LX12B_RAT
ID LX12B_RAT Reviewed; 701 AA.
AC Q2KMM4; Q2KMM5;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Arachidonate 12-lipoxygenase, 12R-type {ECO:0000305};
DE Short=12R-LOX;
DE Short=12R-lipoxygenase;
DE EC=1.13.11.- {ECO:0000269|PubMed:23382512};
DE AltName: Full=Epidermis-type lipoxygenase 12;
GN Name=Alox12b {ECO:0000312|RGD:1305330};
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] {ECO:0000312|EMBL:AAX85363.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Brown Norway/Cub, SHR/OlaIpcv {ECO:0000312|EMBL:AAX85363.1}, and
RC Wistar Hd; TISSUE=Testis {ECO:0000312|EMBL:AAX85363.1};
RX PubMed=15222128;
RA Liska F., Goesele C., Kren V., Huebner N., Krenova D.;
RT "Molecular analysis of the sex hormone-binding globulin gene in the rat
RT hypodactylous mutation (Hd).";
RL Folia Biol. (Praha) 50:63-68(2004).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
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). In the skin,
CC acts upstream of ALOXE3 on the lineolate moiety of esterified omega-
CC hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone
CC derivative, a crucial step in the conjugation of omega-hydroxyceramide
CC to membrane proteins. Therefore plays a crucial role in the synthesis
CC of corneocytes lipid envelope and the establishment of the skin barrier
CC to water loss. May also play a role in the regulation of the expression
CC of airway mucins (By similarity). {ECO:0000250|UniProtKB:O75342,
CC ECO:0000269|PubMed:23382512}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12R)-hydroperoxy-
CC (5Z,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:41336,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75230;
CC Evidence={ECO:0000269|PubMed:23382512};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41337;
CC Evidence={ECO:0000305|PubMed:23382512};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-[omega-(9Z,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-
CC (1<->1)-octadecasphing-4E-enine + O2 = N-[omega-(9R)-hydroperoxy-
CC (10E,12Z)-octadecadienoyloxy]acyl-beta-D-glucosyl-(1<->1)-
CC octadecasphing-4E-enine; Xref=Rhea:RHEA:40495, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:134621, ChEBI:CHEBI:134624;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40496;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-acyl (9Z,12Z)-octadecadienoate octadecasphin-4E-enine + O2 =
CC N-acyl (9R)-hydroperoxy-(10E,12Z)-octadecadienoate octadecasphing-4E-
CC enine; Xref=Rhea:RHEA:41239, ChEBI:CHEBI:15379, ChEBI:CHEBI:77888,
CC ChEBI:CHEBI:77889; Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41240;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z,9Z,12Z)-octadecatrienoate + O2 = 10-hydroperoxy-
CC (6Z,8E,12Z)-octadecatrienoate; Xref=Rhea:RHEA:43476,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32391, ChEBI:CHEBI:83342;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43477;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = 14-
CC hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:43472, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:83336; Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43473;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = (8Z,10E,14Z)-12-
CC hydroperoxyeicosatrienoate; Xref=Rhea:RHEA:43468, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:71589, ChEBI:CHEBI:83334;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43469;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 =
CC (5Z,7Z,8Z,10E,14Z,17Z)-12-hydroperoxyeicosapentaenoate;
CC Xref=Rhea:RHEA:41344, ChEBI:CHEBI:15379, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:78078; Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41345;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6Z,9Z,12Z)-octadecatrienoate + O2 = 10R-hydroperoxy-
CC (6Z,8E,12Z)-octadecatrienoate; Xref=Rhea:RHEA:41340,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32391, ChEBI:CHEBI:78070;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41341;
CC Evidence={ECO:0000250|UniProtKB:O75342};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-methyl
CC (5Z,8Z,10E,12R,14Z)-hydroperoxyiecosatetraenoate;
CC Xref=Rhea:RHEA:41311, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC ChEBI:CHEBI:78034; Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41312;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-
CC methyl-8-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate;
CC Xref=Rhea:RHEA:43480, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC ChEBI:CHEBI:83344; Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43481;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 1-O-
CC methyl-(8R)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:61868, ChEBI:CHEBI:15379, ChEBI:CHEBI:78033,
CC ChEBI:CHEBI:78180; Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61869;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-(9Z,12Z)-octadecadienoate + O2 = 1-O-methyl-(9R)-
CC hydroperoxy-(10E,12Z)-octadecadienoate; Xref=Rhea:RHEA:61872,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:69080, ChEBI:CHEBI:145036;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61873;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC 1-O-methyl-8-hydroperoxy-20-hydroxy-(5Z,9E,11Z,14Z)-
CC eicosatetraenoate; Xref=Rhea:RHEA:61876, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145032, ChEBI:CHEBI:145033;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61877;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC 1-O-methyl-12-hydroperoxy-20-hydroxy-(5Z,8Z,10E,14Z)-
CC eicosatetraenoate; Xref=Rhea:RHEA:61880, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145032, ChEBI:CHEBI:145034;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61881;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-methyl-20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC 1-O-methyl-9-hydroperoxy-20-hydroxy-(5Z,7E,11Z,14Z)-
CC eicosatetraenoate; Xref=Rhea:RHEA:61884, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:145032, ChEBI:CHEBI:145035;
CC Evidence={ECO:0000250|UniProtKB:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61885;
CC Evidence={ECO:0000250|UniProtKB:O70582};
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:O70582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41757;
CC Evidence={ECO:0000250|UniProtKB:O70582};
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: Increased by calcium.
CC {ECO:0000250|UniProtKB:O70582}.
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis.
CC -!- PATHWAY: Lipid metabolism; sphingolipid metabolism.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00726}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:O75342}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000255}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=about water - Issue 153 of
CC September 2013;
CC URL="https://web.expasy.org/spotlight/back_issues/153/";
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DR EMBL; AY903231; AAX85361.1; -; mRNA.
DR EMBL; AY903232; AAX85362.1; -; mRNA.
DR EMBL; AY903233; AAX85363.1; -; mRNA.
DR RefSeq; NP_001034466.1; NM_001039377.1.
DR AlphaFoldDB; Q2KMM4; -.
DR SMR; Q2KMM4; -.
DR STRING; 10116.ENSRNOP00000033009; -.
DR PaxDb; Q2KMM4; -.
DR GeneID; 287425; -.
DR KEGG; rno:287425; -.
DR UCSC; RGD:1305330; rat.
DR CTD; 242; -.
DR RGD; 1305330; Alox12b.
DR eggNOG; ENOG502SJSP; Eukaryota.
DR InParanoid; Q2KMM4; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; Q2KMM4; -.
DR Reactome; R-RNO-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR UniPathway; UPA00222; -.
DR UniPathway; UPA00881; -.
DR PRO; PR:Q2KMM4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0106237; F:arachidonate 12(R)-lipoxygenase activity; IEA:RHEA.
DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; ISS:UniProtKB.
DR GO; GO:0047677; F:arachidonate 8(R)-lipoxygenase activity; ISO:RGD.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:1990136; F:linoleate 9S-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; ISO:RGD.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:0019372; P:lipoxygenase pathway; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0070257; P:positive regulation of mucus secretion; ISS:UniProtKB.
DR GO; GO:0006497; P:protein lipidation; ISS:UniProtKB.
DR GO; GO:0006665; P:sphingolipid metabolic process; ISS: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..701
FT /note="Arachidonate 12-lipoxygenase, 12R-type"
FT /id="PRO_0000244486"
FT DOMAIN 2..119
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 120..701
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 398
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 403
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 578
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 582
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 701
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT CONFLICT 276
FT /note="H -> L (in Ref. 1; AAX85362)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 701 AA; 80741 MW; 6BE209D98DEB4DB9 CRC64;
MATYKVKVAT GTDFFSGTLD SISLTIVGTQ GESHKQRLNH FGRDFATGAV DDYTVQCQQD
LGELIIIRLH KEPHSFLPKD PWYCNYVQIC APNCRVYHFP AYQWMDGYET LSLREATGKT
TADDTLPILL EHRQEEIRAK KDFYHWRVFV PGLPNYVDIP SYHPPPRRCR NPNRPEWNGY
IPGFPILINI KATRFLNLNL RFSFVKTASF FYRLGPMALA FKLRGLVDRK RSWKRLKDIK
NIFPATKTVV SEYVAEHWTE DSFFGYQYLN GINPGHIRRC MQIPDKFPVT DEMVAPFLGE
GTCLQAELEK GNIYLADYRI LDGIPTVELN GQKQHHCAPI CLLHFGPDGN MMPIAIQLSQ
TPGPDCPIFL PNDSEWDWLL AKTWVRYAEF YSHEAVAHLL ESHLIGEAFC LALLRNLPMC
HPLYKLLIPH TRYNVQINSI GRALLLNKGG LSARAMSLGL EGFAQVMVRG LSELTYKSLC
IPNDFVERGV QDLPGYYFRD DSLAVWYAME RYVTEIITYY YPNDAAVEGD PELQCWVQEI
FKECLLERES SGFPTCLRTV PELIEYVTMV MYTCSARHAA VNTGQLEYTS WMPNFPSSMR
NPPMQSKGLT TLQTFMDTLP DVKTTCIVLL VLWTLCREPD DRRPLGHFPD IHFVEEAPRR
SMEAFRQNLN QISHNIRQRN KCLNLPYYYL DPVLIENSIS I
