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P12530 (LOX15_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
Short name=L-12LO
EC=1.13.11.31
Arachidonate omega-6 lipoxygenase
Erythroid cell-specific 15-lipoxygenase
Gene names
Name:ALOX15
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

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.2

Catalytic activity

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

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

Cofactor

Binds 1 iron ion per subunit By similarity.

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. Ref.2

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 By similarity. 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.

Sequence similarities

Belongs to the lipoxygenase family.

Contains 1 lipoxygenase domain.

Contains 1 PLAT domain.

Caution

According to the authors the mRNA described in Ref.2 may be encoded by a gene different from ALOX15.

Ontologies

Keywords
   Biological processFatty acid metabolism
Lipid metabolism
   Cellular componentCell membrane
Cytoplasm
Lipid droplet
Membrane
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
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.2. 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

hepoxilin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

linoleic acid metabolic process

Inferred from direct assay Ref.2. Source: UniProtKB

lipoxin A4 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxygenase pathway

Inferred from direct assay Ref.2. Source: UniProtKB

negative regulation of adaptive immune response

Inferred from sequence or structural similarity. 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-substrate adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of engulfment of apoptotic cell

Inferred from sequence or structural similarity. 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 sequence or structural similarity. 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

   Molecular_functionarachidonate 12-lipoxygenase activity

Inferred from direct assay Ref.2. Source: UniProtKB

arachidonate 15-lipoxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

iron ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.3
Chain2 – 663662Arachidonate 15-lipoxygenase
PRO_0000220699

Regions

Domain2 – 115114PLAT
Domain116 – 663548Lipoxygenase

Sites

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

Experimental info

Mutagenesis3531F → L: Changes the stereoselectivity of the oxygenation reaction to produce (12S)-HPETE instead of (15S)-HPETE. Ref.2
Sequence conflict421T → S in CAB10746. Ref.2
Sequence conflict641R → K in CAB10746. Ref.2
Sequence conflict1901N → D in AAB86978. Ref.3
Sequence conflict1941I → V in AAB86978. Ref.3
Sequence conflict3531F → L in CAB10746. Ref.2

Secondary structure

.................................................................................................... 663
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P12530 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: C3391E1E6E7930BF

FASTA66375,310
        10         20         30         40         50         60 
MGVYRVCVST GASIYAGSKN KVELWLVGQH GEVELGSCLR PTRNKEEEFK VNVSKYLGSL 

        70         80         90        100        110        120 
LFVRLRKKHF LKEDAWFCNW ISVQALGAAE DKYWFPCYRW VVGDGVQSLP VGTGCTTVGD 

       130        140        150        160        170        180 
PQGLFQKHRE QELEERRKLY QWGSWKEGLI LNVAGSKLTD LPVDERFLED KKIDFEASLA 

       190        200        210        220        230        240 
WGLAELALKN SLNILAPWKT LDDFNRIFWC GRSKLARRVR DSWQEDSLFG YQFLNGANPM 

       250        260        270        280        290        300 
LLRRSVQLPA RLVFPPGMEE LQAQLEKELK AGTLFEADFA LLDNIKANVI LYCQQYLAAP 

       310        320        330        340        350        360 
LVMLKLQPDG KLMPMVIQLH LPKIGSSPPP LFLPTDPPMV WLLAKCWVRS SDFQVHELNS 

       370        380        390        400        410        420 
HLLRGHLMAE VFTVATMRCL PSIHPVFKLI VPHLRYTLEI NVRARNGLVS DFGIFDQIMS 

       430        440        450        460        470        480 
TGGGGHVQLL QQAGAFLTYR SFCPPDDLAD RGLLGVESSF YAQDALRLWE IISRYVQGIM 

       490        500        510        520        530        540 
GLYYKTDEAV RDDLELQSWC REITEIGLQG AQKQGFPTSL QSVAQACHFV TMCIFTCTGQ 

       550        560        570        580        590        600 
HSSIHLGQLD WFTWVPNAPC TMRLPPPTTK DATLETVMAT LPNLHQSSLQ MSIVWQLGRD 

       610        620        630        640        650        660 
QPIMVPLGQH QEEYFSGPEP RAVLEKFREE LAIMDKEIEV RNEKLDIPYE YLRPSIVENS 


VAI 

« Hide

References

[1]"The promoter structure and complete sequence of the gene encoding the rabbit erythroid cell-specific 15-lipoxygenase."
O'Prey J., Chester J., Thiele B.J., Janetzki S., Prehn S., Fleming J., Harrison P.R.
Gene 84:493-499(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Simultaneous expression of leukocyte-type 12-lipoxygenase and reticulocyte-type 15-lipoxygenase in rabbits."
Berger M., Schwarz K., Thiele H., Reimann I., Huth A., Borngraeber S., Kuehn H., Thiele B.-J.
J. Mol. Biol. 278:935-948(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, MUTAGENESIS OF PHE-353.
[3]"The complete sequence of the rabbit erythroid cell-specific 15-lipoxygenase mRNA: comparison of the predicted amino acid sequence of the erythrocyte lipoxygenase with other lipoxygenases."
Fleming J., Thiele B.J., Chester J., O'Prey J., Janetzki S., Aitken A., Anton I.A., Rapoport S.M., Harrison P.R.
Gene 79:181-188(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-31.
[4]"Cloning of a rabbit erythroid-cell-specific lipoxygenase mRNA."
Thiele B.J., Fleming J., Kasturi K., O'Prey J., Black E., Chester J., Rapoport S.M., Harrison P.R.
Gene 57:111-119(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-31.
[5]"Structure of the mRNA and of the gene coding for the rabbit erythroid 15-lipoxygenase."
Thiele B.J., Fleming J., Chester J., O'Prey J., Prehn S., Janetzki S., Rapoport S.M., Harrison P.R.
Biomed. Biochim. Acta 49:S17-S24(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], GENE STRUCTURE.
[6]"The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity."
Gillmor S.A., Villasenor A., Fletterick R., Sigal E., Browner M.F.
Nat. Struct. Biol. 4:1003-1009(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH IRON AND SUBSTRATE ANALOG.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M33291 Genomic DNA. Translation: AAA75014.1.
Z97654 mRNA. Translation: CAB10746.1.
M27214 mRNA. Translation: AAB86978.1.
M22617 mRNA. Translation: AAA31385.1.
PIRJQ0018.
RefSeqNP_001075751.1. NM_001082282.1.
NP_001139620.1. NM_001146148.1.
UniGeneOcu.2185.
Ocu.7470.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOXX-ray2.40A2-663[»]
2P0MX-ray2.40A/B2-663[»]
ProteinModelPortalP12530.
SMRP12530. Positions 2-663.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9986.ENSOCUP00000017072.

Chemistry

BindingDBP12530.
ChEMBLCHEMBL4358.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009114.
100271999.

Organism-specific databases

CTD239.
246.

Phylogenomic databases

eggNOGNOG133298.
HOGENOMHOG000234358.
HOVERGENHBG005150.

Enzyme and pathway databases

UniPathwayUPA00881.

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

EvolutionaryTraceP12530.

Entry information

Entry nameLOX15_RABIT
AccessionPrimary (citable) accession number: P12530
Secondary accession number(s): O19043
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 120 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways