LOX12_MOUSE
ID LOX12_MOUSE Reviewed; 663 AA.
AC P39655; Q8BHG4;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 4.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX12 {ECO:0000250|UniProtKB:P18054};
DE EC=1.13.11.- {ECO:0000250|UniProtKB:P18054};
DE AltName: Full=Arachidonate (12S)-lipoxygenase {ECO:0000305|PubMed:11256953};
DE Short=12S-LOX;
DE Short=12S-lipoxygenase {ECO:0000250|UniProtKB:P18054};
DE EC=1.13.11.31 {ECO:0000269|PubMed:11256953, ECO:0000269|PubMed:8188678};
DE AltName: Full=Arachidonate (15S)-lipoxygenase {ECO:0000250|UniProtKB:P18054};
DE EC=1.13.11.33 {ECO:0000250|UniProtKB:P18054};
DE AltName: Full=Linoleate (13S)-lipoxygenase {ECO:0000305|PubMed:11256953};
DE AltName: Full=Lipoxin synthase 12-LO;
DE EC=3.3.2.-;
DE AltName: Full=Platelet-type lipoxygenase 12;
DE Short=P-12LO;
GN Name=Alox12; Synonyms=Alox12p;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-663,
RP TISSUE SPECIFICITY, AND FUNCTION.
RC STRAIN=C57BL/6J, and ICR; TISSUE=Spleen;
RX PubMed=8188678; DOI=10.1016/s0021-9258(17)36743-1;
RA Chen X.-S., Kurre U., Jenkins N.A., Copeland N.G., Funk C.D.;
RT "cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic
RT structure, and chromosomal localizations of murine 12-lipoxygenases.";
RL J. Biol. Chem. 269:13979-13987(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7576099; DOI=10.1002/mc.2940140208;
RA Krieg P., Kinzig A., Ress-Loschke M., Vogel S., Vanlandingham B.,
RA Stephan M., Lehmann W.D., Marks F., Furstenberger G.;
RT "12-lipoxygenase isoenzymes in mouse skin tumor development.";
RL Mol. Carcinog. 14:118-129(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Ovary, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 126-218.
RC TISSUE=Lung;
RX PubMed=7792391; DOI=10.1016/0090-6980(94)00005-h;
RA Hagmann W., Gao X., Zacharek A., Wojciechowski L.A., Honn K.V.;
RT "12-lipoxygenase in Lewis lung carcinoma cells: molecular identity,
RT intracellular distribution of activity and protein, and Ca(2+)-dependent
RT translocation from cytosol to membranes.";
RL Prostaglandins 49:49-62(1995).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=7868854; DOI=10.1177/43.3.7868854;
RA Nakamura M., Ueda N., Kishimoto K., Yoshimoto T., Yamamoto S., Ishimura K.;
RT "Immunocytochemical localization of platelet-type arachidonate 12-
RT lipoxygenase in mouse blood cells.";
RL J. Histochem. Cytochem. 43:237-244(1995).
RN [7]
RP FUNCTION IN PLATELET ACTIVATION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=9501222; DOI=10.1073/pnas.95.6.3100;
RA Johnson E.N., Brass L.F., Funk C.D.;
RT "Increased platelet sensitivity to ADP in mice lacking platelet-type 12-
RT lipoxygenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3100-3105(1998).
RN [8]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=10383730; DOI=10.1046/j.1523-1747.1999.00595.x;
RA Johnson E.N., Nanney L.B., Virmani J., Lawson J.A., Funk C.D.;
RT "Basal transepidermal water loss is increased in platelet-type 12-
RT lipoxygenase deficient mice.";
RL J. Invest. Dermatol. 112:861-865(1999).
RN [9]
RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11256953; DOI=10.1042/0264-6021:3550097;
RA Siebert M., Krieg P., Lehmann W.D., Marks F., Fuerstenberger G.;
RT "Enzymic characterization of epidermis-derived 12-lipoxygenase
RT isoenzymes.";
RL Biochem. J. 355:97-104(2001).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=25293588; DOI=10.1194/jlr.m054072;
RA Teder T., Boeglin W.E., Brash A.R.;
RT "Lipoxygenase-catalyzed transformation of epoxy fatty acids to hydroxy-
RT endoperoxides: a potential P450 and lipoxygenase interaction.";
RL J. Lipid Res. 55:2587-2596(2014).
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:8188678, PubMed:11256953,
CC PubMed:25293588). Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-
CC eicosatetraenoate) to the specific bioactive lipid (12S)-
CC hydroperoxyeicosatetraenoate/(12S)-HPETE (PubMed:8188678,
CC PubMed:11256953). Through the production of bioactive lipids like
CC (12S)-HPETE it regulates different biological processes including
CC platelet activation (PubMed:9501222). 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. Furthermore, it may participate in
CC the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate) to generate specialized pro-resolving mediators
CC (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that
CC actively down-regulate the immune response and have anti-aggregation
CC properties with platelets (By similarity). An additional function
CC involves a multistep process by which it transforms leukotriene A4/LTA4
CC into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are
CC vasoactive and LXA4 may regulate neutrophil function via occupancy of
CC specific recognition sites (By similarity). Can also peroxidize
CC linoleate ((9Z,12Z)-octadecadienoate) to (13S)-
CC hydroperoxyoctadecadienoate/ (13S-HPODE) (PubMed:11256953). 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. Important for cell survival, as it may play
CC a role not only in proliferation but also in the prevention of
CC apoptosis in vascular smooth muscle cells (By similarity).
CC {ECO:0000250|UniProtKB:P18054, ECO:0000269|PubMed:11256953,
CC ECO:0000269|PubMed:25293588, ECO:0000269|PubMed:8188678,
CC ECO:0000269|PubMed:9501222}.
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:11256953,
CC ECO:0000269|PubMed:8188678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC Evidence={ECO:0000269|PubMed:8188678};
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:0000305|PubMed:11256953};
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:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
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:0000269|PubMed:11256953};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41325;
CC Evidence={ECO:0000305|PubMed:11256953};
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:11256953};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41329;
CC Evidence={ECO:0000305|PubMed:11256953};
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:11256953};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333;
CC Evidence={ECO:0000305|PubMed:11256953};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64725;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64729;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000269|PubMed:25293588};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50277;
CC Evidence={ECO:0000305|PubMed:25293588};
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:0000269|PubMed:25293588};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50285;
CC Evidence={ECO:0000305|PubMed:25293588};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53533;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50185;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50173;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50181;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50177;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50189;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50169;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50161;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50157;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48705;
CC Evidence={ECO:0000250|UniProtKB:P18054};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Note=Binds 1 Fe cation per subunit.;
CC -!- ACTIVITY REGULATION: Activated by EGF. Arachidonic acid conversion is
CC inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate
CC (13S,14S-epoxy-DHA) (By similarity). Arachidonate 12-lipoxygenase
CC activity is decreased when PH decreases from 7.4 to 6
CC (PubMed:11256953). {ECO:0000250|UniProtKB:P18054,
CC ECO:0000269|PubMed:11256953}.
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:7868854}.
CC Membrane {ECO:0000250}. Note=Membrane association is stimulated by EGF.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Found primarily in platelets and in microsomal and
CC cytosolic fractions of the epidermis (at protein level).
CC {ECO:0000269|PubMed:10383730, ECO:0000269|PubMed:8188678,
CC ECO:0000269|PubMed:9501222}.
CC -!- DISRUPTION PHENOTYPE: Mice are fertile and appear to exhibit no gross
CC abnormalities. However, they display increased aggregation of platelets
CC in response to ADP. They also display a mild basal transepidermal water
CC loss. {ECO:0000269|PubMed:10383730, ECO:0000269|PubMed:9501222}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
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DR EMBL; U04334; AAA20659.1; -; mRNA.
DR EMBL; S80446; AAB36013.1; -; mRNA.
DR EMBL; AK036898; BAC29629.1; -; mRNA.
DR EMBL; AK087724; BAC39981.1; -; mRNA.
DR EMBL; AL669869; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; S77511; AAB34667.1; -; mRNA.
DR CCDS; CCDS24942.1; -.
DR PIR; A54075; A54075.
DR RefSeq; NP_001318047.1; NM_001331118.1.
DR RefSeq; NP_031466.2; NM_007440.5.
DR AlphaFoldDB; P39655; -.
DR SMR; P39655; -.
DR STRING; 10090.ENSMUSP00000000329; -.
DR BindingDB; P39655; -.
DR ChEMBL; CHEMBL3225; -.
DR SwissLipids; SLP:000000684; -.
DR iPTMnet; P39655; -.
DR PhosphoSitePlus; P39655; -.
DR MaxQB; P39655; -.
DR PaxDb; P39655; -.
DR PRIDE; P39655; -.
DR ProteomicsDB; 290139; -.
DR Antibodypedia; 2760; 253 antibodies from 28 providers.
DR DNASU; 11684; -.
DR Ensembl; ENSMUST00000000329; ENSMUSP00000000329; ENSMUSG00000000320.
DR GeneID; 11684; -.
DR KEGG; mmu:11684; -.
DR UCSC; uc007juj.1; mouse.
DR CTD; 239; -.
DR MGI; MGI:87998; Alox12.
DR VEuPathDB; HostDB:ENSMUSG00000000320; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR GeneTree; ENSGT00940000155191; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; P39655; -.
DR OMA; CMDHWKE; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; P39655; -.
DR TreeFam; TF105320; -.
DR Reactome; R-MMU-2142696; Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
DR Reactome; R-MMU-2142700; Synthesis of Lipoxins (LX).
DR Reactome; R-MMU-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-MMU-9018677; Biosynthesis of DHA-derived SPMs.
DR Reactome; R-MMU-9025106; Biosynthesis of DPAn-6 SPMs.
DR Reactome; R-MMU-9026290; Biosynthesis of DPAn-3-derived maresins.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 11684; 7 hits in 73 CRISPR screens.
DR PRO; PR:P39655; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P39655; protein.
DR Bgee; ENSMUSG00000000320; Expressed in blood and 138 other tissues.
DR ExpressionAtlas; P39655; baseline and differential.
DR Genevisible; P39655; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; ISS: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; IMP: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:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0071396; P:cellular response to lipid; IEA:Ensembl.
DR GO; GO:0061436; P:establishment of skin barrier; IMP: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; ISS:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; ISS:UniProtKB.
DR GO; GO:2001306; P:lipoxin B4 biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:1905956; P:positive regulation of endothelial tube morphogenesis; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0033559; P:unsaturated fatty acid metabolic process; ISO:MGI.
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 Cytoplasm; Dioxygenase; Fatty acid metabolism; Hydrolase; Iron;
KW Lipid metabolism; Membrane; Metal-binding; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..663
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX12"
FT /id="PRO_0000220683"
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 /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 365
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 540
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
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 MUTAGEN 663
FT /note="I->D,R,K,G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:8188678"
FT MUTAGEN 663
FT /note="I->S,N: Little activity (8-15%)."
FT /evidence="ECO:0000269|PubMed:8188678"
FT MUTAGEN 663
FT /note="I->V: Nearly full activity."
FT /evidence="ECO:0000269|PubMed:8188678"
FT CONFLICT 3
FT /note="R -> A (in Ref. 1; AAA20659)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="T -> Q (in Ref. 1; AAA20659 and 2; AAB36013)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="S -> T (in Ref. 1; AAA20659 and 2; AAB36013)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 663 AA; 75390 MW; 205BE32BE2CF3E87 CRC64;
MGRYRVRVVT GAWLFSGSLN LVRLWLVGEH REAKLELQLR PARGKEEEFD FDVPEDLGPL
QFVKLHKQHT VVDDAWFCNL ITVQGPGTSA EAVFPCYRWV QGEGILSLPE GTARLAGDNA
LDVFQKYREK ELKERQQTYC WATWKEGLPQ TIAADCKDDL PPNMRFHEEK RLDFEWTLKA
GVLEMGLKRV YTLLRSWNHL EDFDQIFWGQ KSALAEKVHQ CWQEDELFGY QFLNGANPML
LRRSTSLPSR LVLPSGMEEL QAQLEKELKN GSLFEADFIL LDGIPANVIR GEPQYLAAPL
VMLRMDPGGK LLPMAIQIQP PNPSSPAPTL FLPSDPPLAW LLAKIWVRNS DFQLQELQFH
LLNTHLVAEV IAVATMRCLP GLHPIFKLLV PHIRYTMEIN TRSRTQLISD GGIFDQVVST
GGGGHVQLLT RAVAQLTYHS LCPPDDLANR GLLRIPSALY ARDALQLWEV TARYVKGMVH
LFYQSDDIVR GDPELQAWCR EITEVGLCHA QDRGFPVSFQ SRAQLCHFLT MCVFTCTAQH
AAINQGQLDW YGWVPNAPCT MRMPPPTSKD DVTMETVMGS LPDVQKACLQ MTITWHLGRL
QPDMVPLGHH TEKYFSDPRT KAVLSQFQAD LDNLEKEITA RNEQLDLPYE YLKPSRIENS
ITI
