Prostacyclin synthase

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
View/Edit Human View/Edit Mouse

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.

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

References

1. GRCh38: Ensembl release 89: ENSG00000124212 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Yokoyama C, Yabuki T, Inoue H, Tone Y, Hara S, Hatae T, et al. (September 1996). "Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity". Genomics. 36 (2): 296–304. doi:10.1006/geno.1996.0465. PMID   8812456.
5. "Entrez Gene: PTGIS".
6. Ershov PV, Mezentsev YV, Kopylov AT, Yablokov EO, Svirid AV, Lushchyk AY, et al. (June 2019). "Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome". Biology. 8 (2): 49. doi: 10.3390/biology8020049 . PMC   6628129 . PMID   31226805.

Further reading

• DeWitt DL, Smith WL (March 1983). "Purification of prostacyclin synthase from bovine aorta by immunoaffinity chromatography. Evidence that the enzyme is a hemoprotein". The Journal of Biological Chemistry. 258 (5): 3285–3293. doi: 10.1016/S0021-9258(18)32859-X . PMID   6338016.
• Ullrich V, Castle L, Weber P (July 1981). "Spectral evidence for the cytochrome P450 nature of prostacyclin synthetase". Biochemical Pharmacology. 30 (14): 2033–2036. doi:10.1016/0006-2952(81)90218-5. PMID   7023490.
• Xie X, Ma YT, Fu ZY, Yang YN, Wang YH, Chen BD, et al. (June 2008). "[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]". Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. 29 (6): 598–603. PMID   19040046.
• Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, et al. (August 2009). "Association of genetic variants with chronic kidney disease in individuals with different lipid profiles". International Journal of Molecular Medicine. 24 (2): 233–246. doi: 10.3892/ijmm_00000226 . PMID   19578796.
• Palmieri RT, Wilson MA, Iversen ES, Clyde MA, Calingaert B, Moorman PG, et al. (December 2008). "Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women". Cancer Epidemiology, Biomarkers & Prevention. 17 (12): 3567–3572. doi:10.1158/1055-9965.EPI-08-0548. PMC   2664299 . PMID   19064572.
• Mavaddat N, Dunning AM, Ponder BA, Easton DF, Pharoah PD (January 2009). "Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer". Cancer Epidemiology, Biomarkers & Prevention. 18 (1): 255–259. doi:10.1158/1055-9965.EPI-08-0704. PMC   2655077 . PMID   19124506.
• Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Wang YH, et al. (March 2009). "[Association of GLu461ALa polymorphism of prostacyclin synthase gene with myocardial infarction in Uigur population]". Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine]. 43 (3): 237–241. PMID   19534932.
• Yoshida T, Kato K, Fujimaki T, Yokoi K, Oguri M, Watanabe S, et al. (March 2009). "Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome". Genomics. 93 (3): 221–226. doi: 10.1016/j.ygeno.2008.11.001 . PMID   19056482.
• Dagle JM, Lepp NT, Cooper ME, Schaa KL, Kelsey KJ, Orr KL, et al. (April 2009). "Determination of genetic predisposition to patent ductus arteriosus in preterm infants". Pediatrics. 123 (4): 1116–1123. doi:10.1542/peds.2008-0313. PMC   2734952 . PMID   19336370.
• Xie X, Ma Y, Fu Z, Yang Y, Wang Y, Chen B, et al. (December 2008). "[Association of polymorphism of the prostacyclin synthase gene with myocardial infarction in Uigur population of Xinjiang]". Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. 25 (6): 708–711. PMID   19065539.
• Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (January 2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics. 14 (1): 1–18. doi:10.1097/00008571-200401000-00001. PMID   15128046.
• Barbalić M, Narancić NS, Skarić-Jurić T, Salihović MP, Klarić IM, Lauc LB, et al. (June 2009). "A quantitative trait locus for SBP maps near KCNB1 and PTGIS in a population isolate". American Journal of Hypertension. 22 (6): 663–668. doi: 10.1038/ajh.2009.46 . PMID   19265782.
• Xie X, Ma YT, Fu ZY, Yang YN, Ma X, Chen BD, et al. (2009). "Association of polymorphisms of PTGS2 and CYP8A1 with myocardial infarction". Clinical Chemistry and Laboratory Medicine. 47 (3): 347–352. doi:10.1515/CCLM.2009.078. PMID   19327107. S2CID   30117064.
• Abraham JE, Harrington P, Driver KE, Tyrer J, Easton DF, Dunning AM, et al. (March 2009). "Common polymorphisms in the prostaglandin pathway genes and their association with breast cancer susceptibility and survival". Clinical Cancer Research. 15 (6): 2181–2191. doi: 10.1158/1078-0432.CCR-08-0716 . PMID   19276290.
• Ruan KH, Wu J, Cervantes V (January 2008). "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". Biochemistry. 47 (2): 680–688. doi:10.1021/bi701671q. PMID   18081314.
• Hashimoto K, Ishibashi K, Gebretsadik T, Hartert TV, Yamamoto A, Nakayama T, et al. (November 2008). "Functional polymorphism of the promoter region of the prostacyclin synthase gene and severity of RSV infection in hospitalized children". Journal of Medical Virology. 80 (11): 2015–2022. doi:10.1002/jmv.21318. PMID   18814254. S2CID   6010576.
• Ma YT, Fu ZY, Yang YN, Chen BD, Wang YH (October 2009). "Haplotype analysis of the CYP8A1 gene associated with myocardial infarction". Clinical and Applied Thrombosis/Hemostasis. 15 (5): 574–580. doi: 10.1177/1076029608329581 . PMID   19147528. S2CID   20352085.
• Lemaitre RN, Rice K, Marciante K, Bis JC, Lumley TS, Wiggins KL, et al. (June 2009). "Variation in eicosanoid genes, non-fatal myocardial infarction and ischemic stroke". Atherosclerosis. 204 (2): e58 –e63. doi:10.1016/j.atherosclerosis.2008.10.011. PMC   2753183 . PMID   19046748.
• Ito T, Okada T, Mimuro J, Miyashita H, Uchibori R, Urabe M, et al. (September 2007). "Adenoassociated virus-mediated prostacyclin synthase expression prevents pulmonary arterial hypertension in rats". Hypertension. 50 (3): 531–536. doi: 10.1161/HYPERTENSIONAHA.107.091348 . PMID   17635855.
• Ma YT, Xie X, Fu ZY, Yang YN, Ma X, Wang YH, et al. (February 2009). "[Haplotypes analysis of the prostacyclin synthase gene and myocardial infarction in Uigur population]". Zhonghua Xin Xue Guan Bing Za Zhi. 37 (2): 115–119. PMID   19719985.
• Yeh HC, Gerfen GJ, Wang JS, Tsai AL, Wang LH (February 2009). "Characterization of the peroxidase mechanism upon reaction of prostacyclin synthase with peracetic acid. Identification of a tyrosyl radical intermediate". Biochemistry. 48 (5): 917–928. doi:10.1021/bi801382v. PMC   2849756 . PMID   19187034.
• Young RP, Hopkins RJ, Hay BA, Epton MJ, Mills GD, Black PN, et al. (October 2009). "A gene-based risk score for lung cancer susceptibility in smokers and ex-smokers". Postgraduate Medical Journal. 85 (1008): 515–524. doi: 10.1136/pgmj.2008.077107 . PMID   19789190.

External links

• prostacyclin+synthetase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.