prostacyclin synthase

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.{{cite web | title = Entrez Gene: PTGIS | url =https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5740 }}

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.

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.

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.{{cite journal | vauthors = Ershov PV, Mezentsev YV, Kopylov AT, Yablokov EO, Svirid AV, Lushchyk AY, Kaluzhskiy LA, Gilep AA, Usanov SA, Medvedev AE, Ivanov AS | title = Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome | journal = Biology | volume = 8 | issue = 2 | pages = 49 | date = June 2019 | pmid = 31226805 | pmc = 6628129 | doi = 10.3390/biology8020049 | doi-access = free }}

• Prostanoid

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• {{cite journal | vauthors = DeWitt DL, Smith WL | title = Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. Evidence that the enzyme is a hemoprotein | journal = The Journal of Biological Chemistry | volume = 258 | issue = 5 | pages = 3285–3293 | date = March 1983 | pmid = 6338016 | doi = 10.1016/S0021-9258(18)32859-X | doi-access = free }}
• {{cite journal | vauthors = Ullrich V, Castle L, Weber P | title = Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase | journal = Biochemical Pharmacology | volume = 30 | issue = 14 | pages = 2033–2036 | date = July 1981 | pmid = 7023490 | doi = 10.1016/0006-2952(81)90218-5 }}
• {{cite journal | vauthors = Xie X, Ma YT, Fu ZY, Yang YN, Wang YH, Chen BD, Liu F | title = [Study on the association of cyclooxygenase-2 -765g>C and prostacyclin synthase C1117A polymorphisms and the risk of myocardial infarction in Uigur population of Xinjiang, China] | journal = Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi | volume = 29 | issue = 6 | pages = 598–603 | date = June 2008 | pmid = 19040046 }}
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• {{cite journal | vauthors = Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Wang YH, Chen BD, Liu F | title = [Association of GLu461ALa polymorphism of prostacyclin synthase gene with myocardial infarction in Uigur population] | journal = Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine] | volume = 43 | issue = 3 | pages = 237–241 | date = March 2009 | pmid = 19534932 }}
• {{cite journal | vauthors = Yoshida T, Kato K, Fujimaki T, Yokoi K, Oguri M, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nishigaki Y, Tanaka M, Nozawa Y, Yamada Y | title = Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome | journal = Genomics | volume = 93 | issue = 3 | pages = 221–226 | date = March 2009 | pmid = 19056482 | doi = 10.1016/j.ygeno.2008.11.001 | doi-access = free }}
• {{cite journal | vauthors = Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, Caprau D, Zimmerman CR, Steffen KM, Johnson KJ, Marazita ML, Murray JC | title = Determination of genetic predisposition to patent ductus arteriosus in preterm infants | journal = Pediatrics | volume = 123 | issue = 4 | pages = 1116–1123 | date = April 2009 | pmid = 19336370 | pmc = 2734952 | doi = 10.1542/peds.2008-0313 }}
• {{cite journal | vauthors = Xie X, Ma Y, Fu Z, Yang Y, Wang Y, Chen B, Liu F | title = [Association of polymorphism of the prostacyclin synthase gene with myocardial infarction in Uigur population of Xinjiang] | journal = Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics | volume = 25 | issue = 6 | pages = 708–711 | date = December 2008 | pmid = 19065539 }}
• {{cite journal | vauthors = Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW | title = Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants | journal = Pharmacogenetics | volume = 14 | issue = 1 | pages = 1–18 | date = January 2004 | pmid = 15128046 | doi = 10.1097/00008571-200401000-00001 }}
• {{cite journal | vauthors = Barbalić M, Narancić NS, Skarić-Jurić T, Salihović MP, Klarić IM, Lauc LB, Janićijević B, Farrall M, Rudan I, Campbell H, Wright AF, Hastie ND, Rudan P | title = A quantitative trait locus for SBP maps near KCNB1 and PTGIS in a population isolate | journal = American Journal of Hypertension | volume = 22 | issue = 6 | pages = 663–668 | date = June 2009 | pmid = 19265782 | doi = 10.1038/ajh.2009.46 | doi-access = free }}
• {{cite journal | vauthors = Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Chen BD, Wang YH, Liu F | title = Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction | journal = Clinical Chemistry and Laboratory Medicine | volume = 47 | issue = 3 | pages = 347–352 | year = 2009 | pmid = 19327107 | doi = 10.1515/CCLM.2009.078 | s2cid = 30117064 }}
• {{cite journal | vauthors = Abraham JE, Harrington P, Driver KE, Tyrer J, Easton DF, Dunning AM, Pharoah PD | title = Common polymorphisms in the prostaglandin pathway genes and their association with breast cancer susceptibility and survival | journal = Clinical Cancer Research | volume = 15 | issue = 6 | pages = 2181–2191 | date = March 2009 | pmid = 19276290 | doi = 10.1158/1078-0432.CCR-08-0716 | doi-access = free }}
• {{cite journal | vauthors = Ruan KH, Wu J, Cervantes V | title = Characterization of the substrate mimic bound to engineered prostacyclin synthase in solution using high-resolution NMR spectroscopy and mutagenesis: implication of the molecular mechanism in biosynthesis of prostacyclin | journal = Biochemistry | volume = 47 | issue = 2 | pages = 680–688 | date = January 2008 | pmid = 18081314 | doi = 10.1021/bi701671q }}
• {{cite journal | vauthors = Hashimoto K, Ishibashi K, Gebretsadik T, Hartert TV, Yamamoto A, Nakayama T, Ohashi K, Sakata H, Kawasaki Y, Katayose M, Sakuma H, Suzuki H, Hosoya M, Peebles RS, Suzutani T | title = Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children | journal = Journal of Medical Virology | volume = 80 | issue = 11 | pages = 2015–2022 | date = November 2008 | pmid = 18814254 | doi = 10.1002/jmv.21318 | s2cid = 6010576 }}
• {{cite journal | vauthors = Ma YT, Fu ZY, Yang YN, Chen BD, Wang YH | title = Haplotype analysis of the CYP8A1 gene associated with myocardial infarction | journal = Clinical and Applied Thrombosis/Hemostasis | volume = 15 | issue = 5 | pages = 574–580 | date = October 2009 | pmid = 19147528 | doi = 10.1177/1076029608329581 | s2cid = 20352085 | doi-access = free }}
• {{cite journal | vauthors = Lemaitre RN, Rice K, Marciante K, Bis JC, Lumley TS, Wiggins KL, Smith NL, Heckbert SR, Psaty BM | title = Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke | journal = Atherosclerosis | volume = 204 | issue = 2 | pages = e58–e63 | date = June 2009 | pmid = 19046748 | pmc = 2753183 | doi = 10.1016/j.atherosclerosis.2008.10.011 }}
• {{cite journal | vauthors = Ito T, Okada T, Mimuro J, Miyashita H, Uchibori R, Urabe M, Mizukami H, Kume A, Takahashi M, Ikeda U, Sakata Y, Shimada K, Ozawa K | title = Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats | journal = Hypertension | volume = 50 | issue = 3 | pages = 531–536 | date = September 2007 | pmid = 17635855 | doi = 10.1161/HYPERTENSIONAHA.107.091348 | doi-access = free }}
• {{cite journal | vauthors = Ma YT, Xie X, Fu ZY, Yang YN, Ma X, Wang YH, Chen BD, Liu F | title = [Haplotypes analysis of the prostacyclin synthase gene and myocardial infarction in Uigur population] | journal = Zhonghua Xin Xue Guan Bing Za Zhi | volume = 37 | issue = 2 | pages = 115–119 | date = February 2009 | pmid = 19719985 }}
• {{cite journal | vauthors = Yeh HC, Gerfen GJ, Wang JS, Tsai AL, Wang LH | title = Characterization of the peroxidase mechanism upon reaction of prostacyclin synthase with peracetic acid. Identification of a tyrosyl radical intermediate | journal = Biochemistry | volume = 48 | issue = 5 | pages = 917–928 | date = February 2009 | pmid = 19187034 | pmc = 2849756 | doi = 10.1021/bi801382v }}
• {{cite journal | vauthors = Young RP, Hopkins RJ, Hay BA, Epton MJ, Mills GD, Black PN, Gardner HD, Sullivan R, Gamble GD | title = A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers | journal = Postgraduate Medical Journal | volume = 85 | issue = 1008 | pages = 515–524 | date = October 2009 | pmid = 19789190 | doi = 10.1136/pgmj.2008.077107 | doi-access = free }}

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• {{MeshName|prostacyclin+synthetase}}

{{NLM content}}

{{Cytochrome P450}}

{{Metabolism of complex lipids}}

{{Prostanoid signaling modulators}}

{{Intramolecular oxidoreductases}}

{{Enzymes}}

{{Portal bar|Biology|border=no}}

Category:EC 5.3.99

Category:Heme enzymes

Category:Enzymes of known structure