PTGS2
Description
The PTGS2 (prostaglandin-endoperoxide synthase 2) is a protein-coding gene located on chromosome 1.
Cyclooxygenase-2 (COX-2), also known as Prostaglandin-endoperoxide synthase 2 (HUGO PTGS2), is an enzyme that in humans is encoded by the PTGS2 gene. In humans it is one of three cyclooxygenases. It is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of prostacyclin, which is expressed in inflammation.
== Function == PTGS2 (COX-2), converts arachidonic acid (AA) to prostaglandin endoperoxide H2. PTGSs are targets for NSAIDs and PTGS2 (COX-2) specific inhibitors called coxibs. PTGS-2 is a sequence homodimer. Each monomer of the enzyme has a peroxidase and a PTGS (COX) active site. The PTGS (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins in two steps. First, hydrogen is abstracted from carbon 13 of arachidonic acid, and then two molecules of oxygen are added by the PTGS2 (COX-2), giving PGG2. Second, PGG2 is reduced to PGH2 in the peroxidase active site.
PTGS2 (also known as COX-2) is a dual cyclooxygenase and peroxidase enzyme that plays a crucial role in the biosynthesis of prostanoids, a class of C20 oxylipins mainly derived from arachidonate. PTGS2 catalyzes the conversion of arachidonate to prostaglandin G2 (PGG2) through oxygenation, followed by the reduction of PGG2 to prostaglandin H2 (PGH2) through peroxidase activity. PGH2 acts as the precursor for all 2-series prostaglandins and thromboxanes. PTGS2 also catalyzes the conversion of dihomo-gamma-linoleate and eicosapentaenoate to corresponding PGH1 and PGH3, precursors of 1- and 3-series prostaglandins, respectively. In an alternative prostanoid biosynthesis pathway, PTGS2 converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are further hydrolyzed by phospholipases to release free prostanoids. PTGS2 metabolizes 2-arachidonoyl glycerol to produce the glyceryl ester of PGH2, potentially contributing to pain response. PTGS2 generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism, oxygenating PUFAs to hydroperoxy compounds and reducing them to corresponding alcohols. PTGS2 is involved in the generation of resolvins during both sterile and infectious inflammation. It metabolizes docosahexaenoate to 17R-HDHA, a precursor of D-series resolvins. PTGS2 also contributes to the biosynthesis of E-series resolvins by converting eicosapentaenoate to 18S-HEPE, which is further metabolized to 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, PTGS2 converts docosapentaenoate to 13R-HDPA, a precursor for 13-series resolvins. In activated leukocytes, PTGS2 participates in the oxygenation of hydroxyeicosatetraenoates to diHETES. PTGS2 can utilize linoleate as a substrate and produce hydroxyoctadecadienoates. During neuroinflammation, PTGS2 plays a role in the neuronal secretion of specialized preresolving mediators, including 15R-lipoxin A4, which regulates phagocytic microglia. PTGS2 exists as a homodimer. {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: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:7947975, ECO:0000269|PubMed:9048568, ECO:0000269|PubMed:9261177, ECO:0000303|PubMed:19540099}
PTGS2 is also known as COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2, hCox-2.
