PTGS2
entrez
5743
canonical
uniprot
P35354
canonical
ensembl
ENSG00000073756
resolver
ensp
ENSP00000356438
resolver
ensp
ENSP00000506242
resolver
enst
ENST00000367468
resolver
enst
ENST00000680451
resolver
genesymbol
PTGS2
resolver
genesymbol_syn
COX2
resolver
hgnc
HGNC:9605
resolver
uniprot
A8K802
resolver
uniprot
Q16876
resolver
uniprot_entry
PGH2_HUMAN
resolver
uniprot_sec
A8K802
resolver
uniprot_sec
Q16876
resolver
activity_regulation
ACTIVITY REGULATION: The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, flurbiprofen, celecoxib, flufenamic, mefenamic and tolfenamic acids as well as by hydroperoxide scavenger erythrocyte glutathione peroxidase GPX1 (PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:9048568). Aspirin triggers enzyme acetylation turning off its ability to generate pro-inflammatory prostaglandins, but switches on its capacity to produce anti-inflammatory lipid mediators involved in inflammation resolution (PubMed:11034610, PubMed:12391014). Aspirin enhances lipoxygenase-type activity toward production of epimers with R stereochemistry such as 15R-HETE, 18R-HEPE, 15R-HEPE and 17R-HDHA (PubMed:11034610, PubMed:11192938, PubMed:12391014, PubMed:21206090, PubMed:22068350, PubMed:9048568). Atorvastatin, a cholesterol-lowering drug, triggers enzyme S-nitrosylation increasing production of 13-series resolvins (RvTs) (PubMed:26236990). {ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:12391014, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:22068350, ECO:0000269|PubMed:26236990, ECO:0000269|PubMed:9048568}.
uniprot
proteins
amino_acid_sequence
MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFLTRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADYGYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGSNMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKYQIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCDVLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQNRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRVAGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEALYGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEVGFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKERSTEL
uniprot
proteins
ec_number
1.14.99.1
uniprot
proteins
function
FUNCTION: Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:17519235, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). 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:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins respectively, though arachidonate (AA, C20:4(n-6)) remains the preferred substrate (PubMed:11939906, PubMed:17519235, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophospholipids to prostanoid lysophospholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). 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 (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). 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 (PubMed:21206090). 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 (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity) (PubMed:7642610). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity). {ECO:0000250|UniProtKB:P79208, ECO:0000250|UniProtKB:Q05769, ECO:0000269|PubMed:11034610, ECO:0000269|PubMed:11192938, ECO:0000269|PubMed:11939906, ECO:0000269|PubMed:12391014, ECO:0000269|PubMed:16373578, ECO:0000269|PubMed:17519235, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:22068350, ECO:0000269|PubMed:22942274, ECO:0000269|PubMed:26236990, ECO:0000269|PubMed:26282205, ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593, ECO:0000269|PubMed:27642067, ECO:0000269|PubMed:7592599, ECO:0000269|PubMed:7642610, ECO:0000269|PubMed:7947975, ECO:0000269|PubMed:9048568, ECO:0000269|PubMed:9261177, ECO:0000303|PubMed:19540099}.
uniprot
proteins
mass_dalton
68996
uniprot
proteins
mutagenesis
MUTAGEN 189; /note="Q->N: Increases two-electron hydroperoxide reduction. Has no effect on cyclooxygenase activity."; /evidence="ECO:0000269|PubMed:9261177"; MUTAGEN 189; /note="Q->R: Impairs two-electron hydroperoxide reduction and cyclooxygenase activity."; /evidence="ECO:0000269|PubMed:9261177"; MUTAGEN 189; /note="Q->V: Impairs two-electron hydroperoxide reduction."; /evidence="ECO:0000269|PubMed:9261177"; MUTAGEN 193; /note="H->A: Reduces two-electron hydroperoxide reduction and cyclooxygenase activity. Catalyzes predominantly one-electron hydroperoxide reduction."; /evidence="ECO:0000269|PubMed:9261177"; MUTAGEN 371; /note="Y->A: Decreased protein stability. Increased decrease of protein stability; when associated with A-516."; /evidence="ECO:0000269|PubMed:27226593"; MUTAGEN 516; /note="S->A: No effect on protein stability. Increased decrease of protein stability; when associated with A-371."; /evidence="ECO:0000269|PubMed:27226593"; MUTAGEN 516; /note="S->T: Decreased enzyme activity with arachidonic acid. Loss of cyclooxygenase activity; when associated with V-519."; /evidence="ECO:0000269|PubMed:26859324"; MUTAGEN 519; /note="G->V: Loss of cyclooxygenase activity. Loss of cyclooxygenase activity; when associated with T-516."; /evidence="ECO:0000269|PubMed:26859324"; MUTAGEN 526; /note="C->S: Prevents activation by nitric oxid (NO)."; /evidence="ECO:0000269|PubMed:16373578"; MUTAGEN 555; /note="C->S: Abolishes enzyme activity."; /evidence="ECO:0000269|PubMed:16373578"; MUTAGEN 561; /note="C->S: Does not affect activation by nitric oxid (NO)."; /evidence="ECO:0000269|PubMed:16373578
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; prostaglandin biosynthesis. {ECO:0000269|PubMed:26859324, ECO:0000269|PubMed:27226593}.
uniprot
proteins
post_translational_modification
PTM: S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526. {ECO:0000269|PubMed:16373578}.; PTM: Acetylated at Ser-565 by SPHK1. During neuroinflammation, acetylation by SPHK1 promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia. {ECO:0000250|UniProtKB:Q05769}.
uniprot
proteins
protein_family
Prostaglandin G/H synthase family
uniprot
proteins
pubmed
10966456
uniprot
proteins
pubmed
11034610
uniprot
proteins
pubmed
11192938
uniprot
proteins
pubmed
11939906
uniprot
proteins
pubmed
12391014
uniprot
proteins
pubmed
1380156
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15308583
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16373578
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17113084
uniprot
proteins
pubmed
17519235
uniprot
proteins
pubmed
19540099
uniprot
proteins
pubmed
21206090
uniprot
proteins
pubmed
22068350
uniprot
proteins
pubmed
22942274
uniprot
proteins
pubmed
24605250
uniprot
proteins
pubmed
26236990
uniprot
proteins
pubmed
26282205
uniprot
proteins
pubmed
26859324
uniprot
proteins
pubmed
27226593
uniprot
proteins
pubmed
27642067
uniprot
proteins
pubmed
27710942
uniprot
proteins
pubmed
7592599
uniprot
proteins
pubmed
7642610
uniprot
proteins
pubmed
7945196
uniprot
proteins
pubmed
7947975
uniprot
proteins
pubmed
8181472
uniprot
proteins
pubmed
8473346
uniprot
proteins
pubmed
9048568
uniprot
proteins
pubmed
9261177
uniprot
proteins
pubmed
9545330
uniprot
proteins
sequence_length
604
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Microsome membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Nucleus inner membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Nucleus outer membrane {ECO:0000269|PubMed:9545330}; Peripheral membrane protein. Note=Detected on the lumenal side of the endoplasmic reticulum and nuclear envelope. {ECO:0000269|PubMed:9545330}.
uniprot
proteins