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Protein

Arachidonate 15-lipoxygenase

Gene

ALOX15

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandCalcium, 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
SABIO-RKiP16469
UniPathwayiUPA00881

Chemistry databases

SwissLipidsiSLP:000001604

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: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ChainiPRO_00002206841 – 663Arachidonate 15-lipoxygenaseAdd BLAST663

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
ExpressionAtlasiP16469 differential
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

Phylogenomic databases

eggNOGiENOG410IKAN Eukaryota
ENOG410YN4N LUCA
HOGENOMiHOG000234358
HOVERGENiHBG005150
InParanoidiP16469
KOiK00460
OMAiLTCWKDL
OrthoDBiEOG091G04A4
TreeFamiTF105320

Family and domain databases

InterProiView protein in InterPro
IPR000907 LipOase
IPR013819 LipOase_C
IPR036226 LipOase_C_sf
IPR020834 LipOase_CS
IPR020833 LipOase_Fe_BS
IPR001885 LipOase_mml
IPR001024 PLAT/LH2_dom
IPR036392 PLAT/LH2_dom_sf
PANTHERiPTHR11771 PTHR11771, 1 hit
PfamiView protein in Pfam
PF00305 Lipoxygenase, 1 hit
PF01477 PLAT, 1 hit
PRINTSiPR00087 LIPOXYGENASE
PR00467 MAMLPOXGNASE
SMARTiView protein in SMART
SM00308 LH2, 1 hit
SUPFAMiSSF48484 SSF48484, 1 hit
SSF49723 SSF49723, 1 hit
PROSITEiView protein in PROSITE
PS00711 LIPOXYGENASE_1, 1 hit
PS00081 LIPOXYGENASE_2, 1 hit
PS51393 LIPOXYGENASE_3, 1 hit
PS50095 PLAT, 1 hit

Sequencei

Sequence statusi: Complete.

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

GeneIDi396971
KEGGissc:396971

Similar proteinsi

Entry informationi

Entry nameiLOX15_PIG
AccessioniPrimary (citable) accession number: P16469
Secondary accession number(s): F1RFT4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: October 16, 2013
Last modified: March 28, 2018
This is version 143 of the entry and version 3 of the sequence. See 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
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Main funding by: National Institutes of Health