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Q02759 (LOX15_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Arachidonate 15-lipoxygenase

Short name=15-LOX
EC=1.13.11.33
Alternative name(s):
12/15-lipoxygenase
Arachidonate 12-lipoxygenase, leukocyte-type
Short name=12-LOX
EC=1.13.11.31
Arachidonate omega-6 lipoxygenase
Gene names
Name:Alox15
Synonyms:Alox12l
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length663 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Converts arachidonic acid into 12-hydroperoxyeicosatetraenoic acid/12-HPETE and 15-hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. Beside its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass. Ref.1 Ref.2 Ref.4 Ref.5

Catalytic activity

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. Ref.1 Ref.2

Arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate. Ref.1 Ref.2

Cofactor

Binds 1 iron ion per subunit.

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.

Subunit structure

Interacts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade By similarity.

Subcellular location

Cytoplasmcytosol. Cell membrane By similarity. Lipid droplet By similarity. Note: Translocates from the cytosol to the plasma membrane when stimulated by IL13/interleukin-13 and in macrophages binding apoptotic cells By similarity. Ref.2

Tissue specificity

Detected in leukocytes, lung and aorta. Ref.1

Sequence similarities

Belongs to the lipoxygenase family.

Contains 1 lipoxygenase domain.

Contains 1 PLAT domain.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentCell membrane
Cytoplasm
Lipid droplet
Membrane
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic cell clearance

Inferred from sequence or structural similarity. Source: UniProtKB

arachidonic acid metabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

bone mineralization

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to interleukin-13

Inferred from sequence or structural similarity. Source: UniProtKB

fatty acid oxidation

Inferred from sequence or structural similarity. Source: UniProtKB

hepoxilin biosynthetic process

Inferred from direct assay Ref.5. Source: UniProtKB

icosanoid biosynthetic process

Non-traceable author statement Ref.4. Source: UniProtKB

lipoxin A4 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxygenase pathway

Inferred from direct assay Ref.2. Source: RGD

negative regulation of adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell volume

Traceable author statement Ref.4. Source: UniProtKB

ossification

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatidylethanolamine biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell growth

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of cell-substrate adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of heterotypic cell-cell adhesion

Inferred from mutant phenotype PubMed 15576842. Source: RGD

regulation of engulfment of apoptotic cell

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of membrane potential

Traceable author statement Ref.4. Source: UniProtKB

regulation of peroxisome proliferator activated receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from sequence or structural similarity. Source: UniProtKB

wound healing

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytosol

Inferred from direct assay Ref.4. Source: UniProtKB

lipid particle

Inferred from sequence or structural similarity. Source: UniProtKB

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

sarcolemma

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionarachidonate 12-lipoxygenase activity

Inferred from direct assay Ref.2. Source: RGD

arachidonate 15-lipoxygenase activity

Inferred from direct assay Ref.1. Source: RGD

hepoxilin A3 synthase activity

Inferred from direct assay Ref.4. Source: RGD

hepoxilin-epoxide hydrolase activity

Inferred from direct assay Ref.4. Source: UniProtKB

iron ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

potassium channel inhibitor activity

Traceable author statement Ref.4. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 663662Arachidonate 15-lipoxygenase
PRO_0000220687

Regions

Domain2 – 115114PLAT
Domain116 – 663548Lipoxygenase

Sites

Metal binding3611Iron; catalytic By similarity
Metal binding3661Iron; catalytic By similarity
Metal binding5411Iron; catalytic By similarity
Metal binding5451Iron; catalytic By similarity
Metal binding6631Iron; via carboxylate; catalytic By similarity

Experimental info

Sequence conflict551E → G in AAB30132. Ref.2
Sequence conflict3711V → L in AAA41532. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q02759 [UniParc].

Last modified October 16, 2013. Version 3.
Checksum: C732D3EB22CA0411

FASTA66375,378
        10         20         30         40         50         60 
MGVYRIRVST GDSKYAGSNN EVYLWLVGQH GEASLGKLLR PCRDSEAEFK VDVSEYLGPL 

        70         80         90        100        110        120 
LFVRVQKWHY LTDDAWFCNW ISVKGPGDQG SEYMFPCYRW VQGRSILSLP EGTGCTVVED 

       130        140        150        160        170        180 
SQGLFRKHRE EELEERRSLY RWGNWKDGSI LNVAAASISD LPVDQRFRED KRIEFEASQV 

       190        200        210        220        230        240 
IGVMDTVVNF PINTVTCWKS LDDFNCVFKS GHTKMAERVR NSWKEDAFFG YQFLNGANPM 

       250        260        270        280        290        300 
VLKRSTCLPA RLVFPPGMEK LQAQLNKELQ KGTLFEADFF LLDGIKANVI LCSQQYLAAP 

       310        320        330        340        350        360 
LVMLKLMPDG QLLPIAIQLE LPKTGSTPPP IFTPSDPPMD WLLAKCWVRS SDLQLHELQA 

       370        380        390        400        410        420 
HLLRGHLMAE VFAVATMRCL PSVHPVFKLL VPHLLYTMEI NVRARSDLIS ERGFFDKAMS 

       430        440        450        460        470        480 
TGGGGHLDLL KQAGAFLTYC SLCPPDDLAE RGLLDIETCF YAKDALRLWQ IMNRYVVGMF 

       490        500        510        520        530        540 
NLHYKTDKAV QDDYELQSWC REITDIGLQG AQDRGFPTSL QSRAQACYFI TMCIFTCTAQ 

       550        560        570        580        590        600 
HSSVHLGQLD WFYWVPNAPC TMRLPPPTTK EATMEKLMAT LPNPNQSTLQ INVVWLLGRR 

       610        620        630        640        650        660 
QAVMVPLGQH SEEHFPNPEA KAVLKKFREE LAALDKEIEI RNKSLDIPYE YLRPSMVENS 


VAI 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of a 12-lipoxygenase cDNA from rat brain."
Watanabe T., Medina J.F., Haeggstroem J.Z., Raadmark O.P., Samuelsson B.
Eur. J. Biochem. 212:605-612(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Brain.
[2]"Arachidonate 12-lipoxygenase of rat pineal glands: catalytic properties and primary structure deduced from its cDNA."
Hada T., Hagiya H., Suzuki H., Arakawa T., Nakamura M., Matsuda S., Yoshimoto T., Yamamoto S., Azekawa T., Morita Y., Ishimura K., Kim H.Y.
Biochim. Biophys. Acta 1211:221-228(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
Tissue: Pineal gland.
[3]"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. expand/collapse author list , 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.
[4]"The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity."
Nigam S., Patabhiraman S., Ciccoli R., Ishdorj G., Schwarz K., Petrucev B., Kuehn H., Haeggstroem J.Z.
J. Biol. Chem. 279:29023-29030(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN HEPOXILIN A3 SYNTHESIS.
[5]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L06040 mRNA. Translation: AAA41532.1.
S69383 mRNA. Translation: AAB30132.1.
AABR06064408 Genomic DNA. No translation available.
PIRI52462.
S30051.
RefSeqNP_112272.2. NM_031010.2.
UniGeneRn.11318.

3D structure databases

ProteinModelPortalQ02759.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000026038.

Chemistry

BindingDBQ02759.
ChEMBLCHEMBL2741.

Proteomic databases

PaxDbQ02759.
PRIDEQ02759.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000026038; ENSRNOP00000026038; ENSRNOG00000019183.
GeneID81639.
KEGGrno:81639.
UCSCRGD:70493. rat.

Organism-specific databases

CTD246.
RGD70493. Alox15.

Phylogenomic databases

eggNOGNOG133298.
GeneTreeENSGT00550000074415.
HOGENOMHOG000234358.
HOVERGENHBG005150.
InParanoidQ02759.
KOK00460.
OrthoDBEOG7B05CG.
TreeFamTF105320.

Enzyme and pathway databases

UniPathwayUPA00881.

Gene expression databases

GenevestigatorQ02759.

Family and domain databases

Gene3D2.60.60.20. 1 hit.
InterProIPR008976. Lipase_LipOase.
IPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERPTHR11771. PTHR11771. 1 hit.
PfamPF00305. Lipoxygenase. 2 hits.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio35583133.

Entry information

Entry nameLOX15_RAT
AccessionPrimary (citable) accession number: Q02759
Secondary accession number(s): F1MA51
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 16, 2013
Last modified: April 16, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways