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Protein

Hydroperoxide isomerase ALOXE3

Gene

Aloxe3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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)DescriptionActionsGraphical viewLength
Metal bindingi408Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi413Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi588Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi592Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi711Iron; 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
  • 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

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-MMU-2142712 Synthesis of 12-eicosatetraenoic acid derivatives
UniPathwayiUPA00222
UPA00881

Chemistry databases

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1345140 Aloxe3

Subcellular locationi

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)DescriptionActionsGraphical viewLength
ChainiPRO_00002206921 – 711Hydroperoxide isomerase ALOXE3Add BLAST711

Proteomic databases

PaxDbiQ9WV07
PRIDEiQ9WV07

PTM databases

iPTMnetiQ9WV07
PhosphoSitePlusiQ9WV07

Expressioni

Tissue specificityi

Skin specific.

Gene expression databases

BgeeiENSMUSG00000020892
CleanExiMM_ALOXE3
ExpressionAtlasiQ9WV07 baseline and differential
GenevisibleiQ9WV07 MM

Interactioni

Protein-protein interaction databases

IntActiQ9WV07, 1 interactor
STRINGi10090.ENSMUSP00000021268

Structurei

3D structure databases

ProteinModelPortaliQ9WV07
SMRiQ9WV07
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 119PLATPROSITE-ProRule annotationAdd BLAST118
Domaini120 – 711LipoxygenasePROSITE-ProRule annotationAdd BLAST592

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated

Phylogenomic databases

eggNOGiENOG410IF0U Eukaryota
ENOG410YN4N LUCA
GeneTreeiENSGT00550000074415
HOGENOMiHOG000234358
HOVERGENiHBG005150
InParanoidiQ9WV07
KOiK18684
OMAiPVHCLNG
OrthoDBiEOG091G04A4
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.

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)DescriptionActionsGraphical viewLength
Sequence conflicti138Q → R in CAB46101 (PubMed:10366447).Curated1
Sequence conflicti341G → S in CAB46101 (PubMed:10366447).Curated1
Sequence conflicti591V → F in CAB46101 (PubMed:10366447).Curated1

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

Similar proteinsi

Entry informationi

Entry nameiLOXE3_MOUSE
AccessioniPrimary (citable) accession number: Q9WV07
Secondary accession number(s): B1ASX3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 27, 2003
Last sequence update: July 27, 2011
Last modified: March 28, 2018
This is version 119 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health