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Protein

Arachidonate 8S-lipoxygenase

Gene

Alox8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

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

    Keywordsi

    Molecular functionDioxygenase, Oxidoreductase
    Biological processLipid metabolism
    LigandCalcium, Iron, Lipid-binding, Metal-binding

    Enzyme and pathway databases

    ReactomeiR-MMU-2142770 Synthesis of 15-eicosatetraenoic acid derivatives
    UniPathwayi
    UPA00881

    Chemistry databases

    SwissLipidsiSLP:000000650
    SLP:000000742

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
    Proteomesi
    • UP000000589 Componenti: Chromosome 11

    Organism-specific databases

    MGIiMGI:1098228 Alox8

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    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 Expressed in 41 organ(s), highest expression level in skin of back
    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

    Phylogenomic databases

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

    Family and domain databases

    InterProiView protein in InterPro
    IPR000907 LipOase
    IPR013819 LipOase_C
    IPR036226 LipOase_C_sf
    IPR020834 LipOase_CS
    IPR020833 LipOase_Fe_BS
    IPR001885 LipOase_mml
    IPR001024 PLAT/LH2_dom
    IPR036392 PLAT/LH2_dom_sf
    PANTHERiPTHR11771 PTHR11771, 1 hit
    PfamiView protein in Pfam
    PF00305 Lipoxygenase, 1 hit
    PF01477 PLAT, 1 hit
    PRINTSiPR00087 LIPOXYGENASE
    PR00467 MAMLPOXGNASE
    SMARTiView protein in SMART
    SM00308 LH2, 1 hit
    SUPFAMiSSF48484 SSF48484, 1 hit
    SSF49723 SSF49723, 1 hit
    PROSITEiView protein in PROSITE
    PS00711 LIPOXYGENASE_1, 1 hit
    PS00081 LIPOXYGENASE_2, 1 hit
    PS51393 LIPOXYGENASE_3, 1 hit
    PS50095 PLAT, 1 hit

    Sequence (1+)i

    Sequence statusi: Complete.

    This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

    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

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    B1ASX6B1ASX6_MOUSE
    Arachidonate 8S-lipoxygenase
    Alox8
    648Annotation score:

    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 No translation available.
    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

    Similar proteinsi

    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 No translation available.
    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
    SLP:000000742

    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
    OMAiEFSIHEA
    OrthoDBiEOG091G04A4
    PhylomeDBiO35936
    TreeFamiTF105320

    Enzyme and pathway databases

    UniPathwayi
    UPA00881

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

    Miscellaneous databases

    ChiTaRSiAlox8 mouse
    PROiPR:O35936
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSMUSG00000020891 Expressed in 41 organ(s), highest expression level in skin of back
    CleanExiMM_ALOX8
    ExpressionAtlasiO35936 baseline and differential
    GenevisibleiO35936 MM

    Family and domain databases

    InterProiView protein in InterPro
    IPR000907 LipOase
    IPR013819 LipOase_C
    IPR036226 LipOase_C_sf
    IPR020834 LipOase_CS
    IPR020833 LipOase_Fe_BS
    IPR001885 LipOase_mml
    IPR001024 PLAT/LH2_dom
    IPR036392 PLAT/LH2_dom_sf
    PANTHERiPTHR11771 PTHR11771, 1 hit
    PfamiView protein in Pfam
    PF00305 Lipoxygenase, 1 hit
    PF01477 PLAT, 1 hit
    PRINTSiPR00087 LIPOXYGENASE
    PR00467 MAMLPOXGNASE
    SMARTiView protein in SMART
    SM00308 LH2, 1 hit
    SUPFAMiSSF48484 SSF48484, 1 hit
    SSF49723 SSF49723, 1 hit
    PROSITEiView protein in PROSITE
    PS00711 LIPOXYGENASE_1, 1 hit
    PS00081 LIPOXYGENASE_2, 1 hit
    PS51393 LIPOXYGENASE_3, 1 hit
    PS50095 PLAT, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiALOX8_MOUSE
    AccessioniPrimary (citable) accession number: O35936
    Secondary accession number(s): B1ASX5
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: January 1, 1998
    Last modified: November 7, 2018
    This is version 156 of the entry and version 1 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    2. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    3. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

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