LX12E_RAT
ID LX12E_RAT Reviewed; 662 AA.
AC D3ZQF9;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Polyunsaturated fatty acid (12S)/(13S)-lipoxygenase, epidermal-type {ECO:0000305};
DE EC=1.13.11.- {ECO:0000250|UniProtKB:P55249};
DE AltName: Full=Arachidonate (12S)-lipoxygenase, epidermal-type;
DE Short=12-LOX-e {ECO:0000303|PubMed:23382512};
DE Short=e(12S)-LOX {ECO:0000250|UniProtKB:P55249};
DE EC=1.13.11.31 {ECO:0000269|PubMed:23382512};
DE AltName: Full=Linoleate (13S)-lipoxygenase {ECO:0000250|UniProtKB:P55249};
GN Name=Alox12e {ECO:0000312|RGD:1307642};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION.
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 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:23382512). Shows
CC increasing catalytic activity within the series arachidonic acid <
CC 5,8,11-eicosatrienoic acid < linoleic acid < 8,11,14-eicosatrienoic
CC acid (By similarity). {ECO:0000250|UniProtKB:P55249,
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:0000305|PubMed:23382512};
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:0000250|UniProtKB:P55249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41757;
CC Evidence={ECO:0000250|UniProtKB:P55249};
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:P55249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41329;
CC Evidence={ECO:0000250|UniProtKB:P55249};
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:P55249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41325;
CC Evidence={ECO:0000250|UniProtKB:P55249};
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:0000250|UniProtKB:P55249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41316;
CC Evidence={ECO:0000250|UniProtKB:P55249};
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:0000250|UniProtKB:P55249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22781;
CC Evidence={ECO:0000250|UniProtKB:P55249};
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:P55249};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333;
CC Evidence={ECO:0000250|UniProtKB:P55249};
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:0000250|UniProtKB:P55249}.
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00726}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
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DR EMBL; AABR06064408; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473948; EDM04999.1; -; Genomic_DNA.
DR RefSeq; NP_001100484.1; NM_001107014.1.
DR AlphaFoldDB; D3ZQF9; -.
DR SMR; D3ZQF9; -.
DR STRING; 10116.ENSRNOP00000025910; -.
DR PaxDb; D3ZQF9; -.
DR GeneID; 303252; -.
DR KEGG; rno:303252; -.
DR UCSC; RGD:1307642; rat.
DR CTD; 11685; -.
DR RGD; 1307642; Alox12e.
DR VEuPathDB; HostDB:ENSRNOG00000019074; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; D3ZQF9; -.
DR OMA; ARMQKTF; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; D3ZQF9; -.
DR TreeFam; TF105320; -.
DR UniPathway; UPA00881; -.
DR PRO; PR:D3ZQF9; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Proteomes; UP000234681; Chromosome 10.
DR Bgee; ENSRNOG00000019074; Expressed in thymus and 6 other tissues.
DR Genevisible; D3ZQF9; RN.
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; ISS: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; ISS: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: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; 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 3: Inferred from homology;
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_0000423431"
FT DOMAIN 2..114
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 114..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 544
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"
SQ SEQUENCE 662 AA; 75466 MW; 958F95224C29A218 CRC64;
MGKYKILVVT GDSLLAGSTN LVQLWLVGEH AEADLGKQLR PLRGRKTELE IDVPLHLGRL
LVVKLRKHKG LLDSDWFCKW ITVQGPGIQG EAFFPCYSWV QGKETIYLPE GTALKVNDDT
KNLFRKYREQ ELEDRRNVYR WGSWKEGLIL PIAGSTERDL PRNQRFMEDK DLDFSLSLAK
VLKDFAIKGT LDFVSRVQHL EDYQKVFPHS KTALAGRVRD SWKEDALFGY QFLNGANPML
LRRSKRLPAR LVLPPGMEDL QTQLEKELKA GSLFEADFSL LDGVKPNVII FKQQHVAAPL
VMLKLQSDGR LLPMVIQLQP PRHGCPPPLL FLPSDPPMAW LLAKIWVRSS DFQVHQLQSH
LLRGHLMAEV ISVATMRSLP SLHPIYKLLA PHFRYTMEIN TLARNNLVSE WGIFDLVVST
GSGGHVDILQ RATACLTYRS FCPPDDLADR GLLDVKSSLY ARDALRLWEI ISRYVGRMVE
LFYKNDREVK EDPELQVWCR EVTEIGLLGA QDRGFPLSLE SRAQLCRFVT MCIFTCTGQH
ASTHLGQLDW YSWIPNGPCT MRKPPPTSKN VTEGDILDAL PCLQQARMQI TFTKFLGRHQ
PVMVALGQHK EEYFSDPGAR AVLKQFQEEL AVMDKEIEVR NASLDLPYEY LRPSMVENSV
TI
