Detail Information for IndEnz0018000799
IED ID IndEnz0018000799
Enzyme Type ID peroxidase000799
Protein Name Prostaglandin G/H synthase 1
EC 1.14.99.1
Cyclooxygenase-1
COX-1
Prostaglandin H2 synthase 1
PGH synthase 1
PGHS-1
PHS 1
Prostaglandin-endoperoxide synthase 1
Gene Name PTGS1 COX1
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MSRSLLLWFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTRTGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRSNLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRFLLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQYQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLYATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKFDPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEALVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQELVGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICSPEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL
Enzyme Length 599
Uniprot Accession Number P23219
Absorption
Active Site ACT_SITE 206; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; ACT_SITE 384; /note=For cyclooxygenase activity; /evidence=ECO:0000250
Activity Regulation ACTIVITY REGULATION: The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac and diclofenac. {ECO:0000269|PubMed:7947975}.
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + AH2 + 2 O2 = A + H2O + prostaglandin H2; Xref=Rhea:RHEA:23728, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:32395, ChEBI:CHEBI:57405; EC=1.14.99.1; Evidence={ECO:0000269|PubMed:7947975};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23729; Evidence={ECO:0000305|PubMed:7947975}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = prostaglandin G2; Xref=Rhea:RHEA:42596, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:82629; Evidence={ECO:0000269|PubMed:7947975};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42597; Evidence={ECO:0000305|PubMed:7947975}; CATALYTIC ACTIVITY: Reaction=AH2 + prostaglandin G2 = A + H2O + prostaglandin H2; Xref=Rhea:RHEA:42600, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499, ChEBI:CHEBI:57405, ChEBI:CHEBI:82629; Evidence={ECO:0000269|PubMed:7947975};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42601; Evidence={ECO:0000305|PubMed:7947975};
DNA Binding
EC Number 1.14.99.1
Enzyme Function FUNCTION: 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 (PubMed:7947975). Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable). {ECO:0000269|PubMed:7947975, ECO:0000305|PubMed:10966456, ECO:0000305|PubMed:24605250}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Lipid metabolism; prostaglandin biosynthesis. {ECO:0000269|PubMed:7947975}.
nucleotide Binding
Features Active site (2); Alternative sequence (5); Beta strand (19); Chain (1); Disulfide bond (5); Domain (1); Glycosylation (3); Helix (30); Metal binding (1); Mutagenesis (1); Natural variant (10); Sequence conflict (4); Signal peptide (1); Site (1); Turn (8)
Keywords 3D-structure;Alternative splicing;Dioxygenase;Disulfide bond;EGF-like domain;Endoplasmic reticulum;Fatty acid biosynthesis;Fatty acid metabolism;Glycoprotein;Heme;Iron;Lipid biosynthesis;Lipid metabolism;Membrane;Metal-binding;Microsome;Oxidoreductase;Peroxidase;Prostaglandin biosynthesis;Prostaglandin metabolism;Reference proteome;Signal
Interact With Q9NP61; P48645; P53801; Q8WZ73-3
Induction
Subcellular Location SUBCELLULAR LOCATION: Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein.
Modified Residue
Post Translational Modification
Signal Peptide SIGNAL 1..23
Structure 3D X-ray crystallography (1)
Cross Reference PDB 6Y3C;
Mapped Pubmed ID 11809691; 11877441; 11897504; 11920472; 11981837; 12050227; 12193665; 12213900; 12237309; 12242329; 12519124; 12545150; 12665651; 12711701; 12711844; 12720297; 12730088; 12835322; 12842195; 1380156; 14507922; 14625295; 14988266; 15041270; 15086459; 15159324; 15167967; 15190260; 15301234; 15328521; 15361066; 15375804; 15453269; 15504548; 15607906; 15654517; 15705965; 15720413; 15870920; 15963707; 16055872; 16105649; 16115753; 16150050; 16181776; 16323955; 16344721; 16411757; 16493486; 16678543; 16787416; 16857763; 16875891; 16930602; 17062130; 17071117; 17078001; 17130490; 17264103; 17301694; 17320986; 17322116; 17355643; 17495879; 17559347; 17624243; 17631383; 17640058; 17671743; 17673564; 17681165; 17868881; 17977913; 18173552; 18214026; 18280718; 18287876; 18459455; 18511850; 18571838; 18582172; 18612540; 18618313; 18636124; 18657230; 18676680; 18705313; 18753249; 18818748; 18838483; 18992148; 18997734; 19019335; 19046748; 19056482; 19060633; 19091535; 19124506; 19132198; 19132974; 19170196; 19205707; 19235530; 19258012; 19276290; 19282863; 19336370; 19350112; 19390185; 19399588; 19433337; 19527514; 19530321; 19625176; 19692168; 19723114; 19740098; 19769727; 19887674; 19913121; 19948975; 20225218; 20227045; 20227521; 20382140; 20437058; 20452482; 20453000; 20467438; 20530583; 20538124; 20628086; 20628624; 20673868; 20691446; 20720307; 21094252; 21097517; 21256536; 21266582; 21301321; 21351261; 21434767; 21478098; 21561892; 21699462; 21812955; 22049022; 22397921; 22609818; 22758658; 22860421; 22940005; 22972377; 22982857; 23029430; 23038044; 23074965; 23242413; 23597562; 23660496; 23668350; 23677911; 23886173; 23985963; 24008976; 24022467; 24022862; 24171795; 24244288; 24254970; 24333447; 24370448; 24535852; 24651623; 24758697; 24930730; 25339146; 25398544; 25645360; 25721048; 25906828; 25972361; 25988363; 26067486; 26081267; 26245672; 26339385; 26562384; 26672987; 26703471; 26748901; 26870959; 27060751; 27129261; 27318652; 27401285; 27522738; 27548026; 28244682; 28431615; 28708434; 29225187; 30240925; 30312731; 30320345; 30760327; 31339092; 31552592; 31734845; 31735164; 31760051; 32131611; 32171274; 32299908; 32584621; 33326144; 33450390; 33619313; 33800915; 4514999; 4521806; 4776443; 7552725; 8121489; 8175750; 9139685;
Motif
Gene Encoded By
Mass 68,686
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=5.1 uM for arachidonate {ECO:0000269|PubMed:7947975};
Metal Binding METAL 387; /note=Iron (heme b axial ligand); /evidence=ECO:0000255|PROSITE-ProRule:PRU00298
Rhea ID RHEA:23728; RHEA:23729; RHEA:42596; RHEA:42597; RHEA:42600; RHEA:42601
Cross Reference Brenda 1.14.99.1;