ID   LX12E_MOUSE             Reviewed;         662 AA.
AC   P55249; Q91YW6;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   02-SEP-2026, entry version 177.
DE   RecName: Full=Polyunsaturated fatty acid (12S)/(13S)-lipoxygenase, epidermal-type {ECO:0000305};
DE            EC=1.13.11.- {ECO:0000269|PubMed:11256953};
DE   AltName: Full=Arachidonate (12S)-lipoxygenase, epidermal-type {ECO:0000305};
DE            Short=12-LOX-e {ECO:0000250|UniProtKB:D3ZQF9};
DE            Short=e(12S)-LOX {ECO:0000303|PubMed:11256953};
DE            EC=1.13.11.31 {ECO:0000269|PubMed:11256953, ECO:0000269|PubMed:8798535};
DE   AltName: Full=Linoleate (13S)-lipoxygenase {ECO:0000305};
GN   Name=Alox12e {ECO:0000312|MGI:MGI:1274790};
GN   Synonyms=Alox12-ps2, Aloxe {ECO:0000303|PubMed:9037187};
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], FUNCTION, TISSUE SPECIFICITY, AND CATALYTIC
RP   ACTIVITY.
RC   STRAIN=C57BL/6 X 129/Sv; TISSUE=Epidermis;
RX   PubMed=8798535; DOI=10.1074/jbc.271.38.23338;
RA   Funk C.D., Keeney D.S., Oliw E.H., Boeglin W.E., Brash A.R.;
RT   "Functional expression and cellular localization of a mouse epidermal
RT   lipoxygenase.";
RL   J. Biol. Chem. 271:23338-23344(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=129/Sv; TISSUE=Epidermis;
RX   PubMed=7492614; DOI=10.1016/0005-2760(95)00158-9;
RA   van Dijk K.W., Steketee K., Havekes L., Frants R., Hofker M.;
RT   "Genomic and cDNA cloning of a novel mouse lipoxygenase gene.";
RL   Biochim. Biophys. Acta 1259:4-8(1995).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=NMRI; TISSUE=Skin;
RX   PubMed=9037187; DOI=10.1016/s0014-5793(96)01517-7;
RA   Kinzig A., Fuerstenberger G., Mueller F., Vogel S., Mueller-Decker K.,
RA   Mincheva A., Lichter P., Marks F., Krieg P.;
RT   "Murine epidermal lipoxygenase (Aloxe) encodes a 12-lipoxygenase isoform.";
RL   FEBS Lett. 402:162-166(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-260; LEU-453 AND
RP   SER-617.
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
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   [5]
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).
CC   -!- FUNCTION: Catalyzes the regio and stereo-specific incorporation of a
CC       single molecule of dioxygen into free and esterified polyunsaturated
CC       fatty acids generating lipid hydroperoxides that can be further reduced
CC       to the corresponding hydroxy species (PubMed:11256953, PubMed:8798535,
CC       PubMed:9037187). Shows increasing catalytic activity within the series
CC       arachidonic acid < 5,8,11-eicosatrienoic acid < linoleic acid <
CC       8,11,14-eicosatrienoic acid (PubMed:11256953).
CC       {ECO:0000269|PubMed:11256953, ECO:0000269|PubMed:8798535,
CC       ECO:0000269|PubMed:9037187}.
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:8798535, ECO:0000269|PubMed:9037187};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC         Evidence={ECO:0000305|PubMed:11256953, ECO:0000305|PubMed:8798535};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=1-O-methyl-(9Z,12Z)-octadecadienoate + O2 = 1-O-methyl-(13S)-
CC         hydroperoxy-(9Z,11E)-octadecadienoate; Xref=Rhea:RHEA:41756,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:69080, ChEBI:CHEBI:78040;
CC         Evidence={ECO:0000269|PubMed:11256953};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41757;
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=(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=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-
CC         methyl-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate;
CC         Xref=Rhea:RHEA:41315, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC         ChEBI:CHEBI:78035; Evidence={ECO:0000269|PubMed:11256953};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41316;
CC         Evidence={ECO:0000305|PubMed:11256953};
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         Evidence={ECO:0000269|PubMed:11256953};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22781;
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   -!- COFACTOR:
CC       Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU00726};
CC       Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE-
CC       ProRule:PRU00726};
CC   -!- ACTIVITY REGULATION: Arachidonate 12-lipoxygenase activity is decreased
CC       when the pH decreases from 7.4 to 6.0. {ECO:0000269|PubMed:11256953}.
CC   -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC       biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00726}.
CC   -!- TISSUE SPECIFICITY: Expressed in epidermis.
CC       {ECO:0000269|PubMed:8798535}.
CC   -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
CC   -!- CAUTION: Was originally thought to be an arachidonate 8-lipoxygenase
CC       and was called LOX8. {ECO:0000305}.
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DR   EMBL; U39200; AAC52869.1; -; mRNA.
DR   EMBL; U24181; AAC52324.1; -; Genomic_DNA.
DR   EMBL; X99252; CAA67625.1; -; mRNA.
DR   EMBL; BC013751; AAH13751.1; -; mRNA.
DR   EMBL; BC051047; AAH51047.1; -; mRNA.
DR   CCDS; CCDS24943.1; -.
DR   RefSeq; NP_663717.1; NM_145684.2.
DR   AlphaFoldDB; P55249; -.
DR   SMR; P55249; -.
DR   FunCoup; P55249; 119.
DR   STRING; 10090.ENSMUSP00000019051; -.
DR   SwissLipids; SLP:000000685; -.
DR   iPTMnet; P55249; -.
DR   PhosphoSitePlus; P55249; -.
DR   PaxDb; 10090-ENSMUSP00000019051; -.
DR   PeptideAtlas; P55249; -.
DR   ProteomicsDB; 292055; -.
DR   DNASU; 11685; -.
DR   Ensembl; ENSMUST00000019051.3; ENSMUSP00000019051.3; ENSMUSG00000018907.11.
DR   GeneID; 11685; -.
DR   KEGG; mmu:11685; -.
DR   UCSC; uc007jun.1; mouse.
DR   AGR; MGI:1274790; -.
DR   CTD; 11685; -.
DR   MGI; MGI:1274790; Alox12e.
DR   VEuPathDB; HostDB:ENSMUSG00000018907; -.
DR   eggNOG; ENOG502QQSP; Eukaryota.
DR   GeneTree; ENSGT00940000163215; -.
DR   HOGENOM; CLU_004282_3_3_1; -.
DR   InParanoid; P55249; -.
DR   OMA; QKTFTKF; -.
DR   OrthoDB; 407298at2759; -.
DR   PhylomeDB; P55249; -.
DR   BRENDA; 1.13.11.31; 3474.
DR   UniPathway; UPA00881; -.
DR   BioGRID-ORCS; 11685; 6 hits in 79 CRISPR screens.
DR   PRO; PR:P55249; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P55249; protein.
DR   Bgee; ENSMUSG00000018907; Expressed in skin of external ear and 44 other cell types or tissues.
DR   ExpressionAtlas; P55249; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IMP:UniProtKB.
DR   GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IBA:GO_Central.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; IMP:UniProtKB.
DR   GO; GO:0019369; P:arachidonate metabolic process; IMP:UniProtKB.
DR   GO; GO:0034440; P:lipid oxidation; IEA:InterPro.
DR   GO; GO:0019372; P:lipoxygenase pathway; IMP:UniProtKB.
DR   CDD; cd01753; PLAT_LOX; 1.
DR   FunFam; 3.10.450.60:FF:000004; Arachidonate 12-lipoxygenase, 12S-type; 1.
DR   FunFam; 1.20.245.10:FF:000001; Arachidonate 5-lipoxygenase a; 1.
DR   Gene3D; 3.10.450.60; -; 1.
DR   Gene3D; 1.20.245.10; Lipoxygenase-1, Domain 5; 1.
DR   Gene3D; 2.60.60.20; PLAT/LH2 domain; 1.
DR   InterPro; IPR000907; LipOase.
DR   InterPro; IPR013819; LipOase_C.
DR   InterPro; IPR036226; LipOase_C_sf.
DR   InterPro; IPR020834; LipOase_CS.
DR   InterPro; IPR020833; LipOase_Fe_BS.
DR   InterPro; IPR001885; LipOase_mml.
DR   InterPro; IPR001024; PLAT/LH2_dom.
DR   InterPro; IPR036392; PLAT/LH2_dom_sf.
DR   InterPro; IPR042062; PLAT_LOX_verte.
DR   PANTHER; PTHR11771; LIPOXYGENASE; 1.
DR   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; Iron; Lipid metabolism;
KW   Metal-binding; Oxidoreductase; Reference proteome.
FT   CHAIN           1..662
FT                   /note="Polyunsaturated fatty acid (12S)/(13S)-lipoxygenase,
FT                   epidermal-type"
FT                   /id="PRO_0000220688"
FT   DOMAIN          2..114
FT                   /note="PLAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT   DOMAIN          115..662
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         662
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   VARIANT         260
FT                   /note="V -> L (in strain: FVB/N)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT   VARIANT         453
FT                   /note="V -> L (in strain: FVB/N)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT   VARIANT         617
FT                   /note="P -> S (in strain: FVB/N)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT   CONFLICT        619
FT                   /note="P -> A (in Ref. 2; AAC52324)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   662 AA;  75456 MW;  D67768415EE988F7 CRC64;
     MVKYKILVAT GDSVFAGSAN LVHLWLVGEH GEADLGKQLR PLLGRKTELE VDVPLHLGRL
     LAVKLRKQKG LLDSDWFCKS ITVQGPGTQG EAFFPCYSWV QGKETICLTE GTALKVTDDT
     QNLFRKYREQ ELENRRNVYR WGSWKEGLIL PIAGSTERDL PRNQRFMKDK DLDFSLSLVK
     ELKNFAIKGT LDFVSRVQKL EDYQKVFPHT KTALPERVRG SWKEDALFGY QFLNGANPML
     LRRSMRLPAR LVLPPGMEDV QTQLEKELKA GSLFEVDFSL LDGVKPNIII FKQQYVTAPL
     VMLKLQPDGR LLPMVIQLQP PRHGCPPPLL FLPSDPPMAW LLAKIWVRSS DFQLHQLQSH
     LLRGHLMAEV ISVATMRSLP SLHPIYKLLA PHFRYTMEIN TLARNNLVSE WGIFDLVVST
     GSGGHVDILQ RATSCLTYRS FCPPDDLADR GLVGVKSSLY AQDALRLWEI ISRYVERMVE
     LFYRSDTDVK EDPELQVWCR EVTEVGLLGA QDRGFPLSLE SRAELCRFVA MCIFTCTGQH
     ASTHLGQLDW YAWIPNGPCT MRKPPPISKD VTERDIVDSL PCLQQARMQI TVTKFLGRRQ
     PVMVALGQHK EEYFSGPRPR DVLKQFQEEL AIMDKEIEVR NASLDLPYEY LRPSLVENSV
     TI
//