC PubMed:8319693, PubMed:8500694, PubMed:18311922, PubMed:32404334).
CC Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the
CC specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE
CC (PubMed:17493578, PubMed:22984144, PubMed:24282679, PubMed:8319693,
CC PubMed:8500694). Through the production of bioactive lipids like (12S)-
CC HPETE it regulates different biological processes including platelet
CC activation (PubMed:8319693, PubMed:8500694). It can also catalyze the
CC epoxidation of double bonds of polyunsaturated fatty acids such as
CC (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the
CC formation of (13S,14S)-epoxy-DHA (PubMed:23504711). Furthermore, it may
CC participate in the sequential oxidations of DHA
CC ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-
CC resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and
CC (7S,14S)-diHPDHA, that actively down-regulate the immune response and
CC have anti-aggregation properties with platelets (PubMed:32404334). An
CC additional function involves a multistep process by which it transforms
CC leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and
CC lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil
CC function via occupancy of specific recognition sites (PubMed:8250832).
CC Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-
CC hydroperoxyoctadecadienoate/ (13S-HPODE) (By similarity). Due to its
CC role in regulating both the expression of the vascular endothelial
CC growth factor (VEGF, an angiogenic factor involved in the survival and
CC metastasis of solid tumors) and the expression of integrin beta-1
CC (known to affect tumor cell migration and proliferation), it can be
CC regarded as protumorigenic (PubMed:9751607, PubMed:16638750,
CC PubMed:22237009). Important for cell survival, as it may play a role
CC not only in proliferation but also in the prevention of apoptosis in
CC vascular smooth muscle cells (PubMed:23578768).
CC {ECO:0000250|UniProtKB:P39655, ECO:0000269|PubMed:16638750,
CC ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:18311922,
CC ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:22237009,
CC ECO:0000269|PubMed:22984144, ECO:0000269|PubMed:23504711,
CC ECO:0000269|PubMed:23578768, ECO:0000269|PubMed:24282679,
CC ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8250832,
CC ECO:0000269|PubMed:8319693, ECO:0000269|PubMed:8500694,
CC ECO:0000269|PubMed:9751607}.
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 EC=1.13.11.31; Evidence={ECO:0000269|PubMed:17493578,
CC ECO:0000269|PubMed:22984144, ECO:0000269|PubMed:24282679,
CC ECO:0000269|PubMed:8319693, ECO:0000269|PubMed:8500694};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC Evidence={ECO:0000305|PubMed:17493578, ECO:0000305|PubMed:22984144};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15S)-hydroperoxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:16869,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57446;
CC EC=1.13.11.33; Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H2O + 2 leukotriene A4 + O2 = 2 lipoxin A4;
CC Xref=Rhea:RHEA:48584, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57463, ChEBI:CHEBI:67026;
CC Evidence={ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48585;
CC Evidence={ECO:0000305|PubMed:8250832};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H2O + 2 leukotriene A4 + O2 = 2 lipoxin B4;
CC Xref=Rhea:RHEA:48588, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57463, ChEBI:CHEBI:67031;
CC Evidence={ECO:0000269|PubMed:8250832};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48589;
CC Evidence={ECO:0000305|PubMed:8250832};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate =
CC (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + H2O;
CC Xref=Rhea:RHEA:53532, ChEBI:CHEBI:15377, ChEBI:CHEBI:78048,
CC ChEBI:CHEBI:131958; Evidence={ECO:0000269|PubMed:23504711};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53533;
CC Evidence={ECO:0000305|PubMed:23504711};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine + O2 = N-(15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-alanine;
CC Xref=Rhea:RHEA:50184, ChEBI:CHEBI:15379, ChEBI:CHEBI:132071,
CC ChEBI:CHEBI:132077; Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50185;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine + O2 = N-(12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-alanine;
CC Xref=Rhea:RHEA:50172, ChEBI:CHEBI:15379, ChEBI:CHEBI:132071,
CC ChEBI:CHEBI:132074; Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50173;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 =
CC N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-gamma-
CC aminobutanoate; Xref=Rhea:RHEA:50180, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:132072, ChEBI:CHEBI:132078;
CC Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50181;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 =
CC N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-gamma-
CC aminobutanoate; Xref=Rhea:RHEA:50176, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:132072, ChEBI:CHEBI:132075;
CC Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50177;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-glycine;
CC Xref=Rhea:RHEA:50188, ChEBI:CHEBI:15379, ChEBI:CHEBI:59002,
CC ChEBI:CHEBI:132076; Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50189;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-glycine;
CC Xref=Rhea:RHEA:50168, ChEBI:CHEBI:15379, ChEBI:CHEBI:59002,
CC ChEBI:CHEBI:132073; Evidence={ECO:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50169;
CC Evidence={ECO:0000305|PubMed:17493578};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-taurine;
CC Xref=Rhea:RHEA:50160, ChEBI:CHEBI:15379, ChEBI:CHEBI:132060,
CC ChEBI:CHEBI:132061; Evidence={ECO:0000269|PubMed:18311922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50161;
CC Evidence={ECO:0000305|PubMed:18311922};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-taurine;
CC Xref=Rhea:RHEA:50156, ChEBI:CHEBI:15379, ChEBI:CHEBI:132060,
CC ChEBI:CHEBI:132062; Evidence={ECO:0000269|PubMed:18311922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50157;
CC Evidence={ECO:0000305|PubMed:18311922};
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:25036362,
CC ECO:0000269|PubMed:32404334};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333;
CC Evidence={ECO:0000305|PubMed:25036362, ECO:0000305|PubMed:32404334};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2
CC = (7S,14S)-dihydroperoxy-(4Z,8E,10Z,12E,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:64724, ChEBI:CHEBI:15379, ChEBI:CHEBI:156049,
CC ChEBI:CHEBI:156082; Evidence={ECO:0000269|PubMed:32404334};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64725;
CC Evidence={ECO:0000305|PubMed:32404334};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2
CC = (7S,17S)-dihydroperoxy-(4Z,8E,10Z,13Z,15E,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:64728, ChEBI:CHEBI:15379, ChEBI:CHEBI:140349,
CC ChEBI:CHEBI:156049; Evidence={ECO:0000269|PubMed:32404334};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64729;
CC Evidence={ECO:0000305|PubMed:32404334};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 12S-HpEPE;
CC Xref=Rhea:RHEA:48704, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:90772; Evidence={ECO:0000269|PubMed:22984144};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48705;
CC Evidence={ECO:0000305|PubMed:22984144};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = (12S)-hydroperoxy-
CC (8Z,10E,14Z)-eicosatrienoate; Xref=Rhea:RHEA:41328,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:78047;
CC Evidence={ECO:0000269|PubMed:22984144};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41329;
CC Evidence={ECO:0000305|PubMed:22984144};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + O2 = (13S)-hydroperoxy-(9Z,11E)-
CC octadecadienoate; Xref=Rhea:RHEA:22780, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:57466;
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22781;
CC Evidence={ECO:0000250|UniProtKB:P39655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)-hydroperoxy-
CC (5Z,8Z,10E)-eicosatrienoate; Xref=Rhea:RHEA:41324, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:78043, ChEBI:CHEBI:78046;
CC Evidence={ECO:0000250|UniProtKB:P39655};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41325;
CC Evidence={ECO:0000250|UniProtKB:P39655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)-
CC hydroperoxy-(14R,15S)-epoxy-(5Z,8Z,10E)-eicosatrienoate;
CC Xref=Rhea:RHEA:50276, ChEBI:CHEBI:15379, ChEBI:CHEBI:131965,
CC ChEBI:CHEBI:132063; Evidence={ECO:0000250|UniProtKB:P39655};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50277;
CC Evidence={ECO:0000250|UniProtKB:P39655};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)-
CC hydroperoxy-(14S,15R)-epoxy-(5Z,8Z,10E)-eicosatrienoate;
CC Xref=Rhea:RHEA:50284, ChEBI:CHEBI:15379, ChEBI:CHEBI:131964,
CC ChEBI:CHEBI:132065; Evidence={ECO:0000250|UniProtKB:P39655};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50285;
CC Evidence={ECO:0000250|UniProtKB:P39655};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Note=Binds 1 Fe cation per subunit.;
CC -!- ACTIVITY REGULATION: Activated by EGF (PubMed:8912711). Arachidonic
CC acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-
CC docosahexaenoate (13S,14S-epoxy-DHA) (PubMed:23504711). Arachidonate
CC 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6
CC (By similarity). {ECO:0000250|UniProtKB:P39655,
CC ECO:0000269|PubMed:23504711, ECO:0000269|PubMed:8912711}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 uM for arachidonate (at pH 7.0 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:1851637};
CC KM=10 uM for arachidonate (at pH 8.0 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:8319693};
CC KM=6.2 uM for arachidonate (at pH 7.4) {ECO:0000269|PubMed:8250832};
CC KM=9 uM for linoleate (at pH 8.0 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:8319693};
CC KM=7.9 uM for leukotriene A4 (at pH 7.4)
CC {ECO:0000269|PubMed:8250832};
CC KM=3 uM for eicosa-5,8,11,14,17-pentaenoate (at pH 7.0 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:1851637};
CC KM=35 uM for eicosa-8,11,14-trienoate (at pH 7.0 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:1851637};
CC KM=14.3 uM for 5,6-epoxy-8,11,14-eicosatrienoate (at pH 7.4)
CC {ECO:0000269|PubMed:8250832};
CC KM=9.5 uM for arachidonic acid {ECO:0000269|PubMed:17493578};
CC KM=10.1 uM for N-arachidonoylglycine {ECO:0000269|PubMed:17493578};
CC KM=15.7 uM for N-arachidonoyl-L-alanine
CC {ECO:0000269|PubMed:17493578};
CC KM=10.9 uM for N-arachidonoyl-gamma-aminobutyric acid
CC {ECO:0000269|PubMed:17493578};
CC KM=9.7 uM for arachidonic acid {ECO:0000269|PubMed:25036362};
CC KM=5.1 uM for docosahexaenoate {ECO:0000269|PubMed:25036362};
CC KM=12.6 uM for arachidonic acid (in presence of calcium dichloride)
CC {ECO:0000269|PubMed:25036362};
CC KM=7.1 uM for docosahexaenoate (in presence of calcium dichloride)
CC {ECO:0000269|PubMed:25036362};
CC Vmax=3 umol/min/mg enzyme with arachidonate as substrate (at pH 8.0
CC and 25 degrees Celsius) {ECO:0000269|PubMed:8319693};
CC Vmax=1.057 umol/min/mg enzyme with arachidonate as substrate (at pH
CC 7.4) {ECO:0000269|PubMed:8250832};
CC Vmax=0.0375 umol/min/mg enzyme with linoleate as substrate (at pH 8.0
CC and 25 degrees Celsius) {ECO:0000269|PubMed:8319693};
CC Vmax=0.025 umol/min/mg enzyme with leukotriene A4 as substrate (at pH
CC 7.4) {ECO:0000269|PubMed:8250832};
CC Vmax=0.985 umol/min/mg enzyme with 5,6-epoxy-8,11,14-eicosatrienoate
CC as substrate (at pH 7.4) {ECO:0000269|PubMed:8250832};
CC pH dependence:
CC Optimum pH is 7.5-8.0 (for arachidonate 12-lipoxygenase activity).
CC {ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693};
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:1851637}.
CC -!- INTERACTION:
CC P18054; P13647: KRT5; NbExp=7; IntAct=EBI-1633210, EBI-702187;
CC P18054; P02545: LMNA; NbExp=4; IntAct=EBI-1633210, EBI-351935;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Membrane. Note=Membrane
CC association is stimulated by EGF.
CC -!- TISSUE SPECIFICITY: Expressed in vascular smooth muscle cells.
CC {ECO:0000269|PubMed:23578768}.
CC -!- INDUCTION: Down-regulated upon starvation, by UV-irradiation and 15-
CC lipoxygenase metabolites. {ECO:0000269|PubMed:18755188,
CC ECO:0000269|PubMed:8912711}.
CC -!- DISEASE: Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the
CC esophagus. The most common types are esophageal squamous cell carcinoma
CC and adenocarcinoma. Cancer of the esophagus remains a devastating
CC disease because it is usually not detected until it has progressed to
CC an advanced incurable stage. {ECO:0000269|PubMed:17460548}.
CC Note=Disease susceptibility may be associated with variants affecting
CC the gene represented in this entry. Gln at position 261 may confer
CC interindividual susceptibility to esophageal cancer (PubMed:17460548).
CC {ECO:0000269|PubMed:17460548}.
CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. {ECO:0000269|PubMed:17151091}. Note=Disease
CC susceptibility may be associated with variants affecting the gene
CC represented in this entry. Gln at position 261 may confer
CC interindividual susceptibility to colorectal cancer (PubMed:17460548).
CC {ECO:0000269|PubMed:17460548}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/alox12/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ALOX12ID620ch17p13.html";
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DR EMBL; M62982; AAA51533.1; -; mRNA.
DR EMBL; M35418; AAA60056.1; -; mRNA.
DR EMBL; M58704; AAA59523.1; -; mRNA.
DR EMBL; AY527817; AAS00094.1; -; Genomic_DNA.
DR EMBL; AC040977; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC069557; AAH69557.1; -; mRNA.
DR EMBL; D12638; BAA02162.1; -; Genomic_DNA.
DR EMBL; M87004; AAA51587.1; -; Genomic_DNA.
DR EMBL; S68587; AAD14020.1; -; mRNA.
DR EMBL; AF143883; AAD32700.1; -; mRNA.
DR CCDS; CCDS11084.1; -.
DR PIR; A38283; A38283.
DR RefSeq; NP_000688.2; NM_000697.2.
DR PDB; 3D3L; X-ray; 2.60 A; A/B=172-663.
DR PDBsum; 3D3L; -.
DR AlphaFoldDB; P18054; -.
DR SMR; P18054; -.
DR BioGRID; 106740; 11.
DR IntAct; P18054; 4.
DR MINT; P18054; -.
DR STRING; 9606.ENSP00000251535; -.
DR BindingDB; P18054; -.
DR ChEMBL; CHEMBL3687; -.
DR DrugCentral; P18054; -.
DR GuidetoPHARMACOLOGY; 1387; -.
DR SwissLipids; SLP:000000670; -.
DR iPTMnet; P18054; -.
DR PhosphoSitePlus; P18054; -.
DR BioMuta; ALOX12; -.
DR DMDM; 125987838; -.
DR jPOST; P18054; -.
DR MassIVE; P18054; -.
DR PaxDb; P18054; -.
DR PeptideAtlas; P18054; -.
DR PRIDE; P18054; -.
DR ProteomicsDB; 53540; -.
DR Antibodypedia; 2760; 253 antibodies from 28 providers.
DR DNASU; 239; -.
DR Ensembl; ENST00000251535.11; ENSP00000251535.6; ENSG00000108839.12.
DR GeneID; 239; -.
DR KEGG; hsa:239; -.
DR MANE-Select; ENST00000251535.11; ENSP00000251535.6; NM_000697.3; NP_000688.2.
DR UCSC; uc002gdx.4; human.
DR CTD; 239; -.
DR DisGeNET; 239; -.
DR GeneCards; ALOX12; -.
DR HGNC; HGNC:429; ALOX12.
DR HPA; ENSG00000108839; Tissue enhanced (esophagus, vagina).
DR MIM; 114500; phenotype.
DR MIM; 133239; phenotype.
DR MIM; 152391; gene.
DR neXtProt; NX_P18054; -.
DR OpenTargets; ENSG00000108839; -.
DR PharmGKB; PA45; -.
DR VEuPathDB; HostDB:ENSG00000108839; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR GeneTree; ENSGT00940000155191; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; P18054; -.
DR OMA; CMDHWKE; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; P18054; -.
DR TreeFam; TF105320; -.
DR BioCyc; MetaCyc:HS03167-MON; -.
DR BRENDA; 1.13.11.31; 2681.
DR PathwayCommons; P18054; -.
DR Reactome; R-HSA-2142696; Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
DR Reactome; R-HSA-2142700; Synthesis of Lipoxins (LX).
DR Reactome; R-HSA-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-HSA-9018677; Biosynthesis of DHA-derived SPMs.
DR Reactome; R-HSA-9025106; Biosynthesis of DPAn-6 SPMs.
DR Reactome; R-HSA-9026290; Biosynthesis of DPAn-3-derived maresins.
DR SABIO-RK; P18054; -.
DR SignaLink; P18054; -.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 239; 9 hits in 1072 CRISPR screens.
DR ChiTaRS; ALOX12; human.
DR EvolutionaryTrace; P18054; -.
DR GeneWiki; ALOX12; -.
DR GenomeRNAi; 239; -.
DR Pharos; P18054; Tchem.
DR PRO; PR:P18054; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P18054; protein.
DR Bgee; ENSG00000108839; Expressed in lower esophagus mucosa and 114 other tissues.
DR ExpressionAtlas; P18054; baseline and differential.
DR Genevisible; P18054; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0047977; F:hepoxilin-epoxide hydrolase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; 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; IDA:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; IDA:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB.
DR GO; GO:1901751; P:leukotriene A4 metabolic process; IDA:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IDA:UniProtKB.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; IDA:UniProtKB.
DR GO; GO:2001306; P:lipoxin B4 biosynthetic process; IDA:UniProtKB.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0042554; P:superoxide anion generation; NAS:UniProtKB.
DR GO; GO:0033559; P:unsaturated fatty acid metabolic process; IDA: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; Cytoplasm; Dioxygenase; Fatty acid metabolism; Hydrolase;
KW Iron; Lipid metabolism; Membrane; Metal-binding; Oxidoreductase;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..663
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX12"
FT /id="PRO_0000220682"
FT DOMAIN 2..114
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 115..663
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 360
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 365
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 540
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 544
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 663
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1LQ70"
FT VARIANT 134
FT /note="D -> H (does not affect lipoxygenase activity;
FT dbSNP:rs114985038)"
FT /evidence="ECO:0000269|PubMed:24282679"
FT /id="VAR_082032"
FT VARIANT 259
FT /note="E -> K (does not affect lipoxygenase activity;
FT dbSNP:rs4987104)"
FT /evidence="ECO:0000269|PubMed:24282679"
FT /id="VAR_030471"
FT VARIANT 261
FT /note="Q -> R (does not affect lipoxygenase activity;
FT dbSNP:rs1126667)"
FT /evidence="ECO:0000269|PubMed:15308583,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17151091,
FT ECO:0000269|PubMed:17460548, ECO:0000269|PubMed:2217179,
FT ECO:0000269|PubMed:24282679, ECO:0000269|Ref.4"
FT /id="VAR_018743"
FT VARIANT 298
FT /note="A -> T"
FT /id="VAR_004279"
FT VARIANT 322
FT /note="N -> S (does not affect lipoxygenase activity;
FT dbSNP:rs434473)"
FT /evidence="ECO:0000269|PubMed:2244907,
FT ECO:0000269|PubMed:2377602, ECO:0000269|PubMed:24282679,
FT ECO:0000269|Ref.4"
FT /id="VAR_018744"
FT VARIANT 430
FT /note="R -> H (in dbSNP:rs11571342)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_018745"
FT MUTAGEN 355
FT /note="H->Q: No effect on arachidonate 12(S)-lipoxygenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 360
FT /note="H->Q,Y: Complete loss of arachidonate 12(S)-
FT lipoxygenase activity."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 365
FT /note="H->Q: Complete loss of arachidonate 12(S)-
FT lipoxygenase activity."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 383
FT /note="H->Q: Alteredarachidonate 12(S)-lipoxygenase
FT activity and protein expression."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 392
FT /note="H->Q: No effect on arachidonate 12(S)-lipoxygenase
FT activity."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 416
FT /note="K->Q: Reduced arachidonate 12(S)-lipoxygenase
FT activity. No effect on the stereoselectivity of the
FT oxygenation reaction."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 417
FT /note="A->I: Reduced arachidonate 12(S)-lipoxygenase
FT activity. Alters the stereoselectivity of the oxygenation
FT reaction."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 418
FT /note="V->M: No effect onarachidonate 12(S)-lipoxygenase
FT activity. No effect on the stereoselectivity of the
FT oxygenation reaction."
FT /evidence="ECO:0000269|PubMed:8500694"
FT MUTAGEN 540
FT /note="H->Q: Complete loss of arachidonate 12(S)-
FT lipoxygenase activity."
FT /evidence="ECO:0000269|PubMed:8500694"
FT CONFLICT 189..192
FT /note="RVYT -> PCLH (in Ref. 1; AAA51533)"
FT /evidence="ECO:0000305"
FT CONFLICT 345
FT /note="S -> C (in Ref. 1; AAA51533)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="L -> P (in Ref. 2; AAA60056)"
FT /evidence="ECO:0000305"
FT HELIX 182..195
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 198..200
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 203..207
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 213..221
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 225..234
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 258..269
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 300..305
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 311..319
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 337..357
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 358..364
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 365..378
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 384..389
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 390..392
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 426..434
FT /evidence="ECO:0007829|PDB:3D3L"
FT TURN 438..441
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 443..449
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 459..482
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 486..491
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 493..503
FT /evidence="ECO:0007829|PDB:3D3L"
FT TURN 504..508
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 510..512
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 522..536
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 538..544
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 547..551
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 567..571
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 574..580
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 584..597
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 618..643
FT /evidence="ECO:0007829|PDB:3D3L"
FT HELIX 654..656
FT /evidence="ECO:0007829|PDB:3D3L"
FT STRAND 657..660
FT /evidence="ECO:0007829|PDB:3D3L"
SQ SEQUENCE 663 AA; 75694 MW; C4D6D5B320666A77 CRC64;
MGRYRIRVAT GAWLFSGSYN RVQLWLVGTR GEAELELQLR PARGEEEEFD HDVAEDLGLL
QFVRLRKHHW LVDDAWFCDR ITVQGPGACA EVAFPCYRWV QGEDILSLPE GTARLPGDNA
LDMFQKHREK ELKDRQQIYC WATWKEGLPL TIAADRKDDL PPNMRFHEEK RLDFEWTLKA
GALEMALKRV YTLLSSWNCL EDFDQIFWGQ KSALAEKVRQ CWQDDELFSY QFLNGANPML
LRRSTSLPSR LVLPSGMEEL QAQLEKELQN GSLFEADFIL LDGIPANVIR GEKQYLAAPL
VMLKMEPNGK LQPMVIQIQP PNPSSPTPTL FLPSDPPLAW LLAKSWVRNS DFQLHEIQYH
LLNTHLVAEV IAVATMRCLP GLHPIFKFLI PHIRYTMEIN TRARTQLISD GGIFDKAVST
GGGGHVQLLR RAAAQLTYCS LCPPDDLADR GLLGLPGALY AHDALRLWEI IARYVEGIVH
LFYQRDDIVK GDPELQAWCR EITEVGLCQA QDRGFPVSFQ SQSQLCHFLT MCVFTCTAQH
AAINQGQLDW YAWVPNAPCT MRMPPPTTKE DVTMATVMGS LPDVRQACLQ MAISWHLSRR
QPDMVPLGHH KEKYFSGPKP KAVLNQFRTD LEKLEKEITA RNEQLDWPYE YLKPSCIENS
VTI
