UniProtKB - O35936 (ALOX8_MOUSE)
Protein
Polyunsaturated fatty acid lipoxygenase ALOX8
Gene
Alox8
Organism
Mus musculus (Mouse)
Status
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 (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). Catalyzes the peroxidation of arachidonate and linoleate into (8S)-HPETE and (9S)-HPODE respectively (PubMed:9305900, PubMed:10965849, PubMed:10625675, PubMed:16143298, PubMed:16112079, PubMed:15558016, PubMed:27435673). In addition to generate (8S)-HPETE from free arachidonic acid (AA), may produce other HETE isomers from phospholipid-esterified polyunsaturated fatty acids and minor products derived from (8S)-HPETE itself that may include leukotriene A4 and 8,15-diHPETE (PubMed:16143298, PubMed:16112079, PubMed:27435673). With free arachidonate as substrate, has no detectable 15S-lipoxygenase activity and only displays a 8S-lipoxygenase activity (PubMed:10625675, PubMed:16112079, PubMed:16143298, PubMed:15558016, PubMed:10965849, PubMed:9305900). However may have a 15S-lipoxygenase activity with (8S)-HPETE to produce (8S,15S)-diHPETE and when oxidizes directly arachidonic acid esterified to membrane-bound phospholipids to produce a phospholipid-esterified 15-HpETE (PubMed:27435673, PubMed:16112079, PubMed:16143298). May also catalyze (15S)-HPETE peroxidation to produce 8,15-diHPETE (PubMed:16112079). May play a role in keratinocyte differentiation through activation of the peroxisome proliferator activated receptor signaling pathway (PubMed:10965849).7 Publications
Catalytic activityi
- (9Z,12Z)-octadecadienoate + O2 = (9S)-hydroperoxy-(10E,12Z)-octadecadienoate1 Publication2 PublicationsEC:1.13.11.581 Publication2 PublicationsThis reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate1 Publication6 PublicationsThis reaction proceeds in the forward1 Publication direction.
- (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 = (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 = (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate2 PublicationsThis reaction proceeds in the forward1 Publication direction.
- 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + O2 = 1-octadecanoyl-2-(15-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphocholine1 PublicationThis reaction proceeds in the forward1 Publication direction.
- a 1-acyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol)1 PublicationThis reaction proceeds in the forward1 Publication direction.
- a 1-acyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-8Z,11Z,13E-eicosatrienoyl)-sn-glycero-3-phospho-(1D-myo-inositol)1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 9-hydroperoxy-(5Z,7E,11Z,14Z)-eicosatetraenoate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11-hydroperoxy-(5Z,8Z,12E,14Z)-eicosatetraenoate1 PublicationThis reaction proceeds in the forward1 Publication direction.
- This reaction proceeds in the forward1 Publication direction.
Cofactori
Fe cationPROSITE-ProRule annotationBy similarityNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotationBy similarity
Kineticsi
The highest catalytic efficiency is observed with arachidonate followed by (8S)-HPETE and(15S)-HPETE with similar efficiencies (PubMed:16112079). kcat is 0.22 sec(-1) for (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is 0.045 sec(-1) for (8Z,11Z,14Z)-eicosatrienoate (PubMed:27435673).2 Publications
- KM=1.2 µM for arachidonate (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=2.1 µM for (8S)-HPETE (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=5.7 µM for (8S)-HETE (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=39 µM for (15S)-HPETE (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=15 µM for (15S)-HETE (at pH 7.4 and 25 degrees Celsius)1 Publication
- KM=2.86 µM for (5Z,8Z,11Z,14Z)-eicosatetraenoate1 Publication
- KM=0.964 µM for (8Z,11Z,14Z)-eicosatrienoate1 Publication
: hydroperoxy eicosatetraenoic acid biosynthesis Pathwayi
This protein is involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis, which is part of Lipid metabolism.1 PublicationView all proteins of this organism that are known to be involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 15 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 17 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 39 | Calcium 2By similarity | 1 | |
Metal bindingi | 40 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 42 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 44 | Calcium 2By similarity | 1 | |
Metal bindingi | 86 | Calcium 1By similarity | 1 | |
Metal bindingi | 87 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 374 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 379 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 554 | Iron; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 677 | Iron; via carboxylate; catalyticPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- arachidonate 15-lipoxygenase activity Source: UniProtKB
- arachidonate 8(S)-lipoxygenase activity Source: UniProtKB
- calcium ion binding Source: MGI
- iron ion binding Source: MGI
- linoleate 13S-lipoxygenase activity Source: MGI
- linoleate 9S-lipoxygenase activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
- oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: GO_Central
GO - Biological processi
- arachidonic acid metabolic process Source: UniProtKB
- cannabinoid biosynthetic process Source: MGI
- endocannabinoid signaling pathway Source: MGI
- hepoxilin biosynthetic process Source: MGI
- linoleic acid metabolic process Source: UniProtKB
- lipid metabolic process Source: MGI
- lipid oxidation Source: GO_Central
- lipoxin A4 biosynthetic process Source: MGI
- lipoxygenase pathway Source: UniProtKB
- negative regulation of cell cycle Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of growth Source: MGI
- phospholipid metabolic process Source: UniProtKB
- positive regulation of chemokine production Source: MGI
- positive regulation of keratinocyte differentiation Source: UniProtKB
- positive regulation of macrophage derived foam cell differentiation Source: MGI
- positive regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Dioxygenase, Oxidoreductase |
Biological process | Lipid metabolism |
Ligand | Calcium, Iron, Lipid-binding, Metal-binding |
Enzyme and pathway databases
Reactomei | R-MMU-2142770, Synthesis of 15-eicosatetraenoic acid derivatives |
UniPathwayi | UPA00881 |
Chemistry databases
SwissLipidsi | SLP:000000650 SLP:000000742 |
Names & Taxonomyi
Protein namesi | Recommended name: Polyunsaturated fatty acid lipoxygenase ALOX8CuratedAlternative name(s): 15-lipoxygenase 2By similarity Short name: 15-LOX-2By similarity Arachidonate 15-lipoxygenase B Short name: 15-LOX-B Arachidonate 8S-lipoxygenase (EC:1.13.11.-1 Publication6 Publications) Short name: 8-LOX Short name: 8S-LOX Linoleate 9S-lipoxygenase ALOX8Curated (EC:1.13.11.581 Publication2 Publications) |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1098228, Alox8 |
Subcellular locationi
Cytosol
- cytosol By similarity
Other locations
- Membrane By similarity; Peripheral membrane protein By similarity
Note: Predominantly cytosolic; becomes enriched at membranes upon calcium binding.By similarity
Cytoskeleton
- cytoskeleton Source: MGI
Cytosol
- cytosol Source: UniProtKB
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- adherens junction Source: MGI
- extrinsic component of membrane Source: MGI
- focal adhesion Source: MGI
- membrane Source: MGI
Keywords - Cellular componenti
Cytoplasm, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 374 | H → L: Loss of enzymatic activity. 1 Publication | 1 | |
Mutagenesisi | 558 | S → A, H or N: Retains catalytic activity indicating it is not required for iron ligand-binding. 1 Publication | 1 | |
Mutagenesisi | 603 | Y → D: Changes the stereoselectivity of the oxygenation reaction to produce (15S)-HPETE instead of (8S)-HPETE. Completely changes the stereoselectivity; when associated with V-604. 1 Publication | 1 | |
Mutagenesisi | 604 | H → V: Changes the stereoselectivity of the oxygenation reaction to produce (15S)-HPETE instead of (8S)-HPETE. Completely changes the stereoselectivity; when associated with D-603. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220701 | 1 – 677 | Polyunsaturated fatty acid lipoxygenase ALOX8Add BLAST | 677 |
Proteomic databases
PaxDbi | O35936 |
PRIDEi | O35936 |
PTM databases
PhosphoSitePlusi | O35936 |
Expressioni
Tissue specificityi
Expressed in epidermis and brain (PubMed:9305900, PubMed:9518531). No expression found in heart, spleen, liver, skeletal muscle, kidney or testis.2 Publications
Inductioni
By phorbol ester.1 Publication
Gene expression databases
Bgeei | ENSMUSG00000020891, Expressed in skin of back and 72 other tissues |
ExpressionAtlasi | O35936, baseline and differential |
Genevisiblei | O35936, MM |
Interactioni
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000021262 |
Miscellaneous databases
RNActi | O35936, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2 – 125 | PLATPROSITE-ProRule annotationAdd BLAST | 124 | |
Domaini | 126 – 677 | LipoxygenasePROSITE-ProRule annotationAdd BLAST | 552 |
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
eggNOGi | ENOG502QVKD, Eukaryota |
GeneTreei | ENSGT00940000161510 |
HOGENOMi | CLU_004282_3_3_1 |
InParanoidi | O35936 |
OMAi | NPYAVRR |
OrthoDBi | 385042at2759 |
PhylomeDBi | O35936 |
TreeFami | TF105320 |
Family and domain databases
CDDi | cd01753, PLAT_LOX, 1 hit |
InterProi | View 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 IPR042062, PLAT_LOX_verte |
PANTHERi | PTHR11771, PTHR11771, 1 hit |
Pfami | View protein in Pfam PF00305, Lipoxygenase, 1 hit PF01477, PLAT, 1 hit |
PRINTSi | PR00087, LIPOXYGENASE PR00467, MAMLPOXGNASE |
SMARTi | View protein in SMART SM00308, LH2, 1 hit |
SUPFAMi | SSF48484, SSF48484, 1 hit SSF49723, SSF49723, 1 hit |
PROSITEi | View protein in PROSITE PS00711, LIPOXYGENASE_1, 1 hit PS00081, LIPOXYGENASE_2, 1 hit PS51393, LIPOXYGENASE_3, 1 hit PS50095, PLAT, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
O35936-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAKCRVRVST GEACGAGTWD KVSVSIVGTH GESPLVPLDH LGKEFSAGAE
60 70 80 90 100
EDFEVTLPQD VGTVLMLRVH KAPPEVSLPL MSFRSDAWFC RWFELEWLPG
110 120 130 140 150
AALHFPCYQW LEGAGELVLR EGAAKVSWQD HHPTLQDQRQ KELESRQKMY
160 170 180 190 200
SWKTYIEGWP RCLDHETVKD LDLNIKYSAM KNAKLFFKAH SAYTELKVKG
210 220 230 240 250
LLDRTGLWRS LREMRRLFNF RKTPAAEYVF AHWQEDAFFA SQFLNGINPV
260 270 280 290 300
LIRRCHSLPN NFPVTDEMVA PVLGPGTSLQ AELEKGSLFL VDHGILSGVH
310 320 330 340 350
TNILNGKPQF SAAPMTLLHQ SSGSGPLLPI AIQLKQTPGP DNPIFLPSDD
360 370 380 390 400
TWDWLLAKTW VRNSEFYIHE AVTHLLHAHL IPEVFALATL RQLPRCHPLF
410 420 430 440 450
KLLIPHIRYT LHINTLAREL LVAPGKLIDK STGLGTGGFS DLIKRNMEQL
460 470 480 490 500
NYSVLCLPED IRARGVEDIP GYYYRDDGMQ IWGAIKSFVS EIVSIYYPSD
510 520 530 540 550
TSVQDDQELQ AWVREIFSEG FLGRESSGMP SLLDTREALV QYITMVIFTC
560 570 580 590 600
SAKHAAVSSG QFDSCVWMPN LPPTMQLPPP TSKGQARPES FIATLPAVNS
610 620 630 640 650
SSYHIIALWL LSAEPGDQRP LGHYPDEHFT EDAPRRSVAA FQRKLIQISK
660 670
GIRERNRGLA LPYTYLDPPL IENSVSI
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB1ASX6 | B1ASX6_MOUSE | Polyunsaturated fatty acid lipoxyge... | Alox8 | 648 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural varianti | 32 | E → G in clone K12. | 1 | |
Natural varianti | 38 | L → M in clone G2. | 1 | |
Natural varianti | 58 | P → R in clone K12. | 1 | |
Natural varianti | 76 | V → A in clones G2, G5, G11 and K1. | 1 | |
Natural varianti | 413 | I → V in clone K7. | 1 | |
Natural varianti | 536 | R → Q in clones G2, G5 and G11. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U93277 mRNA Translation: AAC53356.1 Y14696 mRNA Translation: CAA75003.1 AK028724 mRNA Translation: BAC26085.1 AL645527 Genomic DNA No translation available. BC015253 mRNA Translation: AAH15253.1 |
CCDSi | CCDS24886.1 |
RefSeqi | NP_033791.1, NM_009661.4 |
Genome annotation databases
Ensembli | ENSMUST00000021262; ENSMUSP00000021262; ENSMUSG00000020891 |
GeneIDi | 11688 |
KEGGi | mmu:11688 |
UCSCi | uc007jpl.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U93277 mRNA Translation: AAC53356.1 Y14696 mRNA Translation: CAA75003.1 AK028724 mRNA Translation: BAC26085.1 AL645527 Genomic DNA No translation available. BC015253 mRNA Translation: AAH15253.1 |
CCDSi | CCDS24886.1 |
RefSeqi | NP_033791.1, NM_009661.4 |
3D structure databases
SMRi | O35936 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10090.ENSMUSP00000021262 |
Chemistry databases
SwissLipidsi | SLP:000000650 SLP:000000742 |
PTM databases
PhosphoSitePlusi | O35936 |
Proteomic databases
PaxDbi | O35936 |
PRIDEi | O35936 |
Protocols and materials databases
Antibodypediai | 12373, 274 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000021262; ENSMUSP00000021262; ENSMUSG00000020891 |
GeneIDi | 11688 |
KEGGi | mmu:11688 |
UCSCi | uc007jpl.1, mouse |
Organism-specific databases
CTDi | 11688 |
MGIi | MGI:1098228, Alox8 |
Phylogenomic databases
eggNOGi | ENOG502QVKD, Eukaryota |
GeneTreei | ENSGT00940000161510 |
HOGENOMi | CLU_004282_3_3_1 |
InParanoidi | O35936 |
OMAi | NPYAVRR |
OrthoDBi | 385042at2759 |
PhylomeDBi | O35936 |
TreeFami | TF105320 |
Enzyme and pathway databases
UniPathwayi | UPA00881 |
Reactomei | R-MMU-2142770, Synthesis of 15-eicosatetraenoic acid derivatives |
Miscellaneous databases
BioGRID-ORCSi | 11688, 2 hits in 17 CRISPR screens |
ChiTaRSi | Alox8, mouse |
PROi | PR:O35936 |
RNActi | O35936, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000020891, Expressed in skin of back and 72 other tissues |
ExpressionAtlasi | O35936, baseline and differential |
Genevisiblei | O35936, MM |
Family and domain databases
CDDi | cd01753, PLAT_LOX, 1 hit |
InterProi | View 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 IPR042062, PLAT_LOX_verte |
PANTHERi | PTHR11771, PTHR11771, 1 hit |
Pfami | View protein in Pfam PF00305, Lipoxygenase, 1 hit PF01477, PLAT, 1 hit |
PRINTSi | PR00087, LIPOXYGENASE PR00467, MAMLPOXGNASE |
SMARTi | View protein in SMART SM00308, LH2, 1 hit |
SUPFAMi | SSF48484, SSF48484, 1 hit SSF49723, SSF49723, 1 hit |
PROSITEi | View protein in PROSITE PS00711, LIPOXYGENASE_1, 1 hit PS00081, LIPOXYGENASE_2, 1 hit PS51393, LIPOXYGENASE_3, 1 hit PS50095, PLAT, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ALOX8_MOUSE | |
Accessioni | O35936Primary (citable) accession number: O35936 Secondary accession number(s): B1ASX5 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 11, 2001 |
Last sequence update: | January 1, 1998 | |
Last modified: | February 10, 2021 | |
This is version 170 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families