UniProtKB - P51399 (LOX5_MESAU)
Polyunsaturated fatty acid 5-lipoxygenase
ALOX5
Functioni
Catalyzes the oxygenation of arachidonate to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation. Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene. Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (By similarity).
Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers. In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes. Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40. Also may play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK. Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).
By similarityCatalytic activityi
- EC:1.13.11.34By similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- (18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + O2 = (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 5-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
: leukotriene A4 biosynthesis Pathwayi
This protein is involved in the pathway leukotriene A4 biosynthesis, which is part of Lipid metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway leukotriene A4 biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 17 | Calcium 1; via carbonyl oxygen; structuralBy similarity | 1 | |
Metal bindingi | 18 | Calcium 2; via carbonyl oxygen; structuralBy similarity | 1 | |
Metal bindingi | 19 | Calcium 2; structuralBy similarity | 1 | |
Metal bindingi | 44 | Calcium 2; structuralBy similarity | 1 | |
Metal bindingi | 45 | Calcium 2; via carbonyl oxygen; structuralBy similarity | 1 | |
Metal bindingi | 47 | Calcium 2; structuralBy similarity | 1 | |
Metal bindingi | 79 | Calcium 1; via carbonyl oxygen; structuralBy similarity | 1 | |
Metal bindingi | 80 | Calcium 1; via carbonyl oxygen; structuralBy similarity | 1 | |
Sitei | 103 | Essential for stabilizing binding to COTL1By similarity | 1 | |
Metal bindingi | 367 | Iron; via tele nitrogen; catalyticPROSITE-ProRule annotationBy similarity | 1 | |
Metal bindingi | 372 | Iron; via tele nitrogen; catalyticPROSITE-ProRule annotationBy similarity | 1 | |
Metal bindingi | 550 | Iron; via tele nitrogen; catalyticPROSITE-ProRule annotationBy similarity | 1 | |
Metal bindingi | 554 | Iron; catalyticPROSITE-ProRule annotationBy similarity | 1 | |
Metal bindingi | 673 | Iron; via carbonyl oxygen; catalyticPROSITE-ProRule annotationBy similarity | 1 |
GO - Molecular functioni
- arachidonate 12(S)-lipoxygenase activity Source: RHEA
- arachidonate 5-lipoxygenase activity Source: UniProtKB
- arachidonate 8(S)-lipoxygenase activity Source: RHEA
- hydrolase activity Source: UniProtKB-KW
- iron ion binding Source: UniProtKB
GO - Biological processi
- dendritic cell migration Source: UniProtKB
- glucose homeostasis Source: UniProtKB
- humoral immune response Source: UniProtKB
- leukocyte chemotaxis involved in inflammatory response Source: UniProtKB
- leukocyte migration involved in inflammatory response Source: UniProtKB
- leukotriene A4 biosynthetic process Source: UniProtKB
- leukotriene biosynthetic process Source: UniProtKB
- lipoxin biosynthetic process Source: UniProtKB
- negative regulation of angiogenesis Source: UniProtKB
- negative regulation of endothelial cell proliferation Source: UniProtKB
- negative regulation of inflammatory response Source: UniProtKB
- negative regulation of response to endoplasmic reticulum stress Source: UniProtKB
- negative regulation of sprouting angiogenesis Source: UniProtKB
- negative regulation of vascular wound healing Source: UniProtKB
- negative regulation of wound healing Source: UniProtKB
- positive regulation of bone mineralization Source: UniProtKB
- positive regulation of leukocyte adhesion to arterial endothelial cell Source: UniProtKB
- regulation of cellular response to oxidative stress Source: UniProtKB
- regulation of cytokine production involved in inflammatory response Source: UniProtKB
- regulation of fat cell differentiation Source: UniProtKB
- regulation of inflammatory response Source: UniProtKB
- regulation of inflammatory response to wounding Source: UniProtKB
- regulation of insulin secretion Source: UniProtKB
- regulation of reactive oxygen species biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Dioxygenase, Hydrolase, Oxidoreductase |
Biological process | Leukotriene biosynthesis, Lipid metabolism |
Ligand | Calcium, Iron, Metal-binding |
Enzyme and pathway databases
UniPathwayi | UPA00877 |
Names & Taxonomyi
Protein namesi | Recommended name: Polyunsaturated fatty acid 5-lipoxygenaseBy similarity (EC:1.13.11.-By similarity)Alternative name(s): Arachidonate 5-lipoxygenaseBy similarity (EC:1.13.11.34By similarity) Short name: 5-LO1 Publication Short name: 5-lipoxygenase1 Publication |
Gene namesi | Name:ALOX5By similarity |
Organismi | Mesocricetus auratus (Golden hamster) |
Taxonomic identifieri | 10036 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Cricetidae › Cricetinae › Mesocricetus |
Proteomesi |
|
Subcellular locationi
Nucleus
- Nucleus matrix By similarity
- Nucleus membrane By similarity; Peripheral membrane protein By similarity
- Nucleus envelope By similarity
- Nucleus intermembrane space By similarity
Cytoplasm and Cytosol
Other locations
- perinuclear region By similarity
Note: Shuttles between cytoplasm and nucleus. Found exclusively in the nucleus, when phosphorylated on Ser-272. Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association.By similarity
Cytosol
- cytosol Source: UniProtKB
Nucleus
- nuclear envelope lumen Source: UniProtKB
- nuclear matrix Source: UniProtKB-SubCell
- nuclear membrane Source: UniProtKB
Other locations
- perinuclear region of cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Membrane, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000220694 | 1 – 673 | Polyunsaturated fatty acid 5-lipoxygenaseAdd BLAST | 673 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 271 | PhosphoserineBy similarity | 1 | |
Modified residuei | 523 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinInteractioni
Subunit structurei
Homodimer.
Interacts with ALOX5AP and LTC4S.
Interacts with COTL1, the interaction is required for stability and efficient catalytic activity.
Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS).
Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1.
By similarityProtein-protein interaction databases
STRINGi | 10036.XP_005066151.1 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2 – 117 | PLATPROSITE-ProRule annotationAdd BLAST | 116 | |
Domaini | 118 – 673 | LipoxygenasePROSITE-ProRule annotationAdd BLAST | 556 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | ENOG502QQSP, Eukaryota |
OrthoDBi | 385042at2759 |
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 |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MPSYTVTVAT GSQWFAGTDD YIYLSLIGSA GCSEKHLLDK AFYNDFERGA
60 70 80 90 100
VDSYDVTVDE ELGEIQLVRI EKRKYWLHDD WYLKYITLKT PTDYIEFPCY
110 120 130 140 150
RWITGEGEIV LRDGRAKLAR DDQIHILKQH RRKELEARQK QYRWMEWNPG
160 170 180 190 200
FPLSIDAKCH KDLPRDIQFD SEKGVDFVLN YSKAMENLFI NRFMHMFQSS
210 220 230 240 250
WNDFADFEKI FVKISNTISE RVKNHWQEDL MFGYQFLNGC NPVLIKRCRE
260 270 280 290 300
LPQKLPVTTE MVECSLERHL SLEQEVQEGN IFIVDYELLD GIDANKTDPC
310 320 330 340 350
THQFLAAPIC LLYKNLANKI VPIAIQLNQA PGEKNPIFLP SDAKYDWLLA
360 370 380 390 400
KIWVRSSDFH VHQTITHLLC THLVSEVFGI AMYRQLPAVH PIFKLLVAHV
410 420 430 440 450
RFTIAINTKA REQLICEYGL FDKANATGGG GHVQMVQRAV QDLTYSSLCF
460 470 480 490 500
PEAIKARGMD STEDIPYYFY RDDGLLVWEA IQSFTSEVVS IYYEDDQVVM
510 520 530 540 550
EDQELQDFVK DVYVYGMRGR KASGFPKSIK SREKLSEYLT VVIFTASAQH
560 570 580 590 600
AAVNFGQYDW CSWIPNAPPT MRAPPATAKG VVTIEQIVAT LPDRGRSCWH
610 620 630 640 650
LGAVWALSQF QENELFLGMY PEEHFIEKPV KEAMTRFRKN LEAIVNVIAE
660 670
RNKNKKLPYY YLSPDRIPNS VAI
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U43333 mRNA Translation: AAA85257.1 |
RefSeqi | NP_001268516.1, NM_001281587.1 |
Genome annotation databases
GeneIDi | 101839970 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U43333 mRNA Translation: AAA85257.1 |
RefSeqi | NP_001268516.1, NM_001281587.1 |
3D structure databases
SMRi | P51399 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10036.XP_005066151.1 |
Genome annotation databases
GeneIDi | 101839970 |
Organism-specific databases
CTDi | 240 |
Phylogenomic databases
eggNOGi | ENOG502QQSP, Eukaryota |
OrthoDBi | 385042at2759 |
Enzyme and pathway databases
UniPathwayi | UPA00877 |
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 |
MobiDBi | Search... |
Entry informationi
Entry namei | LOX5_MESAU | |
Accessioni | P51399Primary (citable) accession number: P51399 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | January 23, 2007 | |
Last modified: | September 29, 2021 | |
This is version 121 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families