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Protein

Arachidonate 12-lipoxygenase, 12R-type

Gene

Alox12b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

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

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: hydroperoxy eicosatetraenoic acid biosynthesis

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 keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi398Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi403Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi578Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi582Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi701Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

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 functionDioxygenase, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandIron, Metal-binding

Enzyme and pathway databases

BRENDAi1.13.11.31 3474
ReactomeiR-MMU-2142712 Synthesis of 12-eicosatetraenoic acid derivatives
UniPathwayiUPA00222
UPA00881

Chemistry databases

SwissLipidsiSLP: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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1274782 Alox12b

Subcellular locationi

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)DescriptionActionsGraphical viewLength
Mutagenesisi390F → A: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi390F → W: Loss of enzymatic activity. 1 Publication1
Mutagenesisi441G → A: Reduced enzymatic activity and changed stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi441G → V: Loss of enzymatic activity. 1 Publication1
Mutagenesisi455A → I or W: Reduced enzymatic activity and altered stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi631V → A or G: Increased enzymatic activity and changed stereoselectivity of the oxygenation reaction to produce (11R)-HPETE preferentially instead of (12R)-HPETE. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206901 – 701Arachidonate 12-lipoxygenase, 12R-typeAdd BLAST701

Proteomic databases

PaxDbiO70582
PRIDEiO70582

PTM databases

PhosphoSitePlusiO70582

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

BgeeiENSMUSG00000032807
CleanExiMM_ALOX12B
ExpressionAtlasiO70582 baseline and differential
GenevisibleiO70582 MM

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000035250

Structurei

3D structure databases

ProteinModelPortaliO70582
SMRiO70582
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 119PLATPROSITE-ProRule annotationAdd BLAST118
Domaini120 – 701LipoxygenasePROSITE-ProRule annotationAdd BLAST582

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated

Phylogenomic databases

eggNOGiENOG410IF0U Eukaryota
ENOG410YN4N LUCA
GeneTreeiENSGT00550000074415
HOGENOMiHOG000234358
HOVERGENiHBG005150
InParanoidiO70582
KOiK08021
OMAiYHFPAYQ
OrthoDBiEOG091G04A4
PhylomeDBiO70582
TreeFamiTF105320

Family and domain databases

InterProiView 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
PANTHERiPTHR11771 PTHR11771, 1 hit
PfamiView protein in Pfam
PF00305 Lipoxygenase, 1 hit
PF01477 PLAT, 1 hit
PRINTSiPR00087 LIPOXYGENASE
PR00467 MAMLPOXGNASE
SMARTiView protein in SMART
SM00308 LH2, 1 hit
SUPFAMiSSF48484 SSF48484, 1 hit
SSF49723 SSF49723, 1 hit
PROSITEiView protein in PROSITE
PS00711 LIPOXYGENASE_1, 1 hit
PS00081 LIPOXYGENASE_2, 1 hit
PS51393 LIPOXYGENASE_3, 1 hit
PS50095 PLAT, 1 hit

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)DescriptionActionsGraphical viewLength
Natural varianti9A → V in strain: C57BL/6 X SJL. 1
Natural varianti351M → V in strain: C57BL/6 X SJL. 1
Natural varianti361T → 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
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

Similar proteinsi

Entry informationi

Entry nameiLX12B_MOUSE
AccessioniPrimary (citable) accession number: O70582
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: August 1, 1998
Last modified: March 28, 2018
This is version 133 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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