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O70582 (LX12B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Arachidonate 12-lipoxygenase, 12R-type

Short name=12R-LOX
Short name=12R-lipoxygenase
EC=1.13.11.-
Alternative name(s):
Epidermis-type lipoxygenase 12
Epidermis-type lipoxygenase 2
Short name=e-LOX 2
Gene names
Name:Alox12b
Synonyms:Aloxe2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length701 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.3 Ref.4 Ref.5 Ref.6

Catalytic activity

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12R)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. Ref.3

Cofactor

Binds 1 iron ion per subunit By similarity.

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. Ref.3 Ref.5

Lipid metabolism; sphingolipid metabolism. Ref.3 Ref.5

Subcellular location

Cytoplasm By similarity.

Tissue specificity

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. Ref.1

Developmental stage

In the embryo, expression begins at day 15.5. Ref.2

Disruption phenotype

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. Ref.4 Ref.6

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 (Ref.5).

Sequence similarities

Belongs to the lipoxygenase family.

Contains 1 lipoxygenase domain.

Contains 1 PLAT domain.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Inferred from direct assay Ref.3. Source: UniProtKB

ceramide biosynthetic process

Inferred from mutant phenotype Ref.4. Source: UniProtKB

establishment of skin barrier

Inferred from mutant phenotype Ref.4Ref.6. Source: UniProtKB

hepoxilin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

linoleic acid metabolic process

Inferred from direct assay Ref.3. Source: UniProtKB

lipoxygenase pathway

Inferred from sequence or structural similarity. Source: UniProtKB

oxidation-reduction process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of MAPK cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of mucus secretion

Inferred from sequence or structural similarity. Source: UniProtKB

protein lipidation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

sphingolipid metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionarachidonate 12-lipoxygenase activity

Inferred from direct assay Ref.3. Source: UniProtKB

catalytic activity

Inferred from direct assay PubMed 10366447. Source: MGI

iron ion binding

Inferred from electronic annotation. Source: InterPro

linoleate 9S-lipoxygenase activity

Inferred from direct assay Ref.3. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 701701Arachidonate 12-lipoxygenase, 12R-type
PRO_0000220690

Regions

Domain2 – 119118PLAT
Domain120 – 701582Lipoxygenase

Sites

Metal binding3981Iron; catalytic By similarity
Metal binding4031Iron; catalytic By similarity
Metal binding5781Iron; catalytic By similarity
Metal binding5821Iron; catalytic By similarity
Metal binding7011Iron; via carboxylate; catalytic By similarity

Natural variations

Natural variant91A → V in strain: C57BL/6 X SJL.
Natural variant3511M → V in strain: C57BL/6 X SJL.
Natural variant3611T → I in strain: C57BL/6 X SJL.

Experimental info

Mutagenesis3901F → A: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. Ref.3
Mutagenesis3901F → W: Loss of enzymatic activity. Ref.3
Mutagenesis4411G → A: Reduced enzymatic activity and changed stereoselectivity of the oxygenation reaction. Ref.3
Mutagenesis4411G → V: Loss of enzymatic activity. Ref.3
Mutagenesis4551A → I or W: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. Ref.3
Mutagenesis6311V → A or G: Increased enzymatic activity and changed stereoselectivity of the oxygenation reaction to produce (11R)-HPETE preferentially instead of (12R)-HPETE. Ref.3

Sequences

Sequence LengthMass (Da)Tools
O70582 [UniParc].

Last modified August 1, 1998. Version 1.
Checksum: FAE3A3B8D2AA142E

FASTA70180,578
        10         20         30         40         50         60 
MATYKVKVAT GTDFFSGTLD SISLTIVGTQ GESHKQRLNH FGRDFATGAV DDYTVQCQQD 

        70         80         90        100        110        120 
LGELIIIRLH KEPHSFLAKD PWYCNYVQIC APDCRVYHFP AYQWMDGYET LALREATGKI 

       130        140        150        160        170        180 
TADDTLPILL EHRQEEIRAK KDFYHWRVFV PGLPNYVDIP SYHPPPRRCR NPNRPEWDGY 

       190        200        210        220        230        240 
IPGFPILINI KATRFLNSNL RFSFVKTASF FYRLGPMALA FKLRGLVDRK RSWKRLKDIK 

       250        260        270        280        290        300 
NIFPATKSVV SEYVAEHWTE DSFFGYQYLN GINPGLIRRC TQIPDKFPVT DEMVAPFLGE 

       310        320        330        340        350        360 
GTCLQAELER GNIYLADYRI LDGIPTVELN GQQQHHCAPM CLLHFGPDGN MMPIAIQLSQ 

       370        380        390        400        410        420 
TPGPDCPIFL PNDSEWDWLL AKTWVRYAEF YSHEAVAHLL ESHLIGEAFC LALLRNLPMC 

       430        440        450        460        470        480 
HPLYKLLIPH TRYNVQINSI GRALLLNKGG LSARAMSLGL EGFAQVMVRG LSELTYKSLC 

       490        500        510        520        530        540 
IPNDFVERGV QDLPGYYFRD DSLAVWYAME RYVTEIITYY YPNDAAVEGD PELQCWVQEI 

       550        560        570        580        590        600 
FKECLLGRES SGFPTCLRTI PELIEYVTMV MYTCSARHAA VNSGQLEYTS WMPNFPSSMR 

       610        620        630        640        650        660 
NPPMQTKGLT TLQTYMDTLP DVKTTCIVLL VLWTLCREPD DRRPLGHFPD IHFVEEGPRR 

       670        680        690        700 
SIEAFRQNLN QISHNIRQRN KCLTLPYYYL DPVLIENSIS I 

« Hide

References

[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]"12R-lipoxygenase deficiency disrupts epidermal barrier function."
Epp N., Fuerstenberger G., Mueller K., de Juanes S., Leitges M., Hausser I., Thieme F., Liebisch G., Schmitz G., Krieg P.
J. Cell Biol. 177:173-182(2007) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y14334 mRNA. Translation: CAA74714.1.
AF059251 mRNA. Translation: AAC79681.1.
CCDSCCDS24885.1.
RefSeqNP_033789.1. NM_009659.2.
UniGeneMm.340329.

3D structure databases

ProteinModelPortalO70582.
SMRO70582. Positions 2-701.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteO70582.

Proteomic databases

PRIDEO70582.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000036424; ENSMUSP00000035250; ENSMUSG00000032807.
GeneID11686.
KEGGmmu:11686.
UCSCuc007jpk.1. mouse.

Organism-specific databases

CTD242.
MGIMGI:1274782. Alox12b.

Phylogenomic databases

eggNOGNOG69653.
HOGENOMHOG000234358.
HOVERGENHBG005150.
InParanoidO70582.
KOK08021.
OMAYHFPAYQ.
OrthoDBEOG7V49XR.
PhylomeDBO70582.
TreeFamTF105320.

Enzyme and pathway databases

UniPathwayUPA00222.
UPA00881.

Gene expression databases

BgeeO70582.
CleanExMM_ALOX12B.
GenevestigatorO70582.

Family and domain databases

Gene3D2.60.60.20. 1 hit.
InterProIPR008976. Lipase_LipOase.
IPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERPTHR11771. PTHR11771. 1 hit.
PfamPF00305. Lipoxygenase. 1 hit.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio279327.
PROO70582.
SOURCESearch...

Entry information

Entry nameLX12B_MOUSE
AccessionPrimary (citable) accession number: O70582
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: August 1, 1998
Last modified: July 9, 2014
This is version 109 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot