UniProtKB - O70582 (LX12B_MOUSE)
Protein
Arachidonate 12-lipoxygenase, 12R-type
Gene
Alox12b
Organism
Mus musculus (Mouse)
Status
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
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
Catalytic activityi
Cofactori
Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation
: hydroperoxy eicosatetraenoic acid biosynthesis Pathwayi
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.
Pathwayi: sphingolipid metabolism
This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.View all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 398 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 403 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 578 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 582 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 701 | Iron; via carboxylate; catalyticPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- arachidonate 12-lipoxygenase activity Source: UniProtKB
- catalytic activity Source: MGI
- iron ion binding Source: InterPro
- linoleate 9S-lipoxygenase activity Source: UniProtKB
- oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: MGI
GO - Biological processi
- arachidonic acid metabolic process Source: UniProtKB
- ceramide biosynthetic process Source: UniProtKB
- establishment of skin barrier Source: UniProtKB
- hepoxilin biosynthetic process Source: UniProtKB
- linoleic acid metabolic process Source: UniProtKB
- lipoxygenase pathway Source: UniProtKB
- oxidation-reduction process Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of MAPK cascade Source: UniProtKB
- positive regulation of mucus secretion Source: UniProtKB
- protein lipidation Source: UniProtKB
- sphingolipid metabolic process Source: UniProtKB
Keywordsi
Molecular function | Dioxygenase, Oxidoreductase |
Biological process | Fatty acid metabolism, Lipid metabolism |
Ligand | Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 1.13.11.31 3474 |
Reactomei | R-MMU-2142712 Synthesis of 12-eicosatetraenoic acid derivatives |
UniPathwayi | UPA00222 UPA00881 |
Chemistry databases
SwissLipidsi | SLP:000000658 SLP:000000942 |
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 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1274782 Alox12b |
Subcellular locationi
Keywords - Cellular componenti
CytoplasmPathology & 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 18.5 dpc 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 390 | F → A: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication | 1 | |
Mutagenesisi | 390 | F → W: Loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 441 | G → A: Reduced enzymatic activity and changed stereoselectivity of the oxygenation reaction. 1 Publication | 1 | |
Mutagenesisi | 441 | G → V: Loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 455 | A → I or W: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication | 1 | |
Mutagenesisi | 631 | V → A or G: Increased enzymatic activity and changed stereoselectivity of the oxygenation reaction to produce (11R)-HPETE preferentially instead of (12R)-HPETE. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220690 | 1 – 701 | Arachidonate 12-lipoxygenase, 12R-typeAdd BLAST | 701 |
Proteomic databases
PaxDbi | O70582 |
PRIDEi | O70582 |
PTM databases
PhosphoSitePlusi | O70582 |
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
Bgeei | ENSMUSG00000032807 Expressed in 42 organ(s), highest expression level in esophagus |
ExpressionAtlasi | O70582 baseline and differential |
Genevisiblei | O70582 MM |
Structurei
3D structure databases
ProteinModelPortali | O70582 |
SMRi | O70582 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2 – 119 | PLATPROSITE-ProRule annotationAdd BLAST | 118 | |
Domaini | 120 – 701 | LipoxygenasePROSITE-ProRule annotationAdd BLAST | 582 |
Sequence similaritiesi
Belongs to the lipoxygenase family.Curated
Phylogenomic databases
eggNOGi | ENOG410IF0U Eukaryota ENOG410YN4N LUCA |
GeneTreei | ENSGT00940000162032 |
HOGENOMi | HOG000234358 |
HOVERGENi | HBG005150 |
InParanoidi | O70582 |
KOi | K08021 |
OMAi | TQGESHK |
OrthoDBi | 385042at2759 |
PhylomeDBi | O70582 |
TreeFami | TF105320 |
Family and domain databases
InterProi | View 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 |
PANTHERi | PTHR11771 PTHR11771, 1 hit |
Pfami | View protein in Pfam PF00305 Lipoxygenase, 1 hit PF01477 PLAT, 1 hit |
PRINTSi | PR00087 LIPOXYGENASE PR00467 MAMLPOXGNASE |
SMARTi | View protein in SMART SM00308 LH2, 1 hit |
SUPFAMi | SSF48484 SSF48484, 1 hit SSF49723 SSF49723, 1 hit |
PROSITEi | View protein in PROSITE PS00711 LIPOXYGENASE_1, 1 hit PS00081 LIPOXYGENASE_2, 1 hit PS51393 LIPOXYGENASE_3, 1 hit PS50095 PLAT, 1 hit |
i Sequence
Sequence statusi: Complete.
O70582-1 [UniParc]FASTAAdd to basket
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 9 | A → V in strain: C57BL/6 X SJL. | 1 | |
Natural varianti | 351 | M → V in strain: C57BL/6 X SJL. | 1 | |
Natural varianti | 361 | T → I in strain: C57BL/6 X SJL. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi 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 |
Genome annotation databases
Ensembli | ENSMUST00000036424; ENSMUSP00000035250; ENSMUSG00000032807 |
GeneIDi | 11686 |
KEGGi | mmu:11686 |
UCSCi | uc007jpk.1 mouse |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi 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 |
ModBasei | Search... |
MobiDBi | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000035250 |
Chemistry databases
SwissLipidsi | SLP:000000658 SLP:000000942 |
PTM databases
PhosphoSitePlusi | O70582 |
Proteomic databases
PaxDbi | O70582 |
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 | ENOG410IF0U Eukaryota ENOG410YN4N LUCA |
GeneTreei | ENSGT00940000162032 |
HOGENOMi | HOG000234358 |
HOVERGENi | HBG005150 |
InParanoidi | O70582 |
KOi | K08021 |
OMAi | TQGESHK |
OrthoDBi | 385042at2759 |
PhylomeDBi | O70582 |
TreeFami | TF105320 |
Enzyme and pathway databases
UniPathwayi | UPA00222 UPA00881 |
BRENDAi | 1.13.11.31 3474 |
Reactomei | R-MMU-2142712 Synthesis of 12-eicosatetraenoic acid derivatives |
Miscellaneous databases
PROi | PR:O70582 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000032807 Expressed in 42 organ(s), highest expression level in esophagus |
ExpressionAtlasi | O70582 baseline and differential |
Genevisiblei | O70582 MM |
Family and domain databases
InterProi | View 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 |
PANTHERi | PTHR11771 PTHR11771, 1 hit |
Pfami | View protein in Pfam PF00305 Lipoxygenase, 1 hit PF01477 PLAT, 1 hit |
PRINTSi | PR00087 LIPOXYGENASE PR00467 MAMLPOXGNASE |
SMARTi | View protein in SMART SM00308 LH2, 1 hit |
SUPFAMi | SSF48484 SSF48484, 1 hit SSF49723 SSF49723, 1 hit |
PROSITEi | View protein in PROSITE PS00711 LIPOXYGENASE_1, 1 hit PS00081 LIPOXYGENASE_2, 1 hit PS51393 LIPOXYGENASE_3, 1 hit PS50095 PLAT, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | LX12B_MOUSE | |
Accessioni | O70582Primary (citable) accession number: O70582 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 11, 2001 |
Last sequence update: | August 1, 1998 | |
Last modified: | February 13, 2019 | |
This is version 138 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways