Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)DescriptionActionsGraphical viewLength
Metal bindingi361Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi366Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi541Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi545Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi663Iron; via carboxylate; catalyticPROSITE-ProRule annotation1 Publication1

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.

Chemistry databases

SwissLipidsiSLP:000001603.

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)DescriptionActionsGraphical viewLength
Mutagenesisi353F → L: Changes the stereoselectivity of the oxygenation reaction to produce (12S)-HPETE instead of (15S)-HPETE. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL4358.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002206992 – 663Arachidonate 15-lipoxygenaseAdd BLAST662

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 databases

BindingDBiP12530.

Structurei

Secondary structure

1663
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 10Combined sources8
Beta strandi12 – 15Combined sources4
Beta strandi19 – 30Combined sources12
Beta strandi32 – 39Combined sources8
Beta strandi46 – 52Combined sources7
Beta strandi59 – 68Combined sources10
Beta strandi70 – 72Combined sources3
Beta strandi76 – 88Combined sources13
Beta strandi93 – 101Combined sources9
Beta strandi103 – 105Combined sources3
Beta strandi107 – 110Combined sources4
Helixi126 – 139Combined sources14
Beta strandi152 – 154Combined sources3
Helixi158 – 160Combined sources3
Helixi163 – 165Combined sources3
Helixi169 – 175Combined sources7
Helixi189 – 192Combined sources4
Helixi193 – 195Combined sources3
Helixi201 – 206Combined sources6
Helixi214 – 222Combined sources9
Helixi226 – 235Combined sources10
Helixi259 – 270Combined sources12
Beta strandi274 – 278Combined sources5
Helixi280 – 282Combined sources3
Beta strandi301 – 306Combined sources6
Turni308 – 310Combined sources3
Beta strandi312 – 318Combined sources7
Helixi338 – 358Combined sources21
Helixi359 – 365Combined sources7
Helixi366 – 379Combined sources14
Helixi385 – 390Combined sources6
Helixi391 – 394Combined sources4
Helixi397 – 404Combined sources8
Turni405 – 408Combined sources4
Helixi414 – 418Combined sources5
Turni420 – 424Combined sources5
Helixi425 – 434Combined sources10
Helixi439 – 442Combined sources4
Helixi444 – 450Combined sources7
Helixi460 – 480Combined sources21
Turni481 – 483Combined sources3
Helixi487 – 491Combined sources5
Helixi494 – 504Combined sources11
Turni505 – 509Combined sources5
Helixi511 – 514Combined sources4
Helixi523 – 536Combined sources14
Helixi539 – 545Combined sources7
Helixi548 – 551Combined sources4
Beta strandi552 – 554Combined sources3
Helixi555 – 557Combined sources3
Beta strandi568 – 570Combined sources3
Helixi574 – 580Combined sources7
Helixi584 – 596Combined sources13
Helixi618 – 643Combined sources26
Beta strandi645 – 647Combined sources3
Turni654 – 656Combined sources3
Beta strandi657 – 660Combined sources4

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP12530.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 115PLATPROSITE-ProRule annotationAdd BLAST114
Domaini116 – 663LipoxygenasePROSITE-ProRule annotationAdd BLAST548

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)DescriptionActionsGraphical viewLength
Sequence conflicti42T → S in CAB10746 (PubMed:9600854).Curated1
Sequence conflicti64R → K in CAB10746 (PubMed:9600854).Curated1
Sequence conflicti190N → D in AAB86978 (PubMed:2777088).Curated1
Sequence conflicti194I → V in AAB86978 (PubMed:2777088).Curated1
Sequence conflicti353F → L in CAB10746 (PubMed:9600854).Curated1

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LOXX-ray2.40A2-663[»]
2P0MX-ray2.40A/B2-663[»]
ProteinModelPortaliP12530.
SMRiP12530.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000017072.

Chemistry databases

BindingDBiP12530.
ChEMBLiCHEMBL4358.
SwissLipidsiSLP:000001603.

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...

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: November 2, 2016
This is version 138 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.