UniProtKB - O19183 (PGH2_HORSE)
Prostaglandin G/H synthase 2
PTGS2
Functioni
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate, with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins. In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids. Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response. Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols. Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection. In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE).
By similarityMiscellaneous
Catalytic activityi
- EC:1.14.99.1By similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphoethanolamine + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-phosphoethanolamineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-(prostaglandin G2)-sn-glycero-3-phosphoethanolamine + AH2 = 2-(prostaglandin H2)-sn-glycero-3-phosphoethanolamine + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + 2 O2 = 2-(prostaglandin G2)-sn-glycero-3-phosphocholineBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-(prostaglandin G2)-sn-glycero-3-phosphocholine + AH2 = 2-(prostaglandin H2)-sn-glycero-3-phosphocholine + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 = (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + AH2 + O2 = 2-[(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-glycero-3-phosphocholine + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + AH2 + O2 = 2-[(15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-sn-glycero-3-phosphocholine + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + AH2 + O2 = 2-[(11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoyl]-sn-glycero-3-phosphocholine + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (15R)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (11R)-hydroxy-(5Z,8Z,12E,14Z)-eicosatetraenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (11R)-hydroxy-(5Z,8Z,12E,14Z,17Z)-eicosapentaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15R)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + AH2 + O2 = (15S)-hydroxy-(5Z,8Z,11Z,13E,17Z)-eicosapentaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + AH2 + O2 = 13R-hydroxy-(7Z,10Z,14E,16Z,19Z)-docosapentaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 13-hydroxy-(4Z,7Z,10Z,14E,16Z,19Z)-docosahexaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,15R)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + AH2 + O2 = 17R-hydroxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + AH2 + O2 = (5S,11R)-dihydroxy-(6E,8Z,12E,14Z)-eicosatetraenoate + A + H2OBy similarityThis reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 11R-hydroperoxy-(5Z,8Z,12E,14Z)-eicosatetraenoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
: prostaglandin biosynthesis Pathwayi
This protein is involved in the pathway prostaglandin biosynthesis, which is part of Lipid metabolism.By similarityView all proteins of this organism that are known to be involved in the pathway prostaglandin biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 106 | SubstrateBy similarity | 1 | |
Active sitei | 193 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Binding sitei | 341 | SubstrateBy similarity | 1 | |
Active sitei | 371 | For cyclooxygenase activityBy similarity | 1 | |
Metal bindingi | 374 | Iron (heme axial ligand)PROSITE-ProRule annotation | 1 | |
Sitei | 516 | Aspirin-acetylated serineBy similarity | 1 |
GO - Molecular functioni
- heme binding Source: UniProtKB
- metal ion binding Source: UniProtKB-KW
- oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen Source: GO_Central
- peroxidase activity Source: UniProtKB-KW
- prostaglandin-endoperoxide synthase activity Source: UniProtKB
GO - Biological processi
- cyclooxygenase pathway Source: UniProtKB
- inflammatory response Source: InterPro
- prostaglandin biosynthetic process Source: UniProtKB
- regulation of blood pressure Source: UniProtKB
- regulation of neuroinflammatory response Source: UniProtKB
- response to oxidative stress Source: InterPro
Keywordsi
Molecular function | Dioxygenase, Oxidoreductase, Peroxidase |
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
UniPathwayi | UPA00662 |
Protein family/group databases
PeroxiBasei | 4123, EcabPGHS02 |
Names & Taxonomyi
Protein namesi | Recommended name: Prostaglandin G/H synthase 2 (EC:1.14.99.1)Alternative name(s): Cyclooxygenase-2 Short name: COX-2 PHS II Prostaglandin H2 synthase 2 Short name: PGH synthase 2 Short name: PGHS-2 Prostaglandin-endoperoxide synthase 2 |
Gene namesi | Name:PTGS2 Synonyms:COX2 |
Organismi | Equus caballus (Horse) |
Taxonomic identifieri | 9796 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Perissodactyla › Equidae › Equus › |
Proteomesi |
|
Subcellular locationi
Nucleus
- Nucleus inner membrane By similarity; Peripheral membrane protein By similarity
- Nucleus outer membrane By similarity; Peripheral membrane protein By similarity
Endoplasmic reticulum
- Microsome membrane By similarity; Peripheral membrane protein By similarity
- Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity
Note: Detected on the lumenal side of the endoplasmic reticulum and nuclear envelope.By similarity
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB-SubCell
Nucleus
- nuclear inner membrane Source: UniProtKB
- nuclear outer membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- neuron projection Source: GO_Central
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, Microsome, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | By similarityAdd BLAST | 17 | |
ChainiPRO_0000023874 | 18 – 604 | Prostaglandin G/H synthase 2Add BLAST | 587 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 21 ↔ 32 | By similarity | ||
Disulfide bondi | 22 ↔ 145 | By similarity | ||
Disulfide bondi | 26 ↔ 42 | By similarity | ||
Disulfide bondi | 44 ↔ 54 | By similarity | ||
Glycosylationi | 53 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 130 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 396 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 526 | S-nitrosocysteineBy similarity | 1 | |
Disulfide bondi | 555 ↔ 561 | By similarity | ||
Glycosylationi | 580 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, S-nitrosylationProteomic databases
PaxDbi | O19183 |
Expressioni
Gene expression databases
Bgeei | ENSECAG00000017181, Expressed in chorionic villus and 21 other tissues |
Interactioni
Subunit structurei
Homodimer.
By similarityProtein-protein interaction databases
STRINGi | 9796.ENSECAP00000015107 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 18 – 55 | EGF-likePROSITE-ProRule annotationAdd BLAST | 38 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
HOGENOMi | CLU_022428_0_0_1 |
InParanoidi | O19183 |
OMAi | PTYNVHY |
OrthoDBi | 324380at2759 |
TreeFami | TF329675 |
Family and domain databases
Gene3Di | 1.10.640.10, 1 hit |
InterProi | View protein in InterPro IPR029576, COX-2 IPR000742, EGF-like_dom IPR019791, Haem_peroxidase_animal IPR010255, Haem_peroxidase_sf IPR037120, Haem_peroxidase_sf_animal |
PANTHERi | PTHR11903:SF8, PTHR11903:SF8, 1 hit |
Pfami | View protein in Pfam PF03098, An_peroxidase, 2 hits PF00008, EGF, 1 hit |
PRINTSi | PR00457, ANPEROXIDASE |
SUPFAMi | SSF48113, SSF48113, 1 hit |
PROSITEi | View protein in PROSITE PS50026, EGF_3, 1 hit PS50292, PEROXIDASE_3, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MLARALLLCV ALALGHAANP CCSNPCQNRG VCMSVGFDQY QCDCTRTGFY
60 70 80 90 100
GENCSTPEFL TRIKLFLKPT PNTVHYILTH FKGVWNIVNS FPFLRNAVMK
110 120 130 140 150
YVLVSRSHLI ESPPTYNAQY GYKSWESFSN LSYYTRALPP VADGCPTPMG
160 170 180 190 200
VKGKKELPDS KEIVEKFLLR RKFIPDPQGT NMMFAFFAQH FTHQFFKTDP
210 220 230 240 250
KRGPAFTKGL GHGVDLSHIY GETLDRQHKL RLFKDGKMKY QIINGEVYPP
260 270 280 290 300
TVKDTQVEMI YPPHIPEHLR FAVGQEVFGL VPGLMMYATI WLREHNRVCD
310 320 330 340 350
VLKQEHPEWD DERLFQTSRL ILIGETIKIV IEDYVQHLSG YHFKLKFDPE
360 370 380 390 400
LLFNQQFQYQ NRIAAEFNTL YHWHPLLPDT FQIDDQEYNF QQFLYNNSIL
410 420 430 440 450
LEHGLTQFVE SFSRQIAGRV AGGRNVPAAA QKIAKASIDQ SREMKYQSLN
460 470 480 490 500
EYRKRFRLTP YKSFEELTGE KEMAAELEAL YGDIDAMELY PALLVEKPRP
510 520 530 540 550
DAIFGETMVE LGAPFSLKGL LGNPICSPDY WKPSTFGGEV GFKIINTASI
560 570 580 590 600
QSLICNNVKG CPFTAFSVQD PQLSKAVTIN ASASHSGLDD VNPTVLLKER
STEL
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF027335 Genomic DNA Translation: AAC48808.1 AF027334 mRNA Translation: AAC07911.1 |
RefSeqi | NP_001075244.1, NM_001081775.2 |
Genome annotation databases
GeneIDi | 791253 |
KEGGi | ecb:791253 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF027335 Genomic DNA Translation: AAC48808.1 AF027334 mRNA Translation: AAC07911.1 |
RefSeqi | NP_001075244.1, NM_001081775.2 |
3D structure databases
SMRi | O19183 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9796.ENSECAP00000015107 |
Protein family/group databases
PeroxiBasei | 4123, EcabPGHS02 |
Proteomic databases
PaxDbi | O19183 |
Genome annotation databases
GeneIDi | 791253 |
KEGGi | ecb:791253 |
Organism-specific databases
CTDi | 5743 |
Phylogenomic databases
HOGENOMi | CLU_022428_0_0_1 |
InParanoidi | O19183 |
OMAi | PTYNVHY |
OrthoDBi | 324380at2759 |
TreeFami | TF329675 |
Enzyme and pathway databases
UniPathwayi | UPA00662 |
Gene expression databases
Bgeei | ENSECAG00000017181, Expressed in chorionic villus and 21 other tissues |
Family and domain databases
Gene3Di | 1.10.640.10, 1 hit |
InterProi | View protein in InterPro IPR029576, COX-2 IPR000742, EGF-like_dom IPR019791, Haem_peroxidase_animal IPR010255, Haem_peroxidase_sf IPR037120, Haem_peroxidase_sf_animal |
PANTHERi | PTHR11903:SF8, PTHR11903:SF8, 1 hit |
Pfami | View protein in Pfam PF03098, An_peroxidase, 2 hits PF00008, EGF, 1 hit |
PRINTSi | PR00457, ANPEROXIDASE |
SUPFAMi | SSF48113, SSF48113, 1 hit |
PROSITEi | View protein in PROSITE PS50026, EGF_3, 1 hit PS50292, PEROXIDASE_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PGH2_HORSE | |
Accessioni | O19183Primary (citable) accession number: O19183 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 15, 1998 |
Last sequence update: | January 1, 1998 | |
Last modified: | February 23, 2022 | |
This is version 156 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
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families