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O70582

- LX12B_MOUSE

UniProt

O70582 - LX12B_MOUSE

Protein

Arachidonate 12-lipoxygenase, 12R-type

Gene

Alox12b

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 111 (01 Oct 2014)
      Sequence version 1 (01 Aug 1998)
      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 (12R)-hydroperoxyeicosatetraenoic acid/(12R)-HPETE and minor stereoisomers. In the skin, acts upstream of ALOXE3 on the lineolate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss. May also play a role in the regulation of the expression of airway mucins.4 Publications

    Catalytic activityi

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

    Cofactori

    Binds 1 iron ion per subunit.PROSITE-ProRule annotation

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi398 – 3981Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi403 – 4031Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi578 – 5781Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi582 – 5821Iron; catalyticPROSITE-ProRule annotation
    Metal bindingi701 – 7011Iron; via carboxylate; catalyticPROSITE-ProRule annotation

    GO - Molecular functioni

    1. arachidonate 12-lipoxygenase activity Source: UniProtKB
    2. catalytic activity Source: MGI
    3. iron ion binding Source: InterPro
    4. linoleate 9S-lipoxygenase activity Source: UniProtKB

    GO - Biological processi

    1. arachidonic acid metabolic process Source: UniProtKB
    2. ceramide biosynthetic process Source: UniProtKB
    3. establishment of skin barrier Source: UniProtKB
    4. hepoxilin biosynthetic process Source: UniProtKB
    5. linoleic acid metabolic process Source: UniProtKB
    6. lipoxygenase pathway Source: UniProtKB
    7. oxidation-reduction process Source: UniProtKB
    8. positive regulation of gene expression Source: UniProtKB
    9. positive regulation of MAPK cascade Source: UniProtKB
    10. positive regulation of mucus secretion Source: UniProtKB
    11. protein lipidation Source: UniProtKB
    12. sphingolipid metabolic process Source: UniProtKB

    Keywords - Molecular functioni

    Dioxygenase, Oxidoreductase

    Keywords - Biological processi

    Fatty acid metabolism, Lipid metabolism

    Keywords - Ligandi

    Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.
    UniPathwayiUPA00222.
    UPA00881.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arachidonate 12-lipoxygenase, 12R-type (EC:1.13.11.-)
    Short name:
    12R-LOX
    Short name:
    12R-lipoxygenase
    Alternative name(s):
    Epidermis-type lipoxygenase 12
    Epidermis-type lipoxygenase 2
    Short name:
    e-LOX 2
    Gene namesi
    Name:Alox12b
    Synonyms:Aloxe2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:1274782. Alox12b.

    Subcellular locationi

    Cytoplasm PROSITE-ProRule annotation

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Mice die within 3 to 5 hours after birth due to defective skin barrier function loosing around 30% of body weight within 3 hours. Dehydration through the skin is increased 8 folds. The outside-in barrier acquisition is also affected, the skin remaining permeable at E18.5 while it is impermeable in wild-type mice. The stratum corneum is more tightly packed while other layers are unaffected. Processing of filaggrin/FG is aberrant and the skin displays structural abnormalities. The cornified envelope is more fragile and the ceramide composition of the epidermis is altered.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi390 – 3901F → A: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication
    Mutagenesisi390 – 3901F → W: Loss of enzymatic activity. 1 Publication
    Mutagenesisi441 – 4411G → A: Reduced enzymatic activity and changed stereoselectivity of the oxygenation reaction. 1 Publication
    Mutagenesisi441 – 4411G → V: Loss of enzymatic activity. 1 Publication
    Mutagenesisi455 – 4551A → I or W: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication
    Mutagenesisi631 – 6311V → A or G: Increased enzymatic activity and changed stereoselectivity of the oxygenation reaction to produce (11R)-HPETE preferentially instead of (12R)-HPETE. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 701701Arachidonate 12-lipoxygenase, 12R-typePRO_0000220690Add
    BLAST

    Proteomic databases

    PRIDEiO70582.

    PTM databases

    PhosphoSiteiO70582.

    Expressioni

    Tissue specificityi

    Expressed in skin epidermis and other stratified epithelia including tongue and forestomach. Low levels of expression are found in trachea, brain and lung. Not expressed in intestine, liver, kidney, adipose tissue, muscle or hematopoietic cells.1 Publication

    Developmental stagei

    In the embryo, expression begins at day 15.5.1 Publication

    Gene expression databases

    BgeeiO70582.
    CleanExiMM_ALOX12B.
    GenevestigatoriO70582.

    Structurei

    3D structure databases

    ProteinModelPortaliO70582.
    SMRiO70582. Positions 2-701.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 119118PLATPROSITE-ProRule annotationAdd
    BLAST
    Domaini120 – 701582LipoxygenasePROSITE-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.
    HOGENOMiHOG000234358.
    HOVERGENiHBG005150.
    InParanoidiO70582.
    KOiK08021.
    OMAiYHFPAYQ.
    OrthoDBiEOG7V49XR.
    PhylomeDBiO70582.
    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.

    O70582-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATYKVKVAT GTDFFSGTLD SISLTIVGTQ GESHKQRLNH FGRDFATGAV    50
    DDYTVQCQQD LGELIIIRLH KEPHSFLAKD PWYCNYVQIC APDCRVYHFP 100
    AYQWMDGYET LALREATGKI TADDTLPILL EHRQEEIRAK KDFYHWRVFV 150
    PGLPNYVDIP SYHPPPRRCR NPNRPEWDGY IPGFPILINI KATRFLNSNL 200
    RFSFVKTASF FYRLGPMALA FKLRGLVDRK RSWKRLKDIK NIFPATKSVV 250
    SEYVAEHWTE DSFFGYQYLN GINPGLIRRC TQIPDKFPVT DEMVAPFLGE 300
    GTCLQAELER GNIYLADYRI LDGIPTVELN GQQQHHCAPM CLLHFGPDGN 350
    MMPIAIQLSQ TPGPDCPIFL PNDSEWDWLL AKTWVRYAEF YSHEAVAHLL 400
    ESHLIGEAFC LALLRNLPMC HPLYKLLIPH TRYNVQINSI GRALLLNKGG 450
    LSARAMSLGL EGFAQVMVRG LSELTYKSLC IPNDFVERGV QDLPGYYFRD 500
    DSLAVWYAME RYVTEIITYY YPNDAAVEGD PELQCWVQEI FKECLLGRES 550
    SGFPTCLRTI PELIEYVTMV MYTCSARHAA VNSGQLEYTS WMPNFPSSMR 600
    NPPMQTKGLT TLQTYMDTLP DVKTTCIVLL VLWTLCREPD DRRPLGHFPD 650
    IHFVEEGPRR SIEAFRQNLN QISHNIRQRN KCLTLPYYYL DPVLIENSIS 700
    I 701
    Length:701
    Mass (Da):80,578
    Last modified:August 1, 1998 - v1
    Checksum:iFAE3A3B8D2AA142E
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti9 – 91A → V in strain: C57BL/6 X SJL.
    Natural varianti351 – 3511M → V in strain: C57BL/6 X SJL.
    Natural varianti361 – 3611T → I in strain: C57BL/6 X SJL.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y14334 mRNA. Translation: CAA74714.1.
    AF059251 mRNA. Translation: AAC79681.1.
    CCDSiCCDS24885.1.
    RefSeqiNP_033789.1. NM_009659.2.
    UniGeneiMm.340329.

    Genome annotation databases

    EnsembliENSMUST00000036424; ENSMUSP00000035250; ENSMUSG00000032807.
    GeneIDi11686.
    KEGGimmu:11686.
    UCSCiuc007jpk.1. mouse.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Y14334 mRNA. Translation: CAA74714.1 .
    AF059251 mRNA. Translation: AAC79681.1 .
    CCDSi CCDS24885.1.
    RefSeqi NP_033789.1. NM_009659.2.
    UniGenei Mm.340329.

    3D structure databases

    ProteinModelPortali O70582.
    SMRi O70582. Positions 2-701.
    ModBasei Search...
    MobiDBi Search...

    PTM databases

    PhosphoSitei O70582.

    Proteomic databases

    PRIDEi O70582.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000036424 ; ENSMUSP00000035250 ; ENSMUSG00000032807 .
    GeneIDi 11686.
    KEGGi mmu:11686.
    UCSCi uc007jpk.1. mouse.

    Organism-specific databases

    CTDi 242.
    MGIi MGI:1274782. Alox12b.

    Phylogenomic databases

    eggNOGi NOG69653.
    HOGENOMi HOG000234358.
    HOVERGENi HBG005150.
    InParanoidi O70582.
    KOi K08021.
    OMAi YHFPAYQ.
    OrthoDBi EOG7V49XR.
    PhylomeDBi O70582.
    TreeFami TF105320.

    Enzyme and pathway databases

    UniPathwayi UPA00222 .
    UPA00881 .
    Reactomei REACT_196569. Synthesis of 12-eicosatetraenoic acid derivatives.

    Miscellaneous databases

    NextBioi 279327.
    PROi O70582.
    SOURCEi Search...

    Gene expression databases

    Bgeei O70582.
    CleanExi MM_ALOX12B.
    Genevestigatori O70582.

    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 of a 8-lipoxygenase and a novel epidermis-type lipoxygenase from phorbol ester-treated mouse skin."
      Krieg P., Kinzig A., Heidt M., Marks F., Fuerstenberger G.
      Biochim. Biophys. Acta 1391:7-12(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
      Strain: NMRI.
      Tissue: Epidermis.
    2. "Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignment."
      Sun D., McDonnell M., Chen X.-S., Lakkis M.M., Li H., Isaacs S.N., Elsea S.H., Patel P.I., Funk C.D.
      J. Biol. Chem. 273:33540-33547(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], DEVELOPMENTAL STAGE.
      Strain: C57BL/6 X SJL.
    3. "Sequence determinants for the reaction specificity of murine (12R)-lipoxygenase: targeted substrate modification and site-directed mutagenesis."
      Meruvu S., Walther M., Ivanov I., Hammarstroem S., Fuerstenberger G., Krieg P., Reddanna P., Kuhn H.
      J. Biol. Chem. 280:36633-36641(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ARACHIDONATE METABOLISM, CATALYTIC ACTIVITY, REACTION MECHANISM, PATHWAY, MUTAGENESIS OF PHE-390; GLY-441; ALA-455 AND VAL-631.
    4. Cited for: FUNCTION IN SKIN BARRIER, DISRUPTION PHENOTYPE.
    5. "A mouse mutation in the 12R-lipoxygenase, Alox12b, disrupts formation of the epidermal permeability barrier."
      Moran J.L., Qiu H., Turbe-Doan A., Yun Y., Boeglin W.E., Brash A.R., Beier D.R.
      J. Invest. Dermatol. 127:1893-1897(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN SKIN BARRIER, PATHWAY.
    6. "Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: a proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope."
      Zheng Y., Yin H., Boeglin W.E., Elias P.M., Crumrine D., Beier D.R., Brash A.R.
      J. Biol. Chem. 286:24046-24056(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN SKIN BARRIER, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiLX12B_MOUSE
    AccessioniPrimary (citable) accession number: O70582
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 11, 2001
    Last sequence update: August 1, 1998
    Last modified: October 1, 2014
    This is version 111 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Mummy, a recessive ethylnitrosurea-induced mutant has a nonsense mutation in the catalytic domain of Lox12b, resulting in truncation of the protein by 68 amino acids. The affected mice are born with red, shiny skin that dessicates and appears scaly. They probably die of dehydration like mice with targeted disruption of the gene (PubMed:17429434).1 Publication

    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