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Protein

Hydroperoxide isomerase ALOXE3

Gene

Aloxe3

Organism
Rattus norvegicus (Rat)
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 activates PPARG. Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia.1 Publication

Catalytic activityi

A hydroperoxy icosatetraenoate = a hydroxy epoxy icosatrienoate.
A hydroperoxy icosatetraenoate = an oxoicosatetraenoate + H2O.

Cofactori

Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation

Pathwayi

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

  1. hepoxilin A3 synthase activity Source: UniProtKB
  2. iron ion binding Source: InterPro
  3. lyase activity Source: UniProtKB-KW
  4. oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: UniProtKB

GO - Biological processi

  1. arachidonic acid metabolic process Source: UniProtKB
  2. ceramide biosynthetic process Source: UniProtKB
  3. establishment of skin barrier Source: UniProtKB
  4. fat cell differentiation Source: UniProtKB
  5. hepoxilin biosynthetic process Source: UniProtKB
  6. linoleic acid metabolic process Source: UniProtKB
  7. lipoxygenase pathway Source: UniProtKB
  8. peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
  9. sensory perception of pain Source: UniProtKB
  10. 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.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroperoxide isomerase ALOXE3 (EC:5.4.4.7)
Alternative name(s):
Epidermis-type lipoxygenase 3
Short name:
Epidermal LOX-3
Short name:
e-LOX-3
Short name:
eLOX-3
Hydroperoxy icosatetraenoate dehydratase (EC:4.2.1.152)
Gene namesi
Name:Aloxe3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 10

Organism-specific databases

RGDi1306252. Aloxe3.

Subcellular locationi

Cytoplasm PROSITE-ProRule annotation

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 711711Hydroperoxide isomerase ALOXE3PRO_0000423419Add
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 119118PLATPROSITE-ProRule annotationAdd
BLAST
Domaini119 – 711593LipoxygenasePROSITE-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

GeneTreeiENSGT00550000074415.
InParanoidiD3ZKX9.
KOiK18684.
OMAiCSRICVT.
OrthoDBiEOG7V49XR.
PhylomeDBiD3ZKX9.
TreeFamiTF105320.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR008976. Lipase_LipOase.
IPR000907. 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.

D3ZKX9-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MAVYRLCVTT GSYLKAGTLD NIYATLVGTC GESPKQKLDR VGRDFATGSV
60 70 80 90 100
QKYKVRCASE LGEILLLRLH KERFAFFCKD PWYCSRICVT TPDGSVVHFP
110 120 130 140 150
CYQWIDGYCT VELRPGTART ICQDALPLLL DHRKRELQAR QECYRWKIYA
160 170 180 190 200
PGFPRMVDVS SFEEMESDKK FALTKTAPCA DQDDNSGNRY LPGFPMKVDI
210 220 230 240 250
PSLLHMEPNI RYSATKTASL IFNALPASLG MKIRGLLDRK GSWKRLDDIR
260 270 280 290 300
NIFWCHKTFT SEYVTEHWCE DSFFGYQYLN GVNPIMLHCL SSLPSKLPVT
310 320 330 340 350
NDMVAPLLGP GTCLQTELER GHIFLADYWI LAEAPVHCLN GRQQYVTAPL
360 370 380 390 400
CLLWLNPQGV LLPLAIQLSQ IPGPESPIFL PTDCELDWLL AKTWVRNSEF
410 420 430 440 450
LVHENNTHFL CTHLLCEAFS MATLRQLPLC HPVYKLLLPH TRYTLQVNTI
460 470 480 490 500
ARATLLNPDG LVDKVTSIGR RGLIYLMSTG LAHFTYTDFC LPDSLRARGV
510 520 530 540 550
LTIPNYHYRD DGLKIWAAIE RFVSEIVSYY YPNDACVQQD SELQAWVGEI
560 570 580 590 600
FAQAFLGRES SGFPSRLCTP GELVKYLTAI IFNCSAQHAA VNSGQHDFGA
610 620 630 640 650
WMPNAPSSMR QPPPQTKGNT TMESYLETLP EVNTTCSNLL LFWLVSQEPK
660 670 680 690 700
DQRPLGTYPD EHFTEEAPRQ SIAAFQKCLA QISKDIRARN ESLALPYAYL
710
DPPLIENSVS I
Length:711
Mass (Da):80,440
Last modified:April 20, 2010 - v1
Checksum:i41C3D9BBC6C4532B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06064371 Genomic DNA. No translation available.
CH473948 Genomic DNA. Translation: EDM04845.1.
RefSeqiNP_001099263.1. NM_001105793.1.
XP_006246679.1. XM_006246617.2.
UniGeneiRn.8716.

Genome annotation databases

EnsembliENSRNOT00000010141; ENSRNOP00000010141; ENSRNOG00000007454.
GeneIDi287424.
KEGGirno:287424.
UCSCiRGD:1306252. rat.

Cross-referencesi

Web resourcesi

Protein Spotlight

about water - Issue 153 of September 2013

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06064371 Genomic DNA. No translation available.
CH473948 Genomic DNA. Translation: EDM04845.1.
RefSeqiNP_001099263.1. NM_001105793.1.
XP_006246679.1. XM_006246617.2.
UniGeneiRn.8716.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000010141; ENSRNOP00000010141; ENSRNOG00000007454.
GeneIDi287424.
KEGGirno:287424.
UCSCiRGD:1306252. rat.

Organism-specific databases

CTDi59344.
RGDi1306252. Aloxe3.

Phylogenomic databases

GeneTreeiENSGT00550000074415.
InParanoidiD3ZKX9.
KOiK18684.
OMAiCSRICVT.
OrthoDBiEOG7V49XR.
PhylomeDBiD3ZKX9.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00222.
UPA00881.

Miscellaneous databases

NextBioi626099.
PROiD3ZKX9.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR008976. Lipase_LipOase.
IPR000907. 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. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. 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].
    Strain: Brown Norway.
  3. "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia."
    Gregus A.M., Dumlao D.S., Wei S.C., Norris P.C., Catella L.C., Meyerstein F.G., Buczynski M.W., Steinauer J.J., Fitzsimmons B.L., Yaksh T.L., Dennis E.A.
    FASEB J. 27:1939-1949(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN ALGESIA.

Entry informationi

Entry nameiLOXE3_RAT
AccessioniPrimary (citable) accession number: D3ZKX9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 18, 2013
Last sequence update: April 20, 2010
Last modified: January 7, 2015
This is version 39 of the entry and version 1 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.