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Protein

Hydroperoxide isomerase ALOXE3

Gene

Aloxe3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols. The dioxygenase activity requires a step of activation of the enzyme by molecular oxygen. In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides. In the skin, acts downstream of ALOX12B on the linoleate 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. In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites. Plays also a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG. Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia.3 Publications

Catalytic activityi

A hydroperoxy icosatetraenoate = a hydroxy epoxy icosatrienoate.1 Publication
A hydroperoxy icosatetraenoate = an oxoicosatetraenoate + H2O.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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi408 – 4081Iron; catalyticPROSITE-ProRule annotation
Metal bindingi413 – 4131Iron; catalyticPROSITE-ProRule annotation
Metal bindingi588 – 5881Iron; catalyticPROSITE-ProRule annotation
Metal bindingi592 – 5921Iron; catalyticPROSITE-ProRule annotation
Metal bindingi711 – 7111Iron; via carboxylate; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

  • arachidonic acid metabolic process Source: UniProtKB
  • ceramide biosynthetic process Source: UniProtKB
  • establishment of skin barrier Source: UniProtKB
  • fat cell differentiation Source: UniProtKB
  • hepoxilin biosynthetic process Source: UniProtKB
  • linoleic acid metabolic process Source: UniProtKB
  • lipoxygenase pathway Source: UniProtKB
  • peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
  • sensory perception of pain Source: UniProtKB
  • sphingolipid metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Isomerase, Lyase, Oxidoreductase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

UniPathwayiUPA00222.
UPA00881.

Chemistry

SwissLipidsiSLP:000000661.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroperoxide isomerase ALOXE3 (EC:5.4.4.71 Publication)
Alternative name(s):
Epidermis-type lipoxygenase 31 Publication
Short name:
Epidermal LOX-3
Short name:
e-LOX-3
Short name:
eLOX-3
Hydroperoxy icosatetraenoate dehydratase (EC:4.2.1.1521 Publication)
Gene namesi
Name:Aloxe3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1345140. Aloxe3.

Subcellular locationi

  • Cytoplasm PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

Mice die within 5 to 12 hours after birth due to defective skin barrier function loosing around 2.5% of body weight per hour. Dehydratation through the skin is increased 4 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. Hyperkeratosis of the skin is observed but it is not associated with defects in epidermal differentiation while the ceramide composition of the epidermis is altered with an absence of ester-bound ceramides.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 711711Hydroperoxide isomerase ALOXE3PRO_0000220692Add
BLAST

Proteomic databases

PaxDbiQ9WV07.
PRIDEiQ9WV07.

PTM databases

PhosphoSiteiQ9WV07.

Expressioni

Tissue specificityi

Skin specific.

Gene expression databases

BgeeiQ9WV07.
CleanExiMM_ALOXE3.
ExpressionAtlasiQ9WV07. baseline and differential.
GenevisibleiQ9WV07. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021268.

Structurei

3D structure databases

ProteinModelPortaliQ9WV07.
SMRiQ9WV07. Positions 2-711.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 119118PLATPROSITE-ProRule annotationAdd
BLAST
Domaini120 – 711592LipoxygenasePROSITE-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

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiQ9WV07.
KOiK18684.
OMAiCSRICVT.
OrthoDBiEOG7V49XR.
TreeFamiTF105320.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. 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.

Q9WV07-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVYRLCVTT GSYLKAGTLD NIYATLVGTC GESPKQKLDR VGRDFASGSV
60 70 80 90 100
QKYKVRCEAE LGEILLLRLH KERFAFFCKD PWYCSRICVT APDGSAVHFP
110 120 130 140 150
CYQWIDGYCT VELRPGTART ICQDSLPLLL DHRKRELQAR QECYRWKIFA
160 170 180 190 200
PGFPRMVDVS SFQEMESDKK FALTKTVPCA EQDDNSGNRY LPGFPMKIDI
210 220 230 240 250
PSLLHMEPNI RYSATKTASL IFNALPASFG MKIRGLLDRK GSWKRLDDIR
260 270 280 290 300
NIFWCHKTFT SEYVTEHWCE DSFFGYQYLN GVNPVMLHCL SSLPSKLPVT
310 320 330 340 350
NDMVAPLLGP GTCLQTELER GHIFLADYWI LAEAPVHCIN GLQQYVTAPL
360 370 380 390 400
CLLWLNPQGV LLPLAIQLSQ TPGPESPIFL PTDCELDWLL AKTWVRNSEF
410 420 430 440 450
LVHENNTHFL CTHLLCEAFS MATLRQLPLC HPVYKLLLPH TRYTLQVNTI
460 470 480 490 500
ARATLLNPDG LVDKVTSIGR QGLIYLMSTG LAHFTYTDFC LPDSIRARGV
510 520 530 540 550
LTIPNYHYRD DGLKIWAAIE RFVSEIVSYY YPSDASVQQD CELQAWVGEI
560 570 580 590 600
FAQAFLGRES SGFPSRLCTP GELVKYLTAI IFNCSAQHAA VNSGQHDFGA
610 620 630 640 650
WMPNAPSSMR QPPPQTKGDT TMKSYLDTLP EVNTTCRNLL LFWLVSQEPK
660 670 680 690 700
DQRPLGTYPD EHFTEEAPRQ SIAAFQNCLA QISKDIRERN QSLALPYAYL
710
DPPLIENSVS I
Length:711
Mass (Da):80,473
Last modified:July 27, 2011 - v2
Checksum:i85A75EE2AFF3000E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti138 – 1381Q → R in CAB46101 (PubMed:10366447).Curated
Sequence conflicti341 – 3411G → S in CAB46101 (PubMed:10366447).Curated
Sequence conflicti591 – 5911V → F in CAB46101 (PubMed:10366447).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y14695 mRNA. Translation: CAB46101.1.
AL645527 Genomic DNA. Translation: CAI35248.1.
CH466601 Genomic DNA. Translation: EDL10481.1.
CCDSiCCDS24884.1.
RefSeqiNP_035916.2. NM_011786.2.
UniGeneiMm.41989.

Genome annotation databases

EnsembliENSMUST00000021268; ENSMUSP00000021268; ENSMUSG00000020892.
GeneIDi23801.
KEGGimmu:23801.
UCSCiuc007jpj.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y14695 mRNA. Translation: CAB46101.1.
AL645527 Genomic DNA. Translation: CAI35248.1.
CH466601 Genomic DNA. Translation: EDL10481.1.
CCDSiCCDS24884.1.
RefSeqiNP_035916.2. NM_011786.2.
UniGeneiMm.41989.

3D structure databases

ProteinModelPortaliQ9WV07.
SMRiQ9WV07. Positions 2-711.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000021268.

Chemistry

SwissLipidsiSLP:000000661.

PTM databases

PhosphoSiteiQ9WV07.

Proteomic databases

PaxDbiQ9WV07.
PRIDEiQ9WV07.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021268; ENSMUSP00000021268; ENSMUSG00000020892.
GeneIDi23801.
KEGGimmu:23801.
UCSCiuc007jpj.2. mouse.

Organism-specific databases

CTDi59344.
MGIiMGI:1345140. Aloxe3.

Phylogenomic databases

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiQ9WV07.
KOiK18684.
OMAiCSRICVT.
OrthoDBiEOG7V49XR.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00222.
UPA00881.

Miscellaneous databases

NextBioi303419.
PROiQ9WV07.
SOURCEiSearch...

Gene expression databases

BgeeiQ9WV07.
CleanExiMM_ALOXE3.
ExpressionAtlasiQ9WV07. baseline and differential.
GenevisibleiQ9WV07. MM.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. 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

« Hide 'large scale' publications
  1. "cDNA cloning, genomic structure and chromosomal localization of a novel epidermis-type lipoxygenase."
    Kinzig A., Heidt M., Fuerstenberger G., Marks F., Krieg P.
    Genomics 58:158-164(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: NMRI.
    Tissue: Skin.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Human and mouse eLOX3 have distinct substrate specificities: implications for their linkage with lipoxygenases in skin."
    Yu Z., Schneider C., Boeglin W.E., Brash A.R.
    Arch. Biochem. Biophys. 455:188-196(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A HYDROPEROXIDE ISOMERASE, CATALYTIC ACTIVITY.
  5. "Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity."
    Hallenborg P., Joergensen C., Petersen R.K., Feddersen S., Araujo P., Markt P., Langer T., Furstenberger G., Krieg P., Koppen A., Kalkhoven E., Madsen L., Kristiansen K.
    Mol. Cell. Biol. 30:4077-4091(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PPARG ACTIVATION.
  6. "Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation."
    Krieg P., Rosenberger S., de Juanes S., Latzko S., Hou J., Dick A., Kloz U., van der Hoeven F., Hausser I., Esposito I., Rauh M., Schneider H.
    J. Invest. Dermatol. 133:172-180(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN SKIN BARRIER, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiLOXE3_MOUSE
AccessioniPrimary (citable) accession number: Q9WV07
Secondary accession number(s): B1ASX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 27, 2003
Last sequence update: July 27, 2011
Last modified: January 20, 2016
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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

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 one 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.