ID LOX12_RAT Reviewed; 663 AA.
AC F1LQ70;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 24-JAN-2024, entry version 78.
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:23382512};
DE Short=12S-LOX;
DE Short=12S-lipoxygenase {ECO:0000250|UniProtKB:P18054};
DE EC=1.13.11.31 {ECO:0000269|PubMed:23382512};
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: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|RGD:1311159};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP FUNCTION IN APOPTOSIS.
RX PubMed=15105833; DOI=10.1038/sj.cdd.4401395;
RA Lebeau A., Terro F., Rostene W., Pelaprat D.;
RT "Blockade of 12-lipoxygenase expression protects cortical neurons from
RT apoptosis induced by beta-amyloid peptide.";
RL Cell Death Differ. 11:875-884(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=23382512; DOI=10.1096/fj.12-217414;
RA Gregus A.M., Dumlao D.S., Wei S.C., Norris P.C., Catella L.C.,
RA Meyerstein F.G., Buczynski M.W., Steinauer J.J., Fitzsimmons B.L.,
RA Yaksh T.L., Dennis E.A.;
RT "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical
RT role for spinal eLOX3 hepoxilin synthase activity in inflammatory
RT hyperalgesia.";
RL FASEB J. 27:1939-1949(2013).
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:23382512). Mainly converts
CC arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific
CC bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE. Through
CC the production of bioactive lipids like (12S)-HPETE it regulates
CC different biological processes including platelet activation. It can
CC also catalyze the epoxidation of double bonds of polyunsaturated fatty
CC acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting
CC in the formation of (13S,14S)-epoxy-DHA. 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 (By similarity). 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:23382512).
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. 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:0000250|UniProtKB:P39655,
CC ECO:0000269|PubMed:23382512}.
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:23382512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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:23382512};
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:23382512};
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=(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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = (12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z,17Z)-eicosapentaenoate;
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 -!- 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:0000250|UniProtKB:P18054};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41329;
CC Evidence={ECO:0000250|UniProtKB:P18054};
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 Evidence={ECO:0000255|PROSITE-ProRule:PRU00726};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00726};
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 (By similarity).
CC {ECO:0000250|UniProtKB:P18054, ECO:0000250|UniProtKB:P39655}.
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:23382512}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Membrane {ECO:0000250}.
CC Note=Membrane association is stimulated by EGF. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
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DR EMBL; AABR06064404; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; F1LQ70; -.
DR SMR; F1LQ70; -.
DR STRING; 10116.ENSRNOP00000034009; -.
DR iPTMnet; F1LQ70; -.
DR PhosphoSitePlus; F1LQ70; -.
DR PaxDb; 10116-ENSRNOP00000034009; -.
DR Ensembl; ENSRNOT00000033098.6; ENSRNOP00000034009.4; ENSRNOG00000027037.6.
DR UCSC; RGD:1311159; rat.
DR AGR; RGD:1311159; -.
DR RGD; 1311159; Alox12.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR GeneTree; ENSGT00940000155191; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; F1LQ70; -.
DR OMA; MEMIMAS; -.
DR OrthoDB; 999249at2759; -.
DR TreeFam; TF105320; -.
DR Reactome; R-RNO-2142696; Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
DR Reactome; R-RNO-2142700; Synthesis of Lipoxins (LX).
DR Reactome; R-RNO-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-RNO-9018677; Biosynthesis of DHA-derived SPMs.
DR Reactome; R-RNO-9025106; Biosynthesis of DPAn-6 SPMs.
DR Reactome; R-RNO-9026290; Biosynthesis of DPAn-3-derived maresins.
DR UniPathway; UPA00881; -.
DR PRO; PR:F1LQ70; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000027037; Expressed in esophagus and 18 other cell types or tissues.
DR ExpressionAtlas; F1LQ70; baseline and differential.
DR Genevisible; F1LQ70; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; ISS:UniProtKB.
DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; ISS:UniProtKB.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; ISS:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0071396; P:cellular response to lipid; IEP:RGD.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; IDA: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; IMP:RGD.
DR GO; GO:0010656; P:negative regulation of muscle cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:RGD.
DR GO; GO:1905956; P:positive regulation of endothelial tube morphogenesis; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; IMP:RGD.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0033559; P:unsaturated fatty acid metabolic process; ISO:RGD.
DR Gene3D; 3.10.450.60; -; 1.
DR Gene3D; 2.60.60.20; PLAT/LH2 domain; 1.
DR InterPro; IPR000907; LipOase.
DR InterPro; IPR013819; LipOase_C.
DR InterPro; IPR036226; LipOase_C_sf.
DR InterPro; IPR020834; LipOase_CS.
DR InterPro; IPR020833; LipOase_Fe_BS.
DR InterPro; IPR001885; LipOase_mml.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR PANTHER; PTHR11771; LIPOXYGENASE; 1.
DR PANTHER; PTHR11771:SF4; POLYUNSATURATED FATTY ACID LIPOXYGENASE ALOX12; 1.
DR Pfam; PF00305; Lipoxygenase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PRINTS; PR00087; LIPOXYGENASE.
DR PRINTS; PR00467; MAMLPOXGNASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF49723; Lipase/lipooxygenase domain (PLAT/LH2 domain); 1.
DR SUPFAM; SSF48484; Lipoxigenase; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
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_0000423852"
FT DOMAIN 2..114
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 114..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:0007744|PubMed:22673903"
SQ SEQUENCE 663 AA; 75534 MW; 2DC11842CDA025CA CRC64;
MGRYRVRVVT GAWLFSGSVN LVRLWLVGAH REARLELQLR PARGKEEEFD FDVAEDLGPL
QFVKLHKEHT VVDDAWFCNL ITVQGPGMSA EAVFPCYRWV QGEGILRLPE GTARLAGDNA
LDVFQKHREK ELKERQQTYR WATWKQGLPQ TIAADCKDDL PPNMRFHEEK RLDFEWTLKA
GVLEMGLKRV YTLLRSWNRL EDFDQIFWGQ KSALAEKVHR CWQEDELFGY QFLNGANPML
LRRSTSLPSR LVLPPGTEEL QAQLEKELKD GCLFEADFIL LDGIPANVIR GEQQYLAAPL
VMLRMDPSGK LLPMAIQIQP PNPSSPAPTL FLPSDPPLAW LLAKIWVRNS DFQLQELQFH
LLNTHLVAEV IAVATMRCLP GLHPIFKLLV PHIRYTMEIN TRSRTQLISD GGIFDQVVST
GGGGHVQLLT RAVAQLTYCS LCPPDDLATR GLLRVPSALY AQDALQLWEV TARYVNGMVH
LFYQSDDIVR GDPELQAWCR EITEVGLCHA QDRGFPVSFQ SRAQLCHFLT MCVFTCTSQH
AAINQGQLDW YGWVPNAPCT MRMPPPTSKD DVTMETIMGS LPDVQKSCLQ MTITWHLGRL
QPDMVPLGHH KEKYFSDPRT KAVLSQFQAD LENLEKEITA RNQQLDLPYE YLKPSRIENS
ITI
//
