Prostaglandin G/H synthase 2

Prostaglandin G/H synthase 2

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 response11939906,16373578,19540099,22942274,26859324,27226593,7592599,7947975,9261177. 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 thromboxanes16373578,22942274,26859324,27226593,7592599,7947975,9261177. 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 electrons16373578,22942274,26859324,27226593,7592599,7947975,9261177. 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 prostaglandins11939906,19540099. In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids27642067. Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response22942274. 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 alcohols11034610,11192938,9048568,9261177. Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation12391014. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs)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-RvE221206090. 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 infection26236990. In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE)22068350,26282205. 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). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)

Quoted from UniProt’s FUNCTION annotation for P35354 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Vesicles
• Cytosoladditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Microsome membrane · Endoplasmic reticulum membrane · Nucleus inner membrane · Nucleus outer membrane

Expression by cell type

Single cell type RNA, the 8 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Neutrophils1,508.5 nCPM
• Epididymal basal cells666.1 nCPM
• monocytes659 nCPM
• Urothelial cells450.9 nCPM
• Mast cells391 nCPM
• Ocular epithelial cells381.7 nCPM
• Alveolar cells type 1296.2 nCPM
• Fibroblasts184.6 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

• urinary bladder151.3 nTPM
• seminal vesicle120.2 nTPM
• bone marrow110.4 nTPM