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Protein

Arachidonate 8S-lipoxygenase

Gene

Alox8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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. Catalyzes the peroxidation of arachidonate and linoleate into (8S)-HPETE and (9S)-HPODE respectively. From arachidonate mainly produces (8S)-HPETE and in addition, minor products derived from (8S)-HPETE itself that may include leukotriene A4 and 8,15-diHPETE. With arachidonate as substrate, has no detectable 15S-lipoxygenase activity and only displays a 8S-lipoxygenase activity. However, it may have a 15S-lipoxygenase activity with (8S)-HPETE to produce (8S,15S)-diHPETE. May also catalyze (15S)-HPETE peroxidation to produce 8,15-diHPETE. May play a role in keratinocyte differentiation through activation of the peroxisome proliferator activated receptor signaling pathway.4 Publications

Catalytic activityi

Arachidonate + O2 = (5Z,9E,11Z,14Z)-8-hydroperoxyicosa-5,9,11,14-tetraenoate.3 Publications

Cofactori

Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation

Kineticsi

The highest catalytic efficiency is observed with arachidonate followed by (8S)-HPETE and(15S)-HPETE with similar efficiencies.

  1. KM=1.2 µM for arachidonate (at pH 7.4 and 25 degrees Celsius)1 Publication
  2. KM=2.1 µM for (8S)-HPETE (at pH 7.4 and 25 degrees Celsius)1 Publication
  3. KM=5.7 µM for (8S)-HETE (at pH 7.4 and 25 degrees Celsius)1 Publication
  4. KM=39 µM for (15S)-HPETE (at pH 7.4 and 25 degrees Celsius)1 Publication
  5. KM=15 µM for (15S)-HETE (at pH 7.4 and 25 degrees Celsius)1 Publication

    Pathwayi: hydroperoxy eicosatetraenoic acid biosynthesis

    This protein is involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis, which is part of Lipid metabolism.
    View all proteins of this organism that are known to be involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis and in Lipid metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi15Calcium 1; via carbonyl oxygenBy similarity1
    Metal bindingi17Calcium 1; via carbonyl oxygenBy similarity1
    Metal bindingi39Calcium 2By similarity1
    Metal bindingi40Calcium 2; via carbonyl oxygenBy similarity1
    Metal bindingi42Calcium 2; via carbonyl oxygenBy similarity1
    Metal bindingi44Calcium 2By similarity1
    Metal bindingi86Calcium 1By similarity1
    Metal bindingi87Calcium 1; via carbonyl oxygenBy similarity1
    Metal bindingi374Iron; catalyticPROSITE-ProRule annotation1
    Metal bindingi379Iron; catalyticPROSITE-ProRule annotation1
    Metal bindingi554Iron; catalyticPROSITE-ProRule annotation1
    Metal bindingi677Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

    GO - Molecular functioni

    GO - Biological processi

    • arachidonic acid metabolic process Source: UniProtKB
    • linoleic acid metabolic process Source: UniProtKB
    • lipoxygenase pathway Source: UniProtKB
    • negative regulation of cell cycle Source: MGI
    • negative regulation of cell proliferation Source: MGI
    • negative regulation of growth Source: MGI
    • positive regulation of chemokine secretion Source: MGI
    • positive regulation of keratinocyte differentiation Source: UniProtKB
    • positive regulation of macrophage derived foam cell differentiation Source: MGI
    • positive regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Lipid metabolism

    Keywords - Ligandi

    Calcium, Iron, Lipid-binding, Metal-binding

    Enzyme and pathway databases

    ReactomeiR-MMU-2142770. Synthesis of 15-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00881.

    Chemistry databases

    SwissLipidsiSLP:000000650.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arachidonate 8S-lipoxygenase (EC:1.13.11.-)
    Short name:
    8-LOX
    Short name:
    8S-LOX
    Alternative name(s):
    15-lipoxygenase 2
    Short name:
    15-LOX-2
    Arachidonate 15-lipoxygenase B
    Short name:
    15-LOX-B
    Gene namesi
    Name:Alox8
    Synonyms:Alox15b
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 11

    Organism-specific databases

    MGIiMGI:1098228. Alox8.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi374H → L: Loss of enzymatic activity. 1 Publication1
    Mutagenesisi558S → A, H or N: Retains catalytic activity indicating it is not required for iron ligand-binding. 1 Publication1
    Mutagenesisi603Y → D: Changes the stereoselectivity of the oxygenation reaction to produce (15S)-HPETE instead of (8S)-HPETE. Completely changes the stereoselectivity; when associated with V-604. 1 Publication1
    Mutagenesisi604H → V: Changes the stereoselectivity of the oxygenation reaction to produce (15S)-HPETE instead of (8S)-HPETE. Completely changes the stereoselectivity; when associated with D-603. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00002207011 – 677Arachidonate 8S-lipoxygenaseAdd BLAST677

    Proteomic databases

    PaxDbiO35936.
    PRIDEiO35936.

    PTM databases

    PhosphoSitePlusiO35936.

    Expressioni

    Tissue specificityi

    Expressed in epidermis and brain. No expression found in heart, spleen, liver, skeletal muscle, kidney or testis.2 Publications

    Inductioni

    By phorbol ester.1 Publication

    Gene expression databases

    BgeeiENSMUSG00000020891.
    CleanExiMM_ALOX8.
    ExpressionAtlasiO35936. baseline and differential.
    GenevisibleiO35936. MM.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000021262.

    Structurei

    3D structure databases

    ProteinModelPortaliO35936.
    SMRiO35936.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini2 – 125PLATPROSITE-ProRule annotationAdd BLAST124
    Domaini126 – 677LipoxygenasePROSITE-ProRule annotationAdd BLAST552

    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

    eggNOGiENOG410IF0U. Eukaryota.
    ENOG410YN4N. LUCA.
    GeneTreeiENSGT00550000074415.
    HOGENOMiHOG000234358.
    HOVERGENiHBG005150.
    InParanoidiO35936.
    KOiK08022.
    OMAiLVLPYTY.
    OrthoDBiEOG091G04A4.
    PhylomeDBiO35936.
    TreeFamiTF105320.

    Family and domain databases

    Gene3Di2.60.60.20. 1 hit.
    InterProiIPR000907. 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.

    O35936-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAKCRVRVST GEACGAGTWD KVSVSIVGTH GESPLVPLDH LGKEFSAGAE
    60 70 80 90 100
    EDFEVTLPQD VGTVLMLRVH KAPPEVSLPL MSFRSDAWFC RWFELEWLPG
    110 120 130 140 150
    AALHFPCYQW LEGAGELVLR EGAAKVSWQD HHPTLQDQRQ KELESRQKMY
    160 170 180 190 200
    SWKTYIEGWP RCLDHETVKD LDLNIKYSAM KNAKLFFKAH SAYTELKVKG
    210 220 230 240 250
    LLDRTGLWRS LREMRRLFNF RKTPAAEYVF AHWQEDAFFA SQFLNGINPV
    260 270 280 290 300
    LIRRCHSLPN NFPVTDEMVA PVLGPGTSLQ AELEKGSLFL VDHGILSGVH
    310 320 330 340 350
    TNILNGKPQF SAAPMTLLHQ SSGSGPLLPI AIQLKQTPGP DNPIFLPSDD
    360 370 380 390 400
    TWDWLLAKTW VRNSEFYIHE AVTHLLHAHL IPEVFALATL RQLPRCHPLF
    410 420 430 440 450
    KLLIPHIRYT LHINTLAREL LVAPGKLIDK STGLGTGGFS DLIKRNMEQL
    460 470 480 490 500
    NYSVLCLPED IRARGVEDIP GYYYRDDGMQ IWGAIKSFVS EIVSIYYPSD
    510 520 530 540 550
    TSVQDDQELQ AWVREIFSEG FLGRESSGMP SLLDTREALV QYITMVIFTC
    560 570 580 590 600
    SAKHAAVSSG QFDSCVWMPN LPPTMQLPPP TSKGQARPES FIATLPAVNS
    610 620 630 640 650
    SSYHIIALWL LSAEPGDQRP LGHYPDEHFT EDAPRRSVAA FQRKLIQISK
    660 670
    GIRERNRGLA LPYTYLDPPL IENSVSI
    Length:677
    Mass (Da):76,230
    Last modified:January 1, 1998 - v1
    Checksum:i78DB1AC9C2F68399
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural varianti32E → G in clone K12. 1
    Natural varianti38L → M in clone G2. 1
    Natural varianti58P → R in clone K12. 1
    Natural varianti76V → A in clones G2, G5, G11 and K1. 1
    Natural varianti413I → V in clone K7. 1
    Natural varianti536R → Q in clones G2, G5 and G11. 1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U93277 mRNA. Translation: AAC53356.1.
    Y14696 mRNA. Translation: CAA75003.1.
    AK028724 mRNA. Translation: BAC26085.1.
    AL645527 Genomic DNA. Translation: CAI35251.1.
    BC015253 mRNA. Translation: AAH15253.1.
    CCDSiCCDS24886.1.
    RefSeqiNP_033791.1. NM_009661.4.
    UniGeneiMm.289672.

    Genome annotation databases

    EnsembliENSMUST00000021262; ENSMUSP00000021262; ENSMUSG00000020891.
    GeneIDi11688.
    KEGGimmu:11688.
    UCSCiuc007jpl.1. mouse.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U93277 mRNA. Translation: AAC53356.1.
    Y14696 mRNA. Translation: CAA75003.1.
    AK028724 mRNA. Translation: BAC26085.1.
    AL645527 Genomic DNA. Translation: CAI35251.1.
    BC015253 mRNA. Translation: AAH15253.1.
    CCDSiCCDS24886.1.
    RefSeqiNP_033791.1. NM_009661.4.
    UniGeneiMm.289672.

    3D structure databases

    ProteinModelPortaliO35936.
    SMRiO35936.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000021262.

    Chemistry databases

    SwissLipidsiSLP:000000650.

    PTM databases

    PhosphoSitePlusiO35936.

    Proteomic databases

    PaxDbiO35936.
    PRIDEiO35936.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENSMUST00000021262; ENSMUSP00000021262; ENSMUSG00000020891.
    GeneIDi11688.
    KEGGimmu:11688.
    UCSCiuc007jpl.1. mouse.

    Organism-specific databases

    CTDi11688.
    MGIiMGI:1098228. Alox8.

    Phylogenomic databases

    eggNOGiENOG410IF0U. Eukaryota.
    ENOG410YN4N. LUCA.
    GeneTreeiENSGT00550000074415.
    HOGENOMiHOG000234358.
    HOVERGENiHBG005150.
    InParanoidiO35936.
    KOiK08022.
    OMAiLVLPYTY.
    OrthoDBiEOG091G04A4.
    PhylomeDBiO35936.
    TreeFamiTF105320.

    Enzyme and pathway databases

    UniPathwayiUPA00881.
    ReactomeiR-MMU-2142770. Synthesis of 15-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    ChiTaRSiAlox8. mouse.
    PROiO35936.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000020891.
    CleanExiMM_ALOX8.
    ExpressionAtlasiO35936. baseline and differential.
    GenevisibleiO35936. MM.

    Family and domain databases

    Gene3Di2.60.60.20. 1 hit.
    InterProiIPR000907. 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]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiALOX8_MOUSE
    AccessioniPrimary (citable) accession number: O35936
    Secondary accession number(s): B1ASX5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: January 1, 1998
    Last modified: November 2, 2016
    This is version 144 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Caution

    Despite its homology with human ALOX15B (AC O15296), it seems not to have any 15S-lipoxygenase activity on arachidonate. Based on its catalytic activity it is referred to as the mouse arachidonate 8S-lipoxygenase.Curated

    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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.