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Protein

Arachidonate 15-lipoxygenase

Gene

ALOX15

Organism
Sus scrofa (Pig)
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.1 Publication

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.1 Publication

Cofactori

Fe cationPROSITE-ProRule annotation1 PublicationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation1 Publication

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; catalytic1
Metal bindingi366Iron; catalytic1
Metal bindingi541Iron; catalytic1
Metal bindingi545Iron; catalytic1
Metal bindingi663Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • arachidonate 12-lipoxygenase activity Source: UniProtKB
  • arachidonate 15-lipoxygenase activity Source: UniProtKB
  • iron ion binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB

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

BRENDAi1.13.11.31. 6170.
ReactomeiR-SSC-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
R-SSC-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.
R-SSC-2142770. Synthesis of 15-eicosatetraenoic acid derivatives.
UniPathwayiUPA00881.

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 15-lipoxygenase (EC:1.13.11.331 Publication)
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
Arachidonate omega-6 lipoxygenase
Erythroid cell-specific 15-lipoxygenase
Gene namesi
Name:ALOX15
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Chromosome 12

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Cell membrane By similarity; 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).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
Mutagenesisi106I → V: No effect on the stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi128H → L: No specific effect on enzymatic activity and iron-binding. 1 Publication1
Mutagenesisi356H → L: No specific effect on enzymatic activity and iron-binding. 1 Publication1
Mutagenesisi361H → L or Q: Loss of enzymatic activity and iron-binding. 1 Publication1
Mutagenesisi366H → L: Loss of enzymatic activity and iron-binding. 1 Publication1
Mutagenesisi384H → L: Labile enzyme with normal enzymatic activity. 1 Publication1
Mutagenesisi393H → L: Labile enzyme with loss of enzymatic activity. 1 Publication1
Mutagenesisi398M → L: No effect on the stereoselectivity of the oxygenation reaction. 1 Publication1
Mutagenesisi418V → 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. 1 Publication1
Mutagenesisi419V → 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. 1 Publication1
Mutagenesisi426H → L: Decreased enzymatic activity without effect on iron-binding. 1 Publication1
Mutagenesisi533C → S: No specific effect on enzymatic activity and iron-binding. 1 Publication1
Mutagenesisi541H → L: Loss of enzymatic activity and iron-binding. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2381.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00002206842 – 663Arachidonate 15-lipoxygenaseAdd BLAST662

Proteomic databases

PaxDbiP16469.
PeptideAtlasiP16469.
PRIDEiP16469.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSSSCG00000017923.
GenevisibleiP16469. SS.

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

STRINGi9823.ENSSSCP00000018988.

Chemistry databases

BindingDBiP16469.

Structurei

Secondary structure

1663
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi126 – 139Combined sources14
Helixi158 – 160Combined sources3
Helixi163 – 165Combined sources3
Helixi169 – 193Combined sources25
Helixi201 – 207Combined sources7
Helixi214 – 222Combined sources9
Helixi226 – 235Combined sources10
Helixi259 – 270Combined sources12
Beta strandi274 – 278Combined sources5
Helixi280 – 282Combined sources3
Beta strandi301 – 306Combined sources6
Beta strandi312 – 318Combined sources7
Helixi338 – 358Combined sources21
Helixi359 – 365Combined sources7
Helixi366 – 379Combined sources14
Helixi385 – 390Combined sources6
Helixi391 – 394Combined sources4
Helixi397 – 407Combined sources11
Helixi414 – 418Combined sources5
Turni420 – 424Combined sources5
Helixi425 – 436Combined sources12
Helixi440 – 442Combined sources3
Helixi444 – 450Combined sources7
Helixi460 – 483Combined sources24
Helixi487 – 491Combined sources5
Helixi494 – 505Combined sources12
Turni506 – 509Combined sources4
Helixi512 – 514Combined sources3
Helixi523 – 537Combined sources15
Helixi539 – 545Combined sources7
Helixi548 – 551Combined sources4
Beta strandi552 – 554Combined sources3
Helixi555 – 557Combined sources3
Beta strandi568 – 570Combined sources3
Helixi574 – 580Combined sources7
Helixi584 – 598Combined sources15
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
3RDEX-ray1.89A/B/C/D112-663[»]
SMRiP16469.
ModBaseiSearch...
MobiDBiSearch...

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.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiP16469.
KOiK00460.
OMAiLTCWKDL.
OrthoDBiEOG091G04A4.
TreeFamiTF105320.

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.

P16469-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGLYRVRVST GSSFYAGSQN QVQLWLVGQH GEAALGWCLR PARGKETEFS
60 70 80 90 100
VDVSEYLGPL LFVKLRKRHL LQDDAWFCNW ISVQGPGANG DEFRFPCYRW
110 120 130 140 150
VEGDRILSLP EGTARTVVDD PQGLFKKHRE EELAERRKLY RWGNWKDGLI
160 170 180 190 200
LNIASTGIHD LPVDERFLED KRIDFEASLA KGLADLAVKD SLNVLMSWNS
210 220 230 240 250
LDSFNRIFWC GQSKLAERVR DSWKEDALFG YQFLNGTNPM LLRHSVELPA
260 270 280 290 300
RLKFPPGMEE LQAQLEKELQ GGTLFEADFS LLDGIKANVI LCSQQYLAVP
310 320 330 340 350
LVMLKLQPDG KLLPMVIQLQ LPHEGSPLPP LFLPTDPPMV WLLAKCWVRS
360 370 380 390 400
SDFQLHELHS HLLRGHLMAE VIAVATMRCL PSIHPIFKLL IPHFRYTMEI
410 420 430 440 450
NVRARNGLVS DLGIFDQVVS TGGGGHVELL RRAAALLTYS SFCPPDDLAD
460 470 480 490 500
RGLLGVESSF YAQDALRLWE VISRYVEGIV SLHYKTDESV KEDLELQAWC
510 520 530 540 550
REFTEIGLLG AQDRGFPVSL QSKEQLCHFV TMCIFTCTGQ HSSNHLGQLD
560 570 580 590 600
WYSWVPNAPC TMRLPPPTTK DATLETVMAT LPNFHQASLQ MSITWQLGRC
610 620 630 640 650
QPTMVALGQH EEEYFSGPGP KAVLTKFREE LAALDKDIEV RNAKLALPYE
660
YLRPSRVENS VAI
Length:663
Mass (Da):75,004
Last modified:October 16, 2013 - v3
Checksum:i5E3864A7A3FDEF71
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti218R → Q in AAA31068 (PubMed:2315307).Curated1
Sequence conflicti218R → Q in BAA01471 (PubMed:2315307).Curated1
Sequence conflicti323H → R in AAA31068 (PubMed:2315307).Curated1
Sequence conflicti323H → R in BAA01471 (PubMed:2315307).Curated1
Sequence conflicti494L → F in AAA31068 (PubMed:2315307).Curated1
Sequence conflicti494L → F in BAA01471 (PubMed:2315307).Curated1
Sequence conflicti553S → T in AAA31068 (PubMed:2315307).Curated1
Sequence conflicti553S → T in BAA01471 (PubMed:2315307).Curated1
Sequence conflicti623V → G in BAA01471 (PubMed:2315307).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31417 mRNA. Translation: AAA31068.1.
D10621 Genomic DNA. Translation: BAA01471.1.
CU972403 Genomic DNA. No translation available.
PIRiA35087.
RefSeqiNP_999096.1. NM_213931.1.
UniGeneiSsc.10974.

Genome annotation databases

EnsembliENSSSCT00000019506; ENSSSCP00000018988; ENSSSCG00000017923.
GeneIDi396971.
KEGGissc:396971.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31417 mRNA. Translation: AAA31068.1.
D10621 Genomic DNA. Translation: BAA01471.1.
CU972403 Genomic DNA. No translation available.
PIRiA35087.
RefSeqiNP_999096.1. NM_213931.1.
UniGeneiSsc.10974.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RDEX-ray1.89A/B/C/D112-663[»]
SMRiP16469.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000018988.

Chemistry databases

BindingDBiP16469.
ChEMBLiCHEMBL2381.

Proteomic databases

PaxDbiP16469.
PeptideAtlasiP16469.
PRIDEiP16469.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000019506; ENSSSCP00000018988; ENSSSCG00000017923.
GeneIDi396971.
KEGGissc:396971.

Organism-specific databases

CTDi246.

Phylogenomic databases

eggNOGiENOG410IKAN. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiP16469.
KOiK00460.
OMAiLTCWKDL.
OrthoDBiEOG091G04A4.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00881.
BRENDAi1.13.11.31. 6170.
ReactomeiR-SSC-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
R-SSC-2142712. Synthesis of 12-eicosatetraenoic acid derivatives.
R-SSC-2142770. Synthesis of 15-eicosatetraenoic acid derivatives.

Gene expression databases

BgeeiENSSSCG00000017923.
GenevisibleiP16469. SS.

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_PIG
AccessioniPrimary (citable) accession number: P16469
Secondary accession number(s): F1RFT4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 16, 2013
Last modified: November 30, 2016
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

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.