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P16469

- LOX15_PIG

UniProt

P16469 - LOX15_PIG

Protein

Arachidonate 15-lipoxygenase

Gene

ALOX15

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 3 (16 Oct 2013)
      Previous versions | rss
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    Functioni

    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.1 Publication

    Catalytic activityi

    Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.1 Publication
    Arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate.1 Publication

    Cofactori

    Binds 1 iron ion per subunit.1 PublicationPROSITE-ProRule annotation

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi361 – 3611Iron; catalytic
    Metal bindingi366 – 3661Iron; catalytic
    Metal bindingi541 – 5411Iron; catalytic
    Metal bindingi545 – 5451Iron; catalytic
    Metal bindingi663 – 6631Iron; via carboxylate; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. arachidonate 12-lipoxygenase activity Source: UniProtKB
    2. arachidonate 15-lipoxygenase activity Source: UniProtKB
    3. iron ion binding Source: UniProtKB
    4. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic cell clearance Source: UniProtKB
    2. arachidonic acid metabolic process Source: UniProtKB
    3. bone mineralization Source: UniProtKB
    4. cellular response to calcium ion Source: UniProtKB
    5. cellular response to interleukin-13 Source: UniProtKB
    6. linoleic acid metabolic process Source: UniProtKB
    7. lipoxin A4 biosynthetic process Source: UniProtKB
    8. lipoxygenase pathway Source: UniProtKB
    9. negative regulation of adaptive immune response Source: UniProtKB
    10. ossification Source: UniProtKB
    11. phosphatidylethanolamine biosynthetic process Source: UniProtKB
    12. positive regulation of actin filament polymerization Source: UniProtKB
    13. positive regulation of cell-substrate adhesion Source: UniProtKB
    14. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    15. regulation of engulfment of apoptotic cell Source: UniProtKB
    16. regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
    17. response to endoplasmic reticulum stress Source: UniProtKB
    18. wound healing Source: UniProtKB

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Fatty acid metabolism, Lipid metabolism

    Keywords - Ligandi

    Calcium, Iron, Lipid-binding, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_208437. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_215820. Synthesis of 15-eicosatetraenoic acid derivatives.
    REACT_226186. Synthesis of 12-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00881.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arachidonate 15-lipoxygenase (EC:1.13.11.33)
    Short name:
    15-LOX
    Alternative name(s):
    12/15-lipoxygenase
    Arachidonate 12-lipoxygenase, leukocyte-type (EC:1.13.11.31)
    Short name:
    12-LOX
    Arachidonate omega-6 lipoxygenase
    Erythroid cell-specific 15-lipoxygenase
    Gene namesi
    Name:ALOX15
    OrganismiSus scrofa (Pig)
    Taxonomic identifieri9823 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
    ProteomesiUP000008227: Chromosome 12

    Subcellular locationi

    Cytoplasmcytosol By similarity. Cell membrane By similarity; Peripheral membrane protein By similarity. Lipid droplet By similarity
    Note: Predominantly cytosolic; becomes enriched at membranes upon calcium binding. Translocates from the cytosol to the plasma membrane when stimulated by IL13/interleukin-13 and in macrophages binding apoptotic cells By similarity.By similarity

    GO - Cellular componenti

    1. cytosol Source: UniProtKB
    2. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
    3. lipid particle Source: UniProtKB
    4. membrane Source: UniProtKB
    5. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Lipid droplet, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi106 – 1061I → V: No effect on the stereoselectivity of the oxygenation reaction. 1 Publication
    Mutagenesisi128 – 1281H → L: No specific effect on enzymatic activity and iron-binding. 1 Publication
    Mutagenesisi356 – 3561H → L: No specific effect on enzymatic activity and iron-binding. 1 Publication
    Mutagenesisi361 – 3611H → L or Q: Loss of enzymatic activity and iron-binding. 1 Publication
    Mutagenesisi366 – 3661H → L: Loss of enzymatic activity and iron-binding. 1 Publication
    Mutagenesisi384 – 3841H → L: Labile enzyme with normal enzymatic activity. 1 Publication
    Mutagenesisi393 – 3931H → L: Labile enzyme with loss of enzymatic activity. 1 Publication
    Mutagenesisi398 – 3981M → L: No effect on the stereoselectivity of the oxygenation reaction. 1 Publication
    Mutagenesisi418 – 4181V → I: Alters the stereoselectivity of the oxygenation reaction. Changes the stereoselectivity of the oxygenation toward the production of (15S)-HPETE; when associated with M-419. 1 Publication
    Mutagenesisi419 – 4191V → M: Alters the stereoselectivity of the oxygenation reaction. Changes the stereoselectivity of the oxygenation toward the production of (15S)-HPETE; when associated with I-418. 1 Publication
    Mutagenesisi426 – 4261H → L: Decreased enzymatic activity without effect on iron-binding. 1 Publication
    Mutagenesisi533 – 5331C → S: No specific effect on enzymatic activity and iron-binding. 1 Publication
    Mutagenesisi541 – 5411H → L: Loss of enzymatic activity and iron-binding. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 663662Arachidonate 15-lipoxygenasePRO_0000220684Add
    BLAST

    Proteomic databases

    PaxDbiP16469.

    Expressioni

    Tissue specificityi

    Leukocytes, pituitary gland, lung and in very small amount in jejunum and spleen.

    Interactioni

    Subunit structurei

    Interacts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade.By similarity

    Protein-protein interaction databases

    STRINGi9823.ENSSSCP00000018988.

    Structurei

    Secondary structure

    1
    663
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi126 – 13914
    Helixi158 – 1603
    Helixi163 – 1653
    Helixi169 – 19325
    Helixi201 – 2077
    Helixi214 – 2229
    Helixi226 – 23510
    Helixi259 – 27012
    Beta strandi274 – 2785
    Helixi280 – 2823
    Beta strandi301 – 3066
    Beta strandi312 – 3187
    Helixi338 – 35821
    Helixi359 – 3657
    Helixi366 – 37914
    Helixi385 – 3906
    Helixi391 – 3944
    Helixi397 – 40711
    Helixi414 – 4185
    Turni420 – 4245
    Helixi425 – 43612
    Helixi440 – 4423
    Helixi444 – 4507
    Helixi460 – 48324
    Helixi487 – 4915
    Helixi494 – 50512
    Turni506 – 5094
    Helixi512 – 5143
    Helixi523 – 53715
    Helixi539 – 5457
    Helixi548 – 5514
    Beta strandi552 – 5543
    Helixi555 – 5573
    Beta strandi568 – 5703
    Helixi574 – 5807
    Helixi584 – 59815
    Helixi618 – 64326
    Beta strandi645 – 6473
    Turni654 – 6563
    Beta strandi657 – 6604

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3RDEX-ray1.89A/B/C/D112-663[»]
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 115114PLATPROSITE-ProRule annotationAdd
    BLAST
    Domaini116 – 663548LipoxygenasePROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The PLAT domain can bind calcium ions; this promotes association with membranes.By similarity

    Sequence similaritiesi

    Belongs to the lipoxygenase family.Curated
    Contains 1 lipoxygenase domain.PROSITE-ProRule annotation
    Contains 1 PLAT domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG133298.
    GeneTreeiENSGT00550000074415.
    HOGENOMiHOG000234358.
    HOVERGENiHBG005150.
    KOiK00460.
    OMAiLTCWKDL.
    OrthoDBiEOG7B05CG.
    TreeFamiTF105320.

    Family and domain databases

    Gene3Di2.60.60.20. 1 hit.
    InterProiIPR008976. Lipase_LipOase.
    IPR000907. LipOase.
    IPR013819. LipOase_C.
    IPR020834. LipOase_CS.
    IPR020833. LipOase_Fe_BS.
    IPR001885. LipOase_mml.
    IPR001024. PLAT/LH2_dom.
    [Graphical view]
    PANTHERiPTHR11771. PTHR11771. 1 hit.
    PfamiPF00305. Lipoxygenase. 2 hits.
    PF01477. PLAT. 1 hit.
    [Graphical view]
    PRINTSiPR00087. LIPOXYGENASE.
    PR00467. MAMLPOXGNASE.
    SMARTiSM00308. LH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF48484. SSF48484. 1 hit.
    SSF49723. SSF49723. 1 hit.
    PROSITEiPS00711. LIPOXYGENASE_1. 1 hit.
    PS00081. LIPOXYGENASE_2. 1 hit.
    PS51393. LIPOXYGENASE_3. 1 hit.
    PS50095. PLAT. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P16469-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGLYRVRVST GSSFYAGSQN QVQLWLVGQH GEAALGWCLR PARGKETEFS    50
    VDVSEYLGPL LFVKLRKRHL LQDDAWFCNW ISVQGPGANG DEFRFPCYRW 100
    VEGDRILSLP EGTARTVVDD PQGLFKKHRE EELAERRKLY RWGNWKDGLI 150
    LNIASTGIHD LPVDERFLED KRIDFEASLA KGLADLAVKD SLNVLMSWNS 200
    LDSFNRIFWC GQSKLAERVR DSWKEDALFG YQFLNGTNPM LLRHSVELPA 250
    RLKFPPGMEE LQAQLEKELQ GGTLFEADFS LLDGIKANVI LCSQQYLAVP 300
    LVMLKLQPDG KLLPMVIQLQ LPHEGSPLPP LFLPTDPPMV WLLAKCWVRS 350
    SDFQLHELHS HLLRGHLMAE VIAVATMRCL PSIHPIFKLL IPHFRYTMEI 400
    NVRARNGLVS DLGIFDQVVS TGGGGHVELL RRAAALLTYS SFCPPDDLAD 450
    RGLLGVESSF YAQDALRLWE VISRYVEGIV SLHYKTDESV KEDLELQAWC 500
    REFTEIGLLG AQDRGFPVSL QSKEQLCHFV TMCIFTCTGQ HSSNHLGQLD 550
    WYSWVPNAPC TMRLPPPTTK DATLETVMAT LPNFHQASLQ MSITWQLGRC 600
    QPTMVALGQH EEEYFSGPGP KAVLTKFREE LAALDKDIEV RNAKLALPYE 650
    YLRPSRVENS VAI 663
    Length:663
    Mass (Da):75,004
    Last modified:October 16, 2013 - v3
    Checksum:i5E3864A7A3FDEF71
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti218 – 2181R → Q in AAA31068. (PubMed:2315307)Curated
    Sequence conflicti218 – 2181R → Q in BAA01471. (PubMed:2315307)Curated
    Sequence conflicti323 – 3231H → R in AAA31068. (PubMed:2315307)Curated
    Sequence conflicti323 – 3231H → R in BAA01471. (PubMed:2315307)Curated
    Sequence conflicti494 – 4941L → F in AAA31068. (PubMed:2315307)Curated
    Sequence conflicti494 – 4941L → F in BAA01471. (PubMed:2315307)Curated
    Sequence conflicti553 – 5531S → T in AAA31068. (PubMed:2315307)Curated
    Sequence conflicti553 – 5531S → T in BAA01471. (PubMed:2315307)Curated
    Sequence conflicti623 – 6231V → G in BAA01471. (PubMed:2315307)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M31417 mRNA. Translation: AAA31068.1.
    D10621 Genomic DNA. Translation: BAA01471.1.
    CU972403 Genomic DNA. No translation available.
    PIRiA35087.
    RefSeqiNP_999096.1. NM_213931.1.
    UniGeneiSsc.10974.

    Genome annotation databases

    EnsembliENSSSCT00000019506; ENSSSCP00000018988; ENSSSCG00000017923.
    GeneIDi396971.
    KEGGissc:396971.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M31417 mRNA. Translation: AAA31068.1 .
    D10621 Genomic DNA. Translation: BAA01471.1 .
    CU972403 Genomic DNA. No translation available.
    PIRi A35087.
    RefSeqi NP_999096.1. NM_213931.1.
    UniGenei Ssc.10974.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3RDE X-ray 1.89 A/B/C/D 112-663 [» ]
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9823.ENSSSCP00000018988.

    Chemistry

    BindingDBi P16469.
    ChEMBLi CHEMBL2381.

    Proteomic databases

    PaxDbi P16469.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSSSCT00000019506 ; ENSSSCP00000018988 ; ENSSSCG00000017923 .
    GeneIDi 396971.
    KEGGi ssc:396971.

    Organism-specific databases

    CTDi 239.

    Phylogenomic databases

    eggNOGi NOG133298.
    GeneTreei ENSGT00550000074415.
    HOGENOMi HOG000234358.
    HOVERGENi HBG005150.
    KOi K00460.
    OMAi LTCWKDL.
    OrthoDBi EOG7B05CG.
    TreeFami TF105320.

    Enzyme and pathway databases

    UniPathwayi UPA00881 .
    Reactomei REACT_208437. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_215820. Synthesis of 15-eicosatetraenoic acid derivatives.
    REACT_226186. Synthesis of 12-eicosatetraenoic acid derivatives.

    Family and domain databases

    Gene3Di 2.60.60.20. 1 hit.
    InterProi IPR008976. Lipase_LipOase.
    IPR000907. LipOase.
    IPR013819. LipOase_C.
    IPR020834. LipOase_CS.
    IPR020833. LipOase_Fe_BS.
    IPR001885. LipOase_mml.
    IPR001024. PLAT/LH2_dom.
    [Graphical view ]
    PANTHERi PTHR11771. PTHR11771. 1 hit.
    Pfami PF00305. Lipoxygenase. 2 hits.
    PF01477. PLAT. 1 hit.
    [Graphical view ]
    PRINTSi PR00087. LIPOXYGENASE.
    PR00467. MAMLPOXGNASE.
    SMARTi SM00308. LH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48484. SSF48484. 1 hit.
    SSF49723. SSF49723. 1 hit.
    PROSITEi PS00711. LIPOXYGENASE_1. 1 hit.
    PS00081. LIPOXYGENASE_2. 1 hit.
    PS51393. LIPOXYGENASE_3. 1 hit.
    PS50095. PLAT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and sequence analysis of the cDNA for arachidonate 12-lipoxygenase of porcine leukocytes."
      Yoshimoto T., Suzuki H., Yamamoto S., Takai T., Yokoyama C., Tanabe T.
      Proc. Natl. Acad. Sci. U.S.A. 87:2142-2146(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Leukocyte.
    2. "Molecular structure and function of the porcine arachidonate 12-lipoxygenase gene."
      Arakawa T., Oshima T., Kishimoto K., Yoshimoto T., Yamamoto S.
      J. Biol. Chem. 267:12188-12191(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. Porcine genome sequencing project
      Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Site-directed mutagenesis studies on the iron-binding domain and the determinant for the substrate oxygenation site of porcine leukocyte arachidonate 12-lipoxygenase."
      Suzuki H., Kishimoto K., Yoshimoto T., Yamamoto S., Kanai F., Ebina Y., Miyatake A., Tanabe T.
      Biochim. Biophys. Acta 1210:308-316(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, IRON-BINDING, MUTAGENESIS OF ILE-106; HIS-128; HIS-356; HIS-361; HIS-366; HIS-384; HIS-393; MET-398; VAL-418; VAL-419; HIS-426; CYS-533 AND HIS-541.
    5. "Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis."
      Xu S., Mueser T.C., Marnett L.J., Funk M.O. Jr.
      Structure 20:1490-1497(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 112-663 IN COMPLEX WITH INHIBITOR, IRON-BINDING.

    Entry informationi

    Entry nameiLOX15_PIG
    AccessioniPrimary (citable) accession number: P16469
    Secondary accession number(s): F1RFT4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: October 16, 2013
    Last modified: October 1, 2014
    This is version 119 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3