LX12E_MOUSE
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 03-AUG-2022, entry version 159.
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:8798535, PubMed:9037187,
CC PubMed:11256953). 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;
CC Evidence={ECO:0000255|PROSITE-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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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_145684.1.
DR AlphaFoldDB; P55249; -.
DR SMR; P55249; -.
DR STRING; 10090.ENSMUSP00000019051; -.
DR SwissLipids; SLP:000000685; -.
DR iPTMnet; P55249; -.
DR PhosphoSitePlus; P55249; -.
DR PaxDb; P55249; -.
DR PeptideAtlas; P55249; -.
DR PRIDE; P55249; -.
DR ProteomicsDB; 292055; -.
DR DNASU; 11685; -.
DR Ensembl; ENSMUST00000019051; ENSMUSP00000019051; ENSMUSG00000018907.
DR GeneID; 11685; -.
DR KEGG; mmu:11685; -.
DR UCSC; uc007jun.1; mouse.
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; ARMQKTF; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; P55249; -.
DR TreeFam; TF105320; -.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 11685; 6 hits in 74 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 tissues.
DR ExpressionAtlas; P55249; baseline and differential.
DR Genevisible; P55249; MM.
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: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; IMP:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; IBA:GO_Central.
DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:0019372; P:lipoxygenase pathway; IMP:UniProtKB.
DR CDD; cd01753; PLAT_LOX; 1.
DR InterPro; IPR000907; LipOase.
DR InterPro; IPR013819; LipOase_C.
DR InterPro; IPR036226; LipOase_C_sf.
DR InterPro; IPR020834; LipOase_CS.
DR InterPro; IPR020833; LipOase_Fe_BS.
DR InterPro; IPR001885; LipOase_mml.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR042062; PLAT_LOX_verte.
DR PANTHER; PTHR11771; PTHR11771; 1.
DR Pfam; PF00305; Lipoxygenase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PRINTS; PR00087; LIPOXYGENASE.
DR PRINTS; PR00467; MAMLPOXGNASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF48484; SSF48484; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW 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
