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P16469 (LOX15_PIG) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. 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
EC=1.13.11.31
Arachidonate omega-6 lipoxygenase
Erythroid cell-specific 15-lipoxygenase
Gene names
Name:ALOX15
OrganismSus scrofa (Pig) [Reference proteome]
Taxonomic identifier9823 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus

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.4

Catalytic activity

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate. Ref.4

Arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate. Ref.4

Cofactor

Binds 1 iron ion per subunit. Ref.4

Pathway

Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. Ref.4

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; Peripheral membrane protein By similarity. Lipid droplet By similarity. Note: Predominantly cytosolic; becomes enriched at membranes upon calcium binding. Translocates from the cytosol to the plasma membrane when stimulated by IL13/interleukin-13 and in macrophages binding apoptotic cells By similarity.

Tissue specificity

Leukocytes, pituitary gland, lung and in very small amount in jejunum and spleen.

Domain

The PLAT domain can bind calcium ions; this promotes association with membranes By similarity.

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
   LigandCalcium
Iron
Lipid-binding
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.4. Source: UniProtKB

bone mineralization

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to calcium ion

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to interleukin-13

Inferred from sequence or structural similarity. Source: UniProtKB

linoleic acid metabolic process

Inferred from direct assay Ref.4. Source: UniProtKB

lipoxin A4 biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

lipoxygenase pathway

Inferred from direct assay Ref.4. 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

extrinsic component of cytoplasmic side of plasma membrane

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.4. Source: UniProtKB

arachidonate 15-lipoxygenase activity

Inferred from sequence or structural similarity. Source: UniProtKB

iron ion binding

Inferred from direct assay Ref.4. Source: UniProtKB

phosphatidylinositol-4,5-bisphosphate 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 By similarity
Chain2 – 663662Arachidonate 15-lipoxygenase
PRO_0000220684

Regions

Domain2 – 115114PLAT
Domain116 – 663548Lipoxygenase

Sites

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

Experimental info

Mutagenesis1061I → V: No effect on the stereoselectivity of the oxygenation reaction. Ref.4
Mutagenesis1281H → L: No specific effect on enzymatic activity and iron-binding. Ref.4
Mutagenesis3561H → L: No specific effect on enzymatic activity and iron-binding. Ref.4
Mutagenesis3611H → L or Q: Loss of enzymatic activity and iron-binding. Ref.4
Mutagenesis3661H → L: Loss of enzymatic activity and iron-binding. Ref.4
Mutagenesis3841H → L: Labile enzyme with normal enzymatic activity. Ref.4
Mutagenesis3931H → L: Labile enzyme with loss of enzymatic activity. Ref.4
Mutagenesis3981M → L: No effect on the stereoselectivity of the oxygenation reaction. Ref.4
Mutagenesis4181V → I: Alters the stereoselectivity of the oxygenation reaction. Changes the stereoselectivity of the oxygenation toward the production of (15S)-HPETE; when associated with M-419. Ref.4
Mutagenesis4191V → M: Alters the stereoselectivity of the oxygenation reaction. Changes the stereoselectivity of the oxygenation toward the production of (15S)-HPETE; when associated with I-418. Ref.4
Mutagenesis4261H → L: Decreased enzymatic activity without effect on iron-binding. Ref.4
Mutagenesis5331C → S: No specific effect on enzymatic activity and iron-binding. Ref.4
Mutagenesis5411H → L: Loss of enzymatic activity and iron-binding. Ref.4
Sequence conflict2181R → Q in AAA31068. Ref.1
Sequence conflict2181R → Q in BAA01471. Ref.1
Sequence conflict3231H → R in AAA31068. Ref.1
Sequence conflict3231H → R in BAA01471. Ref.1
Sequence conflict4941L → F in AAA31068. Ref.1
Sequence conflict4941L → F in BAA01471. Ref.1
Sequence conflict5531S → T in AAA31068. Ref.1
Sequence conflict5531S → T in BAA01471. Ref.1
Sequence conflict6231V → G in BAA01471. Ref.1

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
P16469 [UniParc].

Last modified October 16, 2013. Version 3.
Checksum: 5E3864A7A3FDEF71

FASTA66375,004
        10         20         30         40         50         60 
MGLYRVRVST GSSFYAGSQN QVQLWLVGQH GEAALGWCLR PARGKETEFS VDVSEYLGPL 

        70         80         90        100        110        120 
LFVKLRKRHL LQDDAWFCNW ISVQGPGANG DEFRFPCYRW VEGDRILSLP EGTARTVVDD 

       130        140        150        160        170        180 
PQGLFKKHRE EELAERRKLY RWGNWKDGLI LNIASTGIHD LPVDERFLED KRIDFEASLA 

       190        200        210        220        230        240 
KGLADLAVKD SLNVLMSWNS LDSFNRIFWC GQSKLAERVR DSWKEDALFG YQFLNGTNPM 

       250        260        270        280        290        300 
LLRHSVELPA RLKFPPGMEE LQAQLEKELQ GGTLFEADFS LLDGIKANVI LCSQQYLAVP 

       310        320        330        340        350        360 
LVMLKLQPDG KLLPMVIQLQ LPHEGSPLPP LFLPTDPPMV WLLAKCWVRS SDFQLHELHS 

       370        380        390        400        410        420 
HLLRGHLMAE VIAVATMRCL PSIHPIFKLL IPHFRYTMEI NVRARNGLVS DLGIFDQVVS 

       430        440        450        460        470        480 
TGGGGHVELL RRAAALLTYS SFCPPDDLAD RGLLGVESSF YAQDALRLWE VISRYVEGIV 

       490        500        510        520        530        540 
SLHYKTDESV KEDLELQAWC REFTEIGLLG AQDRGFPVSL QSKEQLCHFV TMCIFTCTGQ 

       550        560        570        580        590        600 
HSSNHLGQLD WYSWVPNAPC TMRLPPPTTK DATLETVMAT LPNFHQASLQ MSITWQLGRC 

       610        620        630        640        650        660 
QPTMVALGQH EEEYFSGPGP KAVLTKFREE LAALDKDIEV RNAKLALPYE YLRPSRVENS 


VAI 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and sequence analysis of the cDNA for arachidonate 12-lipoxygenase of porcine leukocytes."
Yoshimoto T., Suzuki H., Yamamoto S., Takai T., Yokoyama C., Tanabe T.
Proc. Natl. Acad. Sci. U.S.A. 87:2142-2146(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Leukocyte.
[2]"Molecular structure and function of the porcine arachidonate 12-lipoxygenase gene."
Arakawa T., Oshima T., Kishimoto K., Yoshimoto T., Yamamoto S.
J. Biol. Chem. 267:12188-12191(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]Porcine genome sequencing project
Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Site-directed mutagenesis studies on the iron-binding domain and the determinant for the substrate oxygenation site of porcine leukocyte arachidonate 12-lipoxygenase."
Suzuki H., Kishimoto K., Yoshimoto T., Yamamoto S., Kanai F., Ebina Y., Miyatake A., Tanabe T.
Biochim. Biophys. Acta 1210:308-316(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, IRON-BINDING, MUTAGENESIS OF ILE-106; HIS-128; HIS-356; HIS-361; HIS-366; HIS-384; HIS-393; MET-398; VAL-418; VAL-419; HIS-426; CYS-533 AND HIS-541.
[5]"Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex identifies a substrate-binding channel for catalysis."
Xu S., Mueser T.C., Marnett L.J., Funk M.O. Jr.
Structure 20:1490-1497(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 112-663 IN COMPLEX WITH INHIBITOR, IRON-BINDING.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M31417 mRNA. Translation: AAA31068.1.
D10621 Genomic DNA. Translation: BAA01471.1.
CU972403 Genomic DNA. No translation available.
PIRA35087.
RefSeqNP_999096.1. NM_213931.1.
UniGeneSsc.10974.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3RDEX-ray1.89A/B/C/D112-663[»]
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9823.ENSSSCP00000018988.

Chemistry

BindingDBP16469.
ChEMBLCHEMBL2381.

Proteomic databases

PaxDbP16469.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSSSCT00000019506; ENSSSCP00000018988; ENSSSCG00000017923.
GeneID396971.
KEGGssc:396971.

Organism-specific databases

CTD239.

Phylogenomic databases

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

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...

Entry information

Entry nameLOX15_PIG
AccessionPrimary (citable) accession number: P16469
Secondary accession number(s): F1RFT4
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 16, 2013
Last modified: July 9, 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways