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Protein

Arachidonate 15-lipoxygenase

Gene

ALOX15

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. In addition to 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.2 Publications

Catalytic activityi

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.1 Publication
Arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate.2 Publications

Cofactori

Fe cationNote: Binds 1 Fe cation per subunit.

Pathwayi: hydroperoxy eicosatetraenoic acid biosynthesis

This protein is involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis, which is part of Lipid metabolism.1 Publication
View all proteins of this organism that are known to be involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi361 – 3611Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi366 – 3661Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi541 – 5411Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi545 – 5451Iron; catalyticPROSITE-ProRule annotation1 Publication
Metal bindingi663 – 6631Iron; via carboxylate; catalyticPROSITE-ProRule annotation1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

Calcium, Iron, Lipid-binding, Metal-binding

Enzyme and pathway databases

BRENDAi1.13.11.33. 1749.
UniPathwayiUPA00881.

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 15-lipoxygenase (EC:1.13.11.332 Publications)
Short name:
15-LOX
Alternative name(s):
12/15-lipoxygenase
Arachidonate 12-lipoxygenase, leukocyte-type (EC:1.13.11.311 Publication)
Short name:
12-LOX
Short name:
L-12LO
Arachidonate omega-6 lipoxygenase
Erythroid cell-specific 15-lipoxygenase
Gene namesi
Name:ALOX15
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Cell membrane 1 Publication; Peripheral membrane protein 1 Publication
  • 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). Predominantly cytosolic; becomes enriched at membranes upon calcium binding.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Lipid droplet, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi353 – 3531F → L: Changes the stereoselectivity of the oxygenation reaction to produce (12S)-HPETE instead of (15S)-HPETE. 1 Publication

Chemistry

ChEMBLiCHEMBL4358.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemoved1 Publication
Chaini2 – 663662Arachidonate 15-lipoxygenasePRO_0000220699Add
BLAST

Expressioni

Tissue specificityi

Detected in reticulocytes (at protein level).1 Publication

Interactioni

Subunit structurei

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

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000017072.

Chemistry

BindingDBiP12530.

Structurei

Secondary structure

1
663
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 108Combined sources
Beta strandi12 – 154Combined sources
Beta strandi19 – 3012Combined sources
Beta strandi32 – 398Combined sources
Beta strandi46 – 527Combined sources
Beta strandi59 – 6810Combined sources
Beta strandi70 – 723Combined sources
Beta strandi76 – 8813Combined sources
Beta strandi93 – 1019Combined sources
Beta strandi103 – 1053Combined sources
Beta strandi107 – 1104Combined sources
Helixi126 – 13914Combined sources
Beta strandi152 – 1543Combined sources
Helixi158 – 1603Combined sources
Helixi163 – 1653Combined sources
Helixi169 – 1757Combined sources
Helixi189 – 1924Combined sources
Helixi193 – 1953Combined sources
Helixi201 – 2066Combined sources
Helixi214 – 2229Combined sources
Helixi226 – 23510Combined sources
Helixi259 – 27012Combined sources
Beta strandi274 – 2785Combined sources
Helixi280 – 2823Combined sources
Beta strandi301 – 3066Combined sources
Turni308 – 3103Combined sources
Beta strandi312 – 3187Combined sources
Helixi338 – 35821Combined sources
Helixi359 – 3657Combined sources
Helixi366 – 37914Combined sources
Helixi385 – 3906Combined sources
Helixi391 – 3944Combined sources
Helixi397 – 4048Combined sources
Turni405 – 4084Combined sources
Helixi414 – 4185Combined sources
Turni420 – 4245Combined sources
Helixi425 – 43410Combined sources
Helixi439 – 4424Combined sources
Helixi444 – 4507Combined sources
Helixi460 – 48021Combined sources
Turni481 – 4833Combined sources
Helixi487 – 4915Combined sources
Helixi494 – 50411Combined sources
Turni505 – 5095Combined sources
Helixi511 – 5144Combined sources
Helixi523 – 53614Combined sources
Helixi539 – 5457Combined sources
Helixi548 – 5514Combined sources
Beta strandi552 – 5543Combined sources
Helixi555 – 5573Combined sources
Beta strandi568 – 5703Combined sources
Helixi574 – 5807Combined sources
Helixi584 – 59613Combined sources
Helixi618 – 64326Combined sources
Beta strandi645 – 6473Combined sources
Turni654 – 6563Combined sources
Beta strandi657 – 6604Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOXX-ray2.40A2-663[»]
2P0MX-ray2.40A/B2-663[»]
ProteinModelPortaliP12530.
SMRiP12530. Positions 2-663.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12530.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 115114PLATPROSITE-ProRule annotationAdd
BLAST
Domaini116 – 663548LipoxygenasePROSITE-ProRule annotationAdd
BLAST

Domaini

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

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated
Contains 1 lipoxygenase domain.PROSITE-ProRule annotation
Contains 1 PLAT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IKAN. Eukaryota.
ENOG410YN4N. LUCA.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiP12530.
KOiK00460.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. 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.

Sequence processingi: The displayed sequence is further processed into a mature form.

P12530-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGVYRVCVST GASIYAGSKN KVELWLVGQH GEVELGSCLR PTRNKEEEFK
60 70 80 90 100
VNVSKYLGSL LFVRLRKKHF LKEDAWFCNW ISVQALGAAE DKYWFPCYRW
110 120 130 140 150
VVGDGVQSLP VGTGCTTVGD PQGLFQKHRE QELEERRKLY QWGSWKEGLI
160 170 180 190 200
LNVAGSKLTD LPVDERFLED KKIDFEASLA WGLAELALKN SLNILAPWKT
210 220 230 240 250
LDDFNRIFWC GRSKLARRVR DSWQEDSLFG YQFLNGANPM LLRRSVQLPA
260 270 280 290 300
RLVFPPGMEE LQAQLEKELK AGTLFEADFA LLDNIKANVI LYCQQYLAAP
310 320 330 340 350
LVMLKLQPDG KLMPMVIQLH LPKIGSSPPP LFLPTDPPMV WLLAKCWVRS
360 370 380 390 400
SDFQVHELNS HLLRGHLMAE VFTVATMRCL PSIHPVFKLI VPHLRYTLEI
410 420 430 440 450
NVRARNGLVS DFGIFDQIMS TGGGGHVQLL QQAGAFLTYR SFCPPDDLAD
460 470 480 490 500
RGLLGVESSF YAQDALRLWE IISRYVQGIM GLYYKTDEAV RDDLELQSWC
510 520 530 540 550
REITEIGLQG AQKQGFPTSL QSVAQACHFV TMCIFTCTGQ HSSIHLGQLD
560 570 580 590 600
WFTWVPNAPC TMRLPPPTTK DATLETVMAT LPNLHQSSLQ MSIVWQLGRD
610 620 630 640 650
QPIMVPLGQH QEEYFSGPEP RAVLEKFREE LAIMDKEIEV RNEKLDIPYE
660
YLRPSIVENS VAI
Length:663
Mass (Da):75,310
Last modified:January 23, 2007 - v3
Checksum:iC3391E1E6E7930BF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421T → S in CAB10746 (PubMed:9600854).Curated
Sequence conflicti64 – 641R → K in CAB10746 (PubMed:9600854).Curated
Sequence conflicti190 – 1901N → D in AAB86978 (PubMed:2777088).Curated
Sequence conflicti194 – 1941I → V in AAB86978 (PubMed:2777088).Curated
Sequence conflicti353 – 3531F → L in CAB10746 (PubMed:9600854).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33291 Genomic DNA. Translation: AAA75014.1.
Z97654 mRNA. Translation: CAB10746.1.
M27214 mRNA. Translation: AAB86978.1.
M22617 mRNA. Translation: AAA31385.1.
PIRiJQ0018.
RefSeqiNP_001075751.1. NM_001082282.1.
NP_001139620.1. NM_001146148.1.
UniGeneiOcu.2185.
Ocu.7470.

Genome annotation databases

GeneIDi100009114.
100271999.
KEGGiocu:100009114.
ocu:100271999.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M33291 Genomic DNA. Translation: AAA75014.1.
Z97654 mRNA. Translation: CAB10746.1.
M27214 mRNA. Translation: AAB86978.1.
M22617 mRNA. Translation: AAA31385.1.
PIRiJQ0018.
RefSeqiNP_001075751.1. NM_001082282.1.
NP_001139620.1. NM_001146148.1.
UniGeneiOcu.2185.
Ocu.7470.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1LOXX-ray2.40A2-663[»]
2P0MX-ray2.40A/B2-663[»]
ProteinModelPortaliP12530.
SMRiP12530. Positions 2-663.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000017072.

Chemistry

BindingDBiP12530.
ChEMBLiCHEMBL4358.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100009114.
100271999.
KEGGiocu:100009114.
ocu:100271999.

Organism-specific databases

CTDi239.
246.

Phylogenomic databases

eggNOGiENOG410IKAN. Eukaryota.
ENOG410YN4N. LUCA.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiP12530.
KOiK00460.

Enzyme and pathway databases

UniPathwayiUPA00881.
BRENDAi1.13.11.33. 1749.

Miscellaneous databases

EvolutionaryTraceiP12530.
PROiP12530.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. 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

  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. "Membrane translocation of 15-lipoxygenase in hematopoietic cells is calcium-dependent and activates the oxygenase activity of the enzyme."
    Brinckmann R., Schnurr K., Heydeck D., Rosenbach T., Kolde G., Kuehn H.
    Blood 91:64-74(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "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.

Entry informationi

Entry nameiLOX15_RABIT
AccessioniPrimary (citable) accession number: P12530
Secondary accession number(s): O19043
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 23, 2007
Last modified: June 8, 2016
This is version 136 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

According to the authors the mRNA described in PubMed:9600854 may be encoded by a gene different from ALOX15.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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 one 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.