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Protein

Arachidonate 12-lipoxygenase, 12R-type

Gene

Alox12b

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. 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

Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation 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
  5. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: MGI

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
Complete GO annotation...

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
Complete GO annotation...

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.
ExpressionAtlasiO70582. baseline and differential.
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

        10         20         30         40         50
MATYKVKVAT GTDFFSGTLD SISLTIVGTQ GESHKQRLNH FGRDFATGAV
60 70 80 90 100
DDYTVQCQQD LGELIIIRLH KEPHSFLAKD PWYCNYVQIC APDCRVYHFP
110 120 130 140 150
AYQWMDGYET LALREATGKI TADDTLPILL EHRQEEIRAK KDFYHWRVFV
160 170 180 190 200
PGLPNYVDIP SYHPPPRRCR NPNRPEWDGY IPGFPILINI KATRFLNSNL
210 220 230 240 250
RFSFVKTASF FYRLGPMALA FKLRGLVDRK RSWKRLKDIK NIFPATKSVV
260 270 280 290 300
SEYVAEHWTE DSFFGYQYLN GINPGLIRRC TQIPDKFPVT DEMVAPFLGE
310 320 330 340 350
GTCLQAELER GNIYLADYRI LDGIPTVELN GQQQHHCAPM CLLHFGPDGN
360 370 380 390 400
MMPIAIQLSQ TPGPDCPIFL PNDSEWDWLL AKTWVRYAEF YSHEAVAHLL
410 420 430 440 450
ESHLIGEAFC LALLRNLPMC HPLYKLLIPH TRYNVQINSI GRALLLNKGG
460 470 480 490 500
LSARAMSLGL EGFAQVMVRG LSELTYKSLC IPNDFVERGV QDLPGYYFRD
510 520 530 540 550
DSLAVWYAME RYVTEIITYY YPNDAAVEGD PELQCWVQEI FKECLLGRES
560 570 580 590 600
SGFPTCLRTI PELIEYVTMV MYTCSARHAA VNSGQLEYTS WMPNFPSSMR
610 620 630 640 650
NPPMQTKGLT TLQTYMDTLP DVKTTCIVLL VLWTLCREPD DRRPLGHFPD
660 670 680 690 700
IHFVEEGPRR SIEAFRQNLN QISHNIRQRN KCLTLPYYYL DPVLIENSIS

I
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
Links Updated
Y14334 mRNA. Translation: CAA74714.1.
AF059251 mRNA. Translation: AAC79681.1.
CCDSiCCDS24885.1.
RefSeqiNP_033789.1. NM_009659.2.
UniGeneiMm.340329.

3D structure databases

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

PTM databases

PhosphoSiteiO70582.

Proteomic databases

PRIDEiO70582.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi242.
MGIiMGI:1274782. Alox12b.

Phylogenomic databases

eggNOGiNOG69653.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiO70582.
KOiK08021.
OMAiYHFPAYQ.
OrthoDBiEOG7V49XR.
PhylomeDBiO70582.
TreeFamiTF105320.

Enzyme and pathway databases

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

Miscellaneous databases

NextBioi279327.
PROiO70582.
SOURCEiSearch...

Gene expression databases

BgeeiO70582.
CleanExiMM_ALOX12B.
ExpressionAtlasiO70582. baseline and differential.
GenevestigatoriO70582.

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]
ProtoNetiSearch...

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: February 4, 2015
This is version 115 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

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 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.