Prostacyclin synthase

Prostaglandin-I synthase (EC 5.3.99.4) also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene.^[4] This enzyme belongs to the family of cytochrome P450 isomerases.

prostaglandin-I synthase
Cartoon diagram of human prostacyclin synthase. Heme group visible at center. From PDB: 2IAG​
Identifiers
EC no.	5.3.99.4
CAS no.	65802-86-0
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / QuickGO
Search PMC articles PubMed articles NCBI proteins

PTGIS
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3B6H, 2IAG
Identifiers
Aliases	PTGIS, CYP8, CYP8A1, PGIS, PTGI, prostaglandin I2 (prostacyclin) synthase, prostaglandin I2 synthase
External IDs	OMIM: 601699; MGI: 1097156; HomoloGene: 37374; GeneCards: PTGIS; OMA:PTGIS - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.13 Start 49,503,874 bp[1] End 49,568,137 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parietal pleura right coronary artery saphenous vein pericardium left uterine tube Descending thoracic aorta ascending aorta germinal epithelium left coronary artery vena cava n/a More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding isomerase activity metal ion binding monooxygenase activity protein binding heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen prostaglandin-I synthase activity Cellular component cytoplasm integral component of membrane endoplasmic reticulum membrane membrane caveola nucleus endoplasmic reticulum extracellular space Biological process prostaglandin metabolic process positive regulation of execution phase of apoptosis cellular response to interleukin-6 lipid metabolism icosanoid metabolic process cyclooxygenase pathway fatty acid metabolic process positive regulation of angiogenesis fatty acid biosynthetic process negative regulation of nitric oxide biosynthetic process decidualization cellular response to interleukin-1 positive regulation of peroxisome proliferator activated receptor signaling pathway apoptotic signaling pathway negative regulation of NF-kappaB transcription factor activity negative regulation of inflammatory response cellular response to hypoxia embryo implantation prostaglandin biosynthetic process NAD biosynthesis via nicotinamide riboside salvage pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5740 19223 Ensembl ENSG00000124212 n/a UniProt Q16647 O35074 RefSeq (mRNA) NM_000961 NM_008968 RefSeq (protein) NP_000952 NP_032994 Location (UCSC) Chr 20: 49.5 – 49.57 Mb n/a PubMed search [2] [3]
Wikidata
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Function

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. However, this protein is considered a member of the cytochrome P450 superfamily on the basis of sequence similarity rather than functional similarity. This endoplasmic reticulum membrane protein catalyzes the conversion of prostaglandin H₂ to prostacyclin (prostaglandin I₂), a potent vasodilator and inhibitor of platelet aggregation. An imbalance of prostacyclin and its physiological antagonist thromboxane A₂ contribute to the development of myocardial infarction, stroke, and atherosclerosis.^[5]

Unlike most P450 enzymes, PGIS does not require molecular oxygen (O₂). Instead it uses its heme cofactor to catalyze the isomerization of prostaglandin H₂ to prostacyclin. Prostaglandin H₂ is produced by cyclooxygenase in the first committed step of prostaglandin biosynthesis.

Nomenclature

The systematic name of this enzyme class is (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate 6-isomerase. Other names in common use include prostacyclin synthase, prostacyclin synthetase, prostagladin I₂ synthetase, PGI₂ synthase, PGIS, PTGIS, and PGI₂ synthetase.

Pathways

Thromboxane synthesis

Eicosanoid synthesis.

Molecular interactions

Generally, protein–protein interactions play crucial roles and are critical for formation of protein microenvironment, cell signaling and direct regulation of the activity of metabolic enzymes. Information on tissue-specific spectrum of molecular interactions of prostacyclin synthase will be useful for subnetwork analysis of PTGIS. Following proteins became known as potential direct binders of PTGIS: CYP2J2, GST, GSTA1, GLRX3, AKR1A1. Protein–protein and protein-peptide interactions were experimentally verified using surface plasmon resonance technology.^[6]

See also

• Prostanoid