Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q02759

- LOX15_RAT

UniProt

Q02759 - LOX15_RAT

Protein

Arachidonate 15-lipoxygenase

Gene

Alox15

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 3 (16 Oct 2013)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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.4 Publications

    Catalytic activityi

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

    Cofactori

    Binds 1 iron ion per subunit.

    Pathwayi

    Sites

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

    GO - Molecular functioni

    1. arachidonate 12-lipoxygenase activity Source: RGD
    2. arachidonate 15-lipoxygenase activity Source: RGD
    3. hepoxilin A3 synthase activity Source: RGD
    4. hepoxilin-epoxide hydrolase activity Source: UniProtKB
    5. iron ion binding Source: UniProtKB
    6. phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
    7. potassium channel inhibitor activity 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. fatty acid oxidation Source: UniProtKB
    7. hepoxilin biosynthetic process Source: UniProtKB
    8. icosanoid biosynthetic process Source: UniProtKB
    9. lipoxin A4 biosynthetic process Source: UniProtKB
    10. lipoxygenase pathway Source: RGD
    11. negative regulation of adaptive immune response Source: UniProtKB
    12. negative regulation of apoptotic process Source: UniProtKB
    13. negative regulation of cell volume Source: UniProtKB
    14. ossification Source: UniProtKB
    15. phosphatidylethanolamine biosynthetic process Source: UniProtKB
    16. positive regulation of actin filament polymerization Source: UniProtKB
    17. positive regulation of cell growth Source: UniProtKB
    18. positive regulation of cell proliferation Source: UniProtKB
    19. positive regulation of cell-substrate adhesion Source: UniProtKB
    20. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    21. positive regulation of heterotypic cell-cell adhesion Source: RGD
    22. regulation of engulfment of apoptotic cell Source: UniProtKB
    23. regulation of membrane potential Source: UniProtKB
    24. regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
    25. response to endoplasmic reticulum stress Source: UniProtKB
    26. 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_197237. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_198843. Synthesis of 12-eicosatetraenoic acid derivatives.
    REACT_198846. Synthesis of 15-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
    Gene namesi
    Name:Alox15
    Synonyms:Alox12l
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi70493. Alox15.

    Subcellular locationi

    Cytoplasmcytosol 1 Publication. 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
    6. sarcolemma Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Lipid droplet, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 663662Arachidonate 15-lipoxygenasePRO_0000220687Add
    BLAST

    Proteomic databases

    PaxDbiQ02759.
    PRIDEiQ02759.

    Expressioni

    Tissue specificityi

    Detected in leukocytes, lung and aorta.1 Publication

    Gene expression databases

    GenevestigatoriQ02759.

    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

    STRINGi10116.ENSRNOP00000026038.

    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.
    InParanoidiQ02759.
    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.

    Q02759-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGVYRIRVST GDSKYAGSNN EVYLWLVGQH GEASLGKLLR PCRDSEAEFK    50
    VDVSEYLGPL LFVRVQKWHY LTDDAWFCNW ISVKGPGDQG SEYMFPCYRW 100
    VQGRSILSLP EGTGCTVVED SQGLFRKHRE EELEERRSLY RWGNWKDGSI 150
    LNVAAASISD LPVDQRFRED KRIEFEASQV IGVMDTVVNF PINTVTCWKS 200
    LDDFNCVFKS GHTKMAERVR NSWKEDAFFG YQFLNGANPM VLKRSTCLPA 250
    RLVFPPGMEK LQAQLNKELQ KGTLFEADFF LLDGIKANVI LCSQQYLAAP 300
    LVMLKLMPDG QLLPIAIQLE LPKTGSTPPP IFTPSDPPMD WLLAKCWVRS 350
    SDLQLHELQA HLLRGHLMAE VFAVATMRCL PSVHPVFKLL VPHLLYTMEI 400
    NVRARSDLIS ERGFFDKAMS TGGGGHLDLL KQAGAFLTYC SLCPPDDLAE 450
    RGLLDIETCF YAKDALRLWQ IMNRYVVGMF NLHYKTDKAV QDDYELQSWC 500
    REITDIGLQG AQDRGFPTSL QSRAQACYFI TMCIFTCTAQ HSSVHLGQLD 550
    WFYWVPNAPC TMRLPPPTTK EATMEKLMAT LPNPNQSTLQ INVVWLLGRR 600
    QAVMVPLGQH SEEHFPNPEA KAVLKKFREE LAALDKEIEI RNKSLDIPYE 650
    YLRPSMVENS VAI 663
    Length:663
    Mass (Da):75,378
    Last modified:October 16, 2013 - v3
    Checksum:iC732D3EB22CA0411
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti55 – 551E → G in AAB30132. (PubMed:8117750)Curated
    Sequence conflicti371 – 3711V → L in AAA41532. (PubMed:8444196)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L06040 mRNA. Translation: AAA41532.1.
    S69383 mRNA. Translation: AAB30132.1.
    AABR06064408 Genomic DNA. No translation available.
    PIRiI52462.
    S30051.
    RefSeqiNP_112272.2. NM_031010.2.
    UniGeneiRn.11318.

    Genome annotation databases

    EnsembliENSRNOT00000026038; ENSRNOP00000026038; ENSRNOG00000019183.
    GeneIDi81639.
    KEGGirno:81639.
    UCSCiRGD:70493. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L06040 mRNA. Translation: AAA41532.1 .
    S69383 mRNA. Translation: AAB30132.1 .
    AABR06064408 Genomic DNA. No translation available.
    PIRi I52462.
    S30051.
    RefSeqi NP_112272.2. NM_031010.2.
    UniGenei Rn.11318.

    3D structure databases

    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000026038.

    Chemistry

    BindingDBi Q02759.
    ChEMBLi CHEMBL2741.

    Proteomic databases

    PaxDbi Q02759.
    PRIDEi Q02759.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000026038 ; ENSRNOP00000026038 ; ENSRNOG00000019183 .
    GeneIDi 81639.
    KEGGi rno:81639.
    UCSCi RGD:70493. rat.

    Organism-specific databases

    CTDi 246.
    RGDi 70493. Alox15.

    Phylogenomic databases

    eggNOGi NOG133298.
    GeneTreei ENSGT00550000074415.
    HOGENOMi HOG000234358.
    HOVERGENi HBG005150.
    InParanoidi Q02759.
    KOi K00460.
    OMAi LTCWKDL.
    OrthoDBi EOG7B05CG.
    TreeFami TF105320.

    Enzyme and pathway databases

    UniPathwayi UPA00881 .
    Reactomei REACT_197237. Synthesis of Leukotrienes (LT) and Eoxins (EX).
    REACT_198843. Synthesis of 12-eicosatetraenoic acid derivatives.
    REACT_198846. Synthesis of 15-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    NextBioi 35583133.

    Gene expression databases

    Genevestigatori Q02759.

    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. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
      Strain: Sprague-Dawley.
      Tissue: Brain.
    2. "Arachidonate 12-lipoxygenase of rat pineal glands: catalytic properties and primary structure deduced from its cDNA."
      Hada T., Hagiya H., Suzuki H., Arakawa T., Nakamura M., Matsuda S., Yoshimoto T., Yamamoto S., Azekawa T., Morita Y., Ishimura K., Kim H.Y.
      Biochim. Biophys. Acta 1211:221-228(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
      Tissue: Pineal gland.
    3. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
      Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
      , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
      Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: Brown Norway.
    4. "The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity."
      Nigam S., Patabhiraman S., Ciccoli R., Ishdorj G., Schwarz K., Petrucev B., Kuehn H., Haeggstroem J.Z.
      J. Biol. Chem. 279:29023-29030(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN HEPOXILIN A3 SYNTHESIS.
    5. "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia."
      Gregus A.M., Dumlao D.S., Wei S.C., Norris P.C., Catella L.C., Meyerstein F.G., Buczynski M.W., Steinauer J.J., Fitzsimmons B.L., Yaksh T.L., Dennis E.A.
      FASEB J. 27:1939-1949(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiLOX15_RAT
    AccessioniPrimary (citable) accession number: Q02759
    Secondary accession number(s): F1MA51
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: October 16, 2013
    Last modified: October 1, 2014
    This is version 122 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

    Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3