Hmdb loader
Identification
HMDB Protein ID HMDBP13376
Secondary Accession Numbers None
Name Arachidonate 12-lipoxygenase, 12R-type
Synonyms
  1. 12R-LOX
  2. 12R-lipoxygenase
  3. Epidermis-type lipoxygenase 12
  4. Epidermis-type lipoxygenase 2
  5. e-LOX 2
Gene Name ALOX12B
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Catalyzes the regio and stereo-specific incorporation of a single molecule of dioxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:16129665). Does not convert arachidonic acid to (12R)-hydroperoxyeicosatetraenoic acid/(12R)-HPETE (PubMed:10100631, PubMed:11256953). 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 (PubMed:17403930, PubMed:17429434, PubMed:21558561). May also play a role in the regulation of the expression of airway mucins (By similarity).
Pathways
  • Arachidonic acid metabolism
  • hydroperoxy eicosatetraenoic acid biosynthesis
  • Serotonergic synapse
  • sphingolipid metabolism
Reactions Not Available
GO Classification
Biological Process
protein lipidation
positive regulation of mucus secretion
linoleic acid metabolic process
positive regulation of gene expression
establishment of skin barrier
positive regulation of MAPK cascade
sphingolipid metabolic process
ceramide biosynthetic process
arachidonic acid metabolic process
hepoxilin biosynthetic process
lipoxygenase pathway
lipid oxidation
Cellular Component
perinuclear region of cytoplasm
cytosol
Molecular Function
linoleate 9S-lipoxygenase activity
arachidonate 12-lipoxygenase activity
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
arachidonate 8(R)-lipoxygenase activity
catalytic activity
iron ion binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 701
Molecular Weight 80576.82
Theoretical pI 6.709
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O70582
UniProtKB/Swiss-Prot Entry Name LX12B_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Sun D, McDonnell M, Chen XS, Lakkis MM, Li H, Isaacs SN, Elsea SH, Patel PI, Funk CD: Human 12(R)-lipoxygenase and the mouse ortholog. Molecular cloning, expression, and gene chromosomal assignment. J Biol Chem. 1998 Dec 11;273(50):33540-7. [PubMed:9837935 ]
  2. Krieg P, Kinzig A, Heidt M, Marks F, Furstenberger G: cDNA cloning of a 8-lipoxygenase and a novel epidermis-type lipoxygenase from phorbol ester-treated mouse skin. Biochim Biophys Acta. 1998 Mar 6;1391(1):7-12. doi: 10.1016/s0005-2760(97)00214-2. [PubMed:9518531 ]
  3. Krieg P, Siebert M, Kinzig A, Bettenhausen R, Marks F, Furstenberger G: Murine 12(R)-lipoxygenase: functional expression, genomic structure and chromosomal localization. FEBS Lett. 1999 Mar 5;446(1):142-8. doi: 10.1016/s0014-5793(99)00196-9. [PubMed:10100631 ]
  4. Siebert M, Krieg P, Lehmann WD, Marks F, Furstenberger G: Enzymic characterization of epidermis-derived 12-lipoxygenase isoenzymes. Biochem J. 2001 Apr 1;355(Pt 1):97-104. doi: 10.1042/0264-6021:3550097. [PubMed:11256953 ]
  5. Meruvu S, Walther M, Ivanov I, Hammarstrom S, Furstenberger G, Krieg P, Reddanna P, Kuhn H: Sequence determinants for the reaction specificity of murine (12R)-lipoxygenase: targeted substrate modification and site-directed mutagenesis. J Biol Chem. 2005 Nov 4;280(44):36633-41. doi: 10.1074/jbc.M508260200. Epub 2005 Aug 29. [PubMed:16129665 ]
  6. Epp N, Furstenberger G, Muller K, de Juanes S, Leitges M, Hausser I, Thieme F, Liebisch G, Schmitz G, Krieg P: 12R-lipoxygenase deficiency disrupts epidermal barrier function. J Cell Biol. 2007 Apr 9;177(1):173-82. doi: 10.1083/jcb.200612116. Epub 2007 Apr 2. [PubMed:17403930 ]
  7. Zheng Y, Yin H, Boeglin WE, Elias PM, Crumrine D, Beier DR, Brash AR: 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. J Biol Chem. 2011 Jul 8;286(27):24046-56. doi: 10.1074/jbc.M111.251496. Epub 2011 May 10. [PubMed:21558561 ]