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P39655

- LOX12_MOUSE

UniProt

P39655 - LOX12_MOUSE

Protein

Arachidonate 12-lipoxygenase, 12S-type

Gene

Alox12

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 4 (11 Sep 2007)
      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. Mainly converts arachidonic acid to (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation.1 Publication

    Catalytic activityi

    Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.1 Publication
    (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (5S,6R,15S)-trihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate.1 Publication
    (7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa-7,9,11,14-tetraenoate + H2O = (5S,14R,15S)-trihydroxy-(6E,8Z,10E,12E)-eicosatetraenoate.1 Publication

    Cofactori

    Binds 1 iron ion per subunit.

    Enzyme regulationi

    Activated by EGF.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi360 – 3601Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi365 – 3651Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi540 – 5401Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi544 – 5441Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi663 – 6631Iron; via carboxylate; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. arachidonate 12-lipoxygenase activity Source: UniProtKB
    2. hepoxilin-epoxide hydrolase activity Source: UniProtKB
    3. iron ion binding Source: InterPro
    4. linoleate 13S-lipoxygenase activity Source: Ensembl

    GO - Biological processi

    1. aging Source: Ensembl
    2. arachidonic acid metabolic process Source: UniProtKB
    3. cellular component movement Source: UniProtKB
    4. cellular response to lipid Source: Ensembl
    5. establishment of skin barrier Source: UniProtKB
    6. fatty acid oxidation Source: UniProtKB
    7. hepoxilin biosynthetic process Source: UniProtKB
    8. leukotriene A4 metabolic process Source: UniProtKB
    9. linoleic acid metabolic process Source: UniProtKB
    10. lipoxin A4 biosynthetic process Source: UniProtKB
    11. lipoxin B4 biosynthetic process Source: UniProtKB
    12. lipoxygenase pathway Source: UniProtKB
    13. negative regulation of apoptotic process Source: UniProtKB
    14. negative regulation of muscle cell apoptotic process Source: UniProtKB
    15. negative regulation of platelet aggregation Source: UniProtKB
    16. positive regulation of angiogenesis Source: UniProtKB
    17. positive regulation of apoptotic process Source: UniProtKB
    18. positive regulation of cell adhesion Source: UniProtKB
    19. positive regulation of cell growth Source: UniProtKB
    20. positive regulation of cell migration Source: UniProtKB
    21. positive regulation of cell proliferation Source: UniProtKB
    22. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
    23. positive regulation of endothelial cell differentiation Source: Ensembl
    24. positive regulation of endothelial cell migration Source: Ensembl
    25. positive regulation of gene expression Source: Ensembl
    26. positive regulation of mitochondrial depolarization Source: Ensembl
    27. positive regulation of smooth muscle cell proliferation Source: Ensembl
    28. positive regulation of vasodilation Source: Ensembl

    Keywords - Molecular functioni

    Dioxygenase, Hydrolase, Oxidoreductase

    Keywords - Biological processi

    Fatty acid metabolism, Lipid metabolism

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_196544. Synthesis of Lipoxins (LX).
    REACT_196560. Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
    REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00881.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arachidonate 12-lipoxygenase, 12S-type (EC:1.13.11.31)
    Short name:
    12S-LOX
    Short name:
    12S-lipoxygenase
    Alternative name(s):
    Lipoxin synthase 12-LO (EC:3.3.2.-)
    Platelet-type lipoxygenase 12
    Short name:
    P-12LO
    Gene namesi
    Name:Alox12
    Synonyms:Alox12p
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:87998. Alox12.

    Subcellular locationi

    Cytoplasmcytosol 1 Publication. Membrane By similarity
    Note: Membrane association is stimulated by EGF.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: UniProtKB-SubCell
    3. membrane Source: UniProtKB
    4. sarcolemma Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice are fertile and appear to exhibit no gross abnormalities. However, they display increased aggregation of platelets in response to ADP. They also display a mild basal transepidermal water loss.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi663 – 6631I → D, R, K or G: Loss of activity. 1 Publication
    Mutagenesisi663 – 6631I → S or N: Little activity (8-15%). 1 Publication
    Mutagenesisi663 – 6631I → V: Nearly full activity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 663663Arachidonate 12-lipoxygenase, 12S-typePRO_0000220683Add
    BLAST

    Proteomic databases

    MaxQBiP39655.
    PaxDbiP39655.
    PRIDEiP39655.

    PTM databases

    PhosphoSiteiP39655.

    Expressioni

    Tissue specificityi

    Found primarily in platelets and in microsomal and cytosolic fractions of the epidermis (at protein level).3 Publications

    Gene expression databases

    ArrayExpressiP39655.
    BgeeiP39655.
    CleanExiMM_ALOX12.
    GenevestigatoriP39655.

    Interactioni

    Structurei

    3D structure databases

    ProteinModelPortaliP39655.
    SMRiP39655. Positions 2-663.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 114113PLATPROSITE-ProRule annotationAdd
    BLAST
    Domaini115 – 663549LipoxygenasePROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiNOG69653.
    GeneTreeiENSGT00550000074415.
    HOGENOMiHOG000234358.
    HOVERGENiHBG005150.
    InParanoidiP39655.
    KOiK00458.
    OMAiQNQLCHF.
    OrthoDBiEOG7B05CG.
    PhylomeDBiP39655.
    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. 1 hit.
    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.

    P39655-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGRYRVRVVT GAWLFSGSLN LVRLWLVGEH REAKLELQLR PARGKEEEFD    50
    FDVPEDLGPL QFVKLHKQHT VVDDAWFCNL ITVQGPGTSA EAVFPCYRWV 100
    QGEGILSLPE GTARLAGDNA LDVFQKYREK ELKERQQTYC WATWKEGLPQ 150
    TIAADCKDDL PPNMRFHEEK RLDFEWTLKA GVLEMGLKRV YTLLRSWNHL 200
    EDFDQIFWGQ KSALAEKVHQ CWQEDELFGY QFLNGANPML LRRSTSLPSR 250
    LVLPSGMEEL QAQLEKELKN GSLFEADFIL LDGIPANVIR GEPQYLAAPL 300
    VMLRMDPGGK LLPMAIQIQP PNPSSPAPTL FLPSDPPLAW LLAKIWVRNS 350
    DFQLQELQFH LLNTHLVAEV IAVATMRCLP GLHPIFKLLV PHIRYTMEIN 400
    TRSRTQLISD GGIFDQVVST GGGGHVQLLT RAVAQLTYHS LCPPDDLANR 450
    GLLRIPSALY ARDALQLWEV TARYVKGMVH LFYQSDDIVR GDPELQAWCR 500
    EITEVGLCHA QDRGFPVSFQ SRAQLCHFLT MCVFTCTAQH AAINQGQLDW 550
    YGWVPNAPCT MRMPPPTSKD DVTMETVMGS LPDVQKACLQ MTITWHLGRL 600
    QPDMVPLGHH TEKYFSDPRT KAVLSQFQAD LDNLEKEITA RNEQLDLPYE 650
    YLKPSRIENS ITI 663
    Length:663
    Mass (Da):75,390
    Last modified:September 11, 2007 - v4
    Checksum:i205BE32BE2CF3E87
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti3 – 31R → A in AAA20659. (PubMed:8188678)Curated
    Sequence conflicti112 – 1121T → Q in AAA20659. (PubMed:8188678)Curated
    Sequence conflicti112 – 1121T → Q in AAB36013. (PubMed:7576099)Curated
    Sequence conflicti403 – 4031S → T in AAA20659. (PubMed:8188678)Curated
    Sequence conflicti403 – 4031S → T in AAB36013. (PubMed:7576099)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U04334 mRNA. Translation: AAA20659.1.
    S80446 mRNA. Translation: AAB36013.1.
    AK036898 mRNA. Translation: BAC29629.1.
    AK087724 mRNA. Translation: BAC39981.1.
    AL669869 Genomic DNA. Translation: CAI35235.1.
    S77511 mRNA. Translation: AAB34667.1.
    CCDSiCCDS24942.1.
    PIRiA54075.
    RefSeqiNP_031466.2. NM_007440.4.
    UniGeneiMm.12286.

    Genome annotation databases

    EnsembliENSMUST00000000329; ENSMUSP00000000329; ENSMUSG00000000320.
    GeneIDi11684.
    KEGGimmu:11684.
    UCSCiuc007juj.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U04334 mRNA. Translation: AAA20659.1 .
    S80446 mRNA. Translation: AAB36013.1 .
    AK036898 mRNA. Translation: BAC29629.1 .
    AK087724 mRNA. Translation: BAC39981.1 .
    AL669869 Genomic DNA. Translation: CAI35235.1 .
    S77511 mRNA. Translation: AAB34667.1 .
    CCDSi CCDS24942.1.
    PIRi A54075.
    RefSeqi NP_031466.2. NM_007440.4.
    UniGenei Mm.12286.

    3D structure databases

    ProteinModelPortali P39655.
    SMRi P39655. Positions 2-663.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P39655.
    ChEMBLi CHEMBL3225.

    PTM databases

    PhosphoSitei P39655.

    Proteomic databases

    MaxQBi P39655.
    PaxDbi P39655.
    PRIDEi P39655.

    Protocols and materials databases

    DNASUi 11684.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000000329 ; ENSMUSP00000000329 ; ENSMUSG00000000320 .
    GeneIDi 11684.
    KEGGi mmu:11684.
    UCSCi uc007juj.1. mouse.

    Organism-specific databases

    CTDi 239.
    MGIi MGI:87998. Alox12.

    Phylogenomic databases

    eggNOGi NOG69653.
    GeneTreei ENSGT00550000074415.
    HOGENOMi HOG000234358.
    HOVERGENi HBG005150.
    InParanoidi P39655.
    KOi K00458.
    OMAi QNQLCHF.
    OrthoDBi EOG7B05CG.
    PhylomeDBi P39655.
    TreeFami TF105320.

    Enzyme and pathway databases

    UniPathwayi UPA00881 .
    Reactomei REACT_196544. Synthesis of Lipoxins (LX).
    REACT_196560. Synthesis of Hepoxilins (HX) and Trioxilins (TrX).
    REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    NextBioi 279319.
    PROi P39655.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P39655.
    Bgeei P39655.
    CleanExi MM_ALOX12.
    Genevestigatori P39655.

    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. 1 hit.
    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. "cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenases."
      Chen X.-S., Kurre U., Jenkins N.A., Copeland N.G., Funk C.D.
      J. Biol. Chem. 269:13979-13987(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-663, TISSUE SPECIFICITY.
      Strain: C57BL/6 and ICR.
      Tissue: Spleen.
    2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Ovary and Vagina.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: C57BL/6J.
    5. "12-lipoxygenase in Lewis lung carcinoma cells: molecular identity, intracellular distribution of activity and protein, and Ca(2+)-dependent translocation from cytosol to membranes."
      Hagmann W., Gao X., Zacharek A., Wojciechowski L.A., Honn K.V.
      Prostaglandins 49:49-62(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 126-218.
      Tissue: Lung.
    6. "Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells."
      Nakamura M., Ueda N., Kishimoto K., Yoshimoto T., Yamamoto S., Ishimura K.
      J. Histochem. Cytochem. 43:237-244(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    7. "Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase."
      Johnson E.N., Brass L.F., Funk C.D.
      Proc. Natl. Acad. Sci. U.S.A. 95:3100-3105(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PLATELET ACTIVATION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
    8. "Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice."
      Johnson E.N., Nanney L.B., Virmani J., Lawson J.A., Funk C.D.
      J. Invest. Dermatol. 112:861-865(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiLOX12_MOUSE
    AccessioniPrimary (citable) accession number: P39655
    Secondary accession number(s): Q8BHG4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: September 11, 2007
    Last modified: October 1, 2014
    This is version 126 of the entry and version 4 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. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3