GENTAUR Molecular Products.

 LOX15_RABIT             Reviewed;         663 AA.
 P12530; O19043;
 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
 23-JAN-2007, sequence version 3.
 15-FEB-2017, entry version 139.
 RecName: Full=Arachidonate 15-lipoxygenase;
          Short=15-LOX;
          EC=1.13.11.33 {ECO:0000269|PubMed:9414270, ECO:0000269|PubMed:9600854};
 AltName: Full=12/15-lipoxygenase;
 AltName: Full=Arachidonate 12-lipoxygenase, leukocyte-type;
          Short=12-LOX;
          Short=L-12LO;
          EC=1.13.11.31 {ECO:0000269|PubMed:9600854};
 AltName: Full=Arachidonate omega-6 lipoxygenase;
 AltName: Full=Erythroid cell-specific 15-lipoxygenase;
 Name=ALOX15;
 Oryctolagus cuniculus (Rabbit).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
 Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae;
 Oryctolagus.
 NCBI_TaxID=9986;
 [1]
 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
 PubMed=2612916; DOI=10.1016/0378-1119(89)90526-X;
 O'Prey J., Chester J., Thiele B.J., Janetzki S., Prehn S., Fleming J.,
 Harrison P.R.;
 "The promoter structure and complete sequence of the gene encoding the
 rabbit erythroid cell-specific 15-lipoxygenase.";
 Gene 84:493-499(1989).
 [2]
 NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
 MUTAGENESIS OF PHE-353.
 PubMed=9600854; DOI=10.1006/jmbi.1998.1737;
 Berger M., Schwarz K., Thiele H., Reimann I., Huth A., Borngraeber S.,
 Kuehn H., Thiele B.-J.;
 "Simultaneous expression of leukocyte-type 12-lipoxygenase and
 reticulocyte-type 15-lipoxygenase in rabbits.";
 J. Mol. Biol. 278:935-948(1998).
 [3]
 NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-31.
 PubMed=2777088; DOI=10.1016/0378-1119(89)90103-0;
 Fleming J., Thiele B.J., Chester J., O'Prey J., Janetzki S.,
 Aitken A., Anton I.A., Rapoport S.M., Harrison P.R.;
 "The complete sequence of the rabbit erythroid cell-specific 15-
 lipoxygenase mRNA: comparison of the predicted amino acid sequence of
 the erythrocyte lipoxygenase with other lipoxygenases.";
 Gene 79:181-188(1989).
 [4]
 NUCLEOTIDE SEQUENCE [MRNA] OF 1-31.
 PubMed=3123326; DOI=10.1016/0378-1119(87)90182-X;
 Thiele B.J., Fleming J., Kasturi K., O'Prey J., Black E., Chester J.,
 Rapoport S.M., Harrison P.R.;
 "Cloning of a rabbit erythroid-cell-specific lipoxygenase mRNA.";
 Gene 57:111-119(1987).
 [5]
 NUCLEOTIDE SEQUENCE [MRNA], AND GENE STRUCTURE.
 PubMed=2386503;
 Thiele B.J., Fleming J., Chester J., O'Prey J., Prehn S., Janetzki S.,
 Rapoport S.M., Harrison P.R.;
 "Structure of the mRNA and of the gene coding for the rabbit erythroid
 15-lipoxygenase.";
 Biomed. Biochim. Acta 49:S17-S24(1990).
 [6]
 CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
 SPECIFICITY.
 PubMed=9414270;
 Brinckmann R., Schnurr K., Heydeck D., Rosenbach T., Kolde G.,
 Kuehn H.;
 "Membrane translocation of 15-lipoxygenase in hematopoietic cells is
 calcium-dependent and activates the oxygenase activity of the
 enzyme.";
 Blood 91:64-74(1998).
 [7]
 X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH IRON AND
 SUBSTRATE ANALOG.
 PubMed=9406550; DOI=10.1038/nsb1297-1003;
 Gillmor S.A., Villasenor A., Fletterick R., Sigal E., Browner M.F.;
 "The structure of mammalian 15-lipoxygenase reveals similarity to the
 lipases and the determinants of substrate specificity.";
 Nat. Struct. Biol. 4:1003-1009(1997).
 -!- FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the
     stereo-specific peroxidation of free and esterified
     polyunsaturated fatty acids generating a spectrum of bioactive
     lipid mediators. Converts arachidonic acid into 12-
     hydroperoxyeicosatetraenoic acid/12-HPETE and 15-
     hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic
     acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)-
     hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin
     A3. Probably plays an important role in the immune and
     inflammatory responses. Through the oxygenation of membrane-bound
     phosphatidylethanolamine in macrophages may favor clearance of
     apoptotic cells during inflammation by resident macrophages and
     prevent an autoimmune response associated with the clearance of
     apoptotic cells by inflammatory monocytes. In parallel, may
     regulate actin polymerization which is crucial for several
     biological processes, including macrophage function. May also
     regulate macrophage function through regulation of the peroxisome
     proliferator activated receptor signaling pathway. Finally, it is
     also involved in the cellular response to IL13/interleukin-13. In
     addition to its role in the immune and inflammatory responses, may
     play a role in epithelial wound healing in the cornea maybe
     through production of lipoxin A4. May also play a role in
     endoplasmic reticulum stress response and the regulation of bone
     mass. {ECO:0000269|PubMed:9414270, ECO:0000269|PubMed:9600854}.
 -!- CATALYTIC ACTIVITY: Arachidonate + O(2) = (5Z,8Z,10E,14Z)-(12S)-
     12-hydroperoxyicosa-5,8,10,14-tetraenoate.
     {ECO:0000269|PubMed:9600854}.
 -!- CATALYTIC ACTIVITY: Arachidonate + O(2) = (5Z,8Z,11Z,13E)-(15S)-
     15-hydroperoxyicosa-5,8,11,13-tetraenoate.
     {ECO:0000269|PubMed:9414270, ECO:0000269|PubMed:9600854}.
 -!- COFACTOR:
     Name=Fe cation; Xref=ChEBI:CHEBI:24875;
     Note=Binds 1 Fe cation per subunit.;
 -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
     biosynthesis. {ECO:0000269|PubMed:9600854}.
 -!- SUBUNIT: Interacts with PEBP1; in response to IL13/interleukin-13,
     prevents the interaction of PEBP1 with RAF1 to activate the ERK
     signaling cascade. {ECO:0000250}.
 -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
     {ECO:0000269|PubMed:9414270}. Cell membrane
     {ECO:0000269|PubMed:9414270}; Peripheral membrane protein
     {ECO:0000269|PubMed:9414270}. Lipid droplet {ECO:0000250}.
     Note=Translocates from the cytosol to the plasma membrane when
     stimulated by IL13/interleukin-13 and in macrophages binding
     apoptotic cells (By similarity). Predominantly cytosolic; becomes
     enriched at membranes upon calcium binding. {ECO:0000250}.
 -!- TISSUE SPECIFICITY: Detected in reticulocytes (at protein level).
     {ECO:0000269|PubMed:9414270}.
 -!- DOMAIN: The PLAT domain can bind calcium ions; this promotes
     association with membranes. {ECO:0000250}.
 -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
 -!- CAUTION: According to the authors the mRNA described in
     PubMed:9600854 may be encoded by a gene different from ALOX15.
     {ECO:0000305}.
 -----------------------------------------------------------------------
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 EMBL; M33291; AAA75014.1; -; Genomic_DNA.
 EMBL; Z97654; CAB10746.1; -; mRNA.
 EMBL; M27214; AAB86978.1; -; mRNA.
 EMBL; M22617; AAA31385.1; -; mRNA.
 PIR; JQ0018; JQ0018.
 RefSeq; NP_001075751.1; NM_001082282.1.
 RefSeq; NP_001139620.1; NM_001146148.1.
 UniGene; Ocu.2185; -.
 UniGene; Ocu.7470; -.
 PDB; 1LOX; X-ray; 2.40 A; A=2-663.
 PDB; 2P0M; X-ray; 2.40 A; A/B=2-663.
 PDBsum; 1LOX; -.
 PDBsum; 2P0M; -.
 ProteinModelPortal; P12530; -.
 SMR; P12530; -.
 STRING; 9986.ENSOCUP00000017072; -.
 BindingDB; P12530; -.
 ChEMBL; CHEMBL4358; -.
 SwissLipids; SLP:000001603; -.
 GeneID; 100009114; -.
 GeneID; 100271999; -.
 KEGG; ocu:100009114; -.
 KEGG; ocu:100271999; -.
 CTD; 239; -.
 CTD; 246; -.
 eggNOG; ENOG410IKAN; Eukaryota.
 eggNOG; ENOG410YN4N; LUCA.
 HOGENOM; HOG000234358; -.
 HOVERGEN; HBG005150; -.
 InParanoid; P12530; -.
 KO; K00460; -.
 BRENDA; 1.13.11.33; 1749.
 UniPathway; UPA00881; -.
 EvolutionaryTrace; P12530; -.
 PRO; PR:P12530; -.
 Proteomes; UP000001811; Unplaced.
 GO; GO:0005829; C:cytosol; ISS:UniProtKB.
 GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
 GO; GO:0005811; C:lipid particle; ISS:UniProtKB.
 GO; GO:0016020; C:membrane; ISS:UniProtKB.
 GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
 GO; GO:0004052; F:arachidonate 12-lipoxygenase activity; IDA:UniProtKB.
 GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; ISS:UniProtKB.
 GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
 GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
 GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
 GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
 GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
 GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
 GO; GO:0035963; P:cellular response to interleukin-13; ISS:UniProtKB.
 GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB.
 GO; GO:0043651; P:linoleic acid metabolic process; IDA:UniProtKB.
 GO; GO:2001303; P:lipoxin A4 biosynthetic process; ISS:UniProtKB.
 GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
 GO; GO:0002820; P:negative regulation of adaptive immune response; ISS:UniProtKB.
 GO; GO:0001503; P:ossification; ISS:UniProtKB.
 GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; ISS:UniProtKB.
 GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
 GO; GO:0010811; P:positive regulation of cell-substrate adhesion; ISS:UniProtKB.
 GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO; GO:1901074; P:regulation of engulfment of apoptotic cell; ISS:UniProtKB.
 GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
 GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
 GO; GO:0042060; P:wound healing; ISS:UniProtKB.
 Gene3D; 2.60.60.20; -; 1.
 InterPro; IPR000907; LipOase.
 InterPro; IPR013819; LipOase_C.
 InterPro; IPR020834; LipOase_CS.
 InterPro; IPR020833; LipOase_Fe_BS.
 InterPro; IPR001885; LipOase_mml.
 InterPro; IPR001024; PLAT/LH2_dom.
 PANTHER; PTHR11771; PTHR11771; 1.
 Pfam; PF00305; Lipoxygenase; 1.
 Pfam; PF01477; PLAT; 1.
 PRINTS; PR00087; LIPOXYGENASE.
 PRINTS; PR00467; MAMLPOXGNASE.
 SMART; SM00308; LH2; 1.
 SUPFAM; SSF48484; SSF48484; 1.
 SUPFAM; SSF49723; SSF49723; 1.
 PROSITE; PS00711; LIPOXYGENASE_1; 1.
 PROSITE; PS00081; LIPOXYGENASE_2; 1.
 PROSITE; PS51393; LIPOXYGENASE_3; 1.
 PROSITE; PS50095; PLAT; 1.
 1: Evidence at protein level;
 3D-structure; Calcium; Cell membrane; Complete proteome; Cytoplasm;
 Dioxygenase; Direct protein sequencing; Fatty acid metabolism; Iron;
 Lipid droplet; Lipid metabolism; Lipid-binding; Membrane;
 Metal-binding; Oxidoreductase; Reference proteome.
 INIT_MET      1      1       Removed. {ECO:0000269|PubMed:2777088}.
 CHAIN         2    663       Arachidonate 15-lipoxygenase.
                              /FTId=PRO_0000220699.
 DOMAIN        2    115       PLAT. {ECO:0000255|PROSITE-
                              ProRule:PRU00152}.
 DOMAIN      116    663       Lipoxygenase. {ECO:0000255|PROSITE-
                              ProRule:PRU00726}.
 METAL       361    361       Iron; catalytic. {ECO:0000255|PROSITE-
                              ProRule:PRU00726,
                              ECO:0000269|PubMed:9406550}.
 METAL       366    366       Iron; catalytic. {ECO:0000255|PROSITE-
                              ProRule:PRU00726,
                              ECO:0000269|PubMed:9406550}.
 METAL       541    541       Iron; catalytic. {ECO:0000255|PROSITE-
                              ProRule:PRU00726,
                              ECO:0000269|PubMed:9406550}.
 METAL       545    545       Iron; catalytic. {ECO:0000255|PROSITE-
                              ProRule:PRU00726,
                              ECO:0000269|PubMed:9406550}.
 METAL       663    663       Iron; via carboxylate; catalytic.
                              {ECO:0000255|PROSITE-ProRule:PRU00726,
                              ECO:0000269|PubMed:9406550}.
 MUTAGEN     353    353       F->L: Changes the stereoselectivity of
                              the oxygenation reaction to produce
                              (12S)-HPETE instead of (15S)-HPETE.
                              {ECO:0000269|PubMed:9600854}.
 CONFLICT     42     42       T -> S (in Ref. 2; CAB10746).
                              {ECO:0000305}.
 CONFLICT     64     64       R -> K (in Ref. 2; CAB10746).
                              {ECO:0000305}.
 CONFLICT    190    190       N -> D (in Ref. 3; AAB86978).
                              {ECO:0000305}.
 CONFLICT    194    194       I -> V (in Ref. 3; AAB86978).
                              {ECO:0000305}.
 CONFLICT    353    353       F -> L (in Ref. 2; CAB10746).
                              {ECO:0000305}.
 STRAND        3     10       {ECO:0000244|PDB:1LOX}.
 STRAND       12     15       {ECO:0000244|PDB:2P0M}.
 STRAND       19     30       {ECO:0000244|PDB:1LOX}.
 STRAND       32     39       {ECO:0000244|PDB:1LOX}.
 STRAND       46     52       {ECO:0000244|PDB:1LOX}.
 STRAND       59     68       {ECO:0000244|PDB:1LOX}.
 STRAND       70     72       {ECO:0000244|PDB:1LOX}.
 STRAND       76     88       {ECO:0000244|PDB:1LOX}.
 STRAND       93    101       {ECO:0000244|PDB:1LOX}.
 STRAND      103    105       {ECO:0000244|PDB:2P0M}.
 STRAND      107    110       {ECO:0000244|PDB:1LOX}.
 HELIX       126    139       {ECO:0000244|PDB:1LOX}.
 STRAND      152    154       {ECO:0000244|PDB:1LOX}.
 HELIX       158    160       {ECO:0000244|PDB:1LOX}.
 HELIX       163    165       {ECO:0000244|PDB:1LOX}.
 HELIX       169    175       {ECO:0000244|PDB:1LOX}.
 HELIX       189    192       {ECO:0000244|PDB:1LOX}.
 HELIX       193    195       {ECO:0000244|PDB:1LOX}.
 HELIX       201    206       {ECO:0000244|PDB:1LOX}.
 HELIX       214    222       {ECO:0000244|PDB:1LOX}.
 HELIX       226    235       {ECO:0000244|PDB:1LOX}.
 HELIX       259    270       {ECO:0000244|PDB:1LOX}.
 STRAND      274    278       {ECO:0000244|PDB:1LOX}.
 HELIX       280    282       {ECO:0000244|PDB:1LOX}.
 STRAND      301    306       {ECO:0000244|PDB:1LOX}.
 TURN        308    310       {ECO:0000244|PDB:2P0M}.
 STRAND      312    318       {ECO:0000244|PDB:1LOX}.
 HELIX       338    358       {ECO:0000244|PDB:1LOX}.
 HELIX       359    365       {ECO:0000244|PDB:1LOX}.
 HELIX       366    379       {ECO:0000244|PDB:1LOX}.
 HELIX       385    390       {ECO:0000244|PDB:1LOX}.
 HELIX       391    394       {ECO:0000244|PDB:1LOX}.
 HELIX       397    404       {ECO:0000244|PDB:1LOX}.
 TURN        405    408       {ECO:0000244|PDB:1LOX}.
 HELIX       414    418       {ECO:0000244|PDB:1LOX}.
 TURN        420    424       {ECO:0000244|PDB:1LOX}.
 HELIX       425    434       {ECO:0000244|PDB:1LOX}.
 HELIX       439    442       {ECO:0000244|PDB:1LOX}.
 HELIX       444    450       {ECO:0000244|PDB:1LOX}.
 HELIX       460    480       {ECO:0000244|PDB:1LOX}.
 TURN        481    483       {ECO:0000244|PDB:1LOX}.
 HELIX       487    491       {ECO:0000244|PDB:1LOX}.
 HELIX       494    504       {ECO:0000244|PDB:1LOX}.
 TURN        505    509       {ECO:0000244|PDB:1LOX}.
 HELIX       511    514       {ECO:0000244|PDB:1LOX}.
 HELIX       523    536       {ECO:0000244|PDB:1LOX}.
 HELIX       539    545       {ECO:0000244|PDB:1LOX}.
 HELIX       548    551       {ECO:0000244|PDB:1LOX}.
 STRAND      552    554       {ECO:0000244|PDB:1LOX}.
 HELIX       555    557       {ECO:0000244|PDB:1LOX}.
 STRAND      568    570       {ECO:0000244|PDB:1LOX}.
 HELIX       574    580       {ECO:0000244|PDB:1LOX}.
 HELIX       584    596       {ECO:0000244|PDB:1LOX}.
 HELIX       618    643       {ECO:0000244|PDB:1LOX}.
 STRAND      645    647       {ECO:0000244|PDB:1LOX}.
 TURN        654    656       {ECO:0000244|PDB:1LOX}.
 STRAND      657    660       {ECO:0000244|PDB:1LOX}.
 SEQUENCE   663 AA;  75310 MW;  C3391E1E6E7930BF CRC64;
 MGVYRVCVST GASIYAGSKN KVELWLVGQH GEVELGSCLR PTRNKEEEFK VNVSKYLGSL
 LFVRLRKKHF LKEDAWFCNW ISVQALGAAE DKYWFPCYRW VVGDGVQSLP VGTGCTTVGD
 PQGLFQKHRE QELEERRKLY QWGSWKEGLI LNVAGSKLTD LPVDERFLED KKIDFEASLA
 WGLAELALKN SLNILAPWKT LDDFNRIFWC GRSKLARRVR DSWQEDSLFG YQFLNGANPM
 LLRRSVQLPA RLVFPPGMEE LQAQLEKELK AGTLFEADFA LLDNIKANVI LYCQQYLAAP
 LVMLKLQPDG KLMPMVIQLH LPKIGSSPPP LFLPTDPPMV WLLAKCWVRS SDFQVHELNS
 HLLRGHLMAE VFTVATMRCL PSIHPVFKLI VPHLRYTLEI NVRARNGLVS DFGIFDQIMS
 TGGGGHVQLL QQAGAFLTYR SFCPPDDLAD RGLLGVESSF YAQDALRLWE IISRYVQGIM
 GLYYKTDEAV RDDLELQSWC REITEIGLQG AQKQGFPTSL QSVAQACHFV TMCIFTCTGQ
 HSSIHLGQLD WFTWVPNAPC TMRLPPPTTK DATLETVMAT LPNLHQSSLQ MSIVWQLGRD
 QPIMVPLGQH QEEYFSGPEP RAVLEKFREE LAIMDKEIEV RNEKLDIPYE YLRPSIVENS
 VAI

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