| Written | 2009-05 | Inês Cebola, Miguel A Peinado |
| Institute of Predictive, Personalized Medicine of Cancer (IMPPC), Badalona, Barcelona, Spain |
| Identity |
| Alias (NCBI) | CYP8 | CYP8A1 | EC 5.3.99.4 | MGC126858 | MGC126860 | PGIS | PTGI |
| HGNC (Hugo) | PTGIS |
| HGNC Alias symb | PGIS | CYP8A1 |
| HGNC Alias name | "cytochrome P450, family 8, subfamily A, polypeptide 1 | prostacyclin synthase" |
| HGNC Previous name | prostaglandin I2 (prostacyclin) synthase |
| LocusID (NCBI) | 5740 |
| Atlas_Id | 44219 |
| Location | 20q13.13 [Link to chromosome band 20q13] |
| Location_base_pair | Starts at 49503874 and ends at 49568137 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping PTGIS.png] |
 | |
| Map of 20q13 chromosomal region. | |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| PMEPA1 (20q13.31) / PTGIS (20q13.13) | RIMS2 (8q22.3) / PTGIS (20q13.13) |
| DNA/RNA |
 | |
| Schematic diagram of PTGIS genomic region. | |
| Description | 64297 bases (chr20:47553818-47618114); 10 exons; telomere to centromere orientation. |
| Transcription | Two alternative splicing products; 5624bp (coding, 1578bp ORF) and 313bp (non-coding). A 1.5kb upstream sequence presents CG-rich and pyrimidine-rich regions and contains consensus sequences for the recognition sites of Sp-1, AP-2, INF-gamma responsive element, GATA, NF-kB, glucocorticoid responsive element and a CACCC box. It has been demonstrated that PTGIS transcription is regulated via Sp1 binding, which may affected by polymorphisms in the promoter region. The CG-rich region presents significant promoter activity. |
| Protein |
| Description | PTGIS is a protein from the cytochrome P450 superfamily that consists of 500 amino acids and has a molecular weight of 57kDa. Is a single-pass membrane protein with a single transmembrane domain (1-20) and presents a heme-binding site at position 441. No post-translational modifications have been described for this protein. |
 | |
| PTGIS protein structure: secondary structure composition and features of interest. | |
| Expression | Abundant in heart, lung, skeletal muscle, ovary and prostate. PTGIS is found underexpressed in most colorectal carcinomas and in several lung carcinomas and hypertensive subjects. |
| Localisation | At cellular level can be found in the endoplasmatic reticulum membrane and in microsomes as a peripheral membrane protein. |
| Function | Catalyses the isomerization of prostaglandin H2 to prostacyclin (prostaglandin I2), a potent vasodilator and inhibitor of platelet aggregation. |
| Homology | Pan troglodytes - Prostaglandin I2 (prostacyclin) Synthase. Canis lupus familiaris - Prostaglandin I2 (prostacyclin) Synthase. Bos taurus - Prostaglandin I2 (prostacyclin) Synthase. Mus musculus - Prostaglandin I2 (prostacyclin) Synthase. Rattus norvegicus - Prostaglandin I2 (prostacyclin) Synthase. Danio rerio - Prostaglandin I2 (prostacyclin) Synthase like. |
| Mutations |
| Note | One splicing mutation has been associated with essential hypertension. |
| Implicated in |
| Note | |
| Entity | Colorectal cancer |
| Note | PTGIS promoter is silenced by through promoter hypermethylation in a large subset of colorectal carcinomas (also observed in colorectal adenomas and in several colorectal cancer cell lines). The PTGIS silencing is an early event on tumor progression and age and sex-independent. A PTGIS promoter VNTR polymorphism has been associated with the risk of colorectal polyps, being the risk increased when both alleles present less than 6 repeats. |
| Entity | Non-small cell lung cancer |
| Disease | PTGIS promoter is hypermethylated in lung cancer cell lines. The VNTR polymophism has also been associated with gene silencing in lung cancer cells. |
| Entity | Breast cancer |
| Disease | The combination of the SNPs PTGIS(11)rs477627, PTGIS(21)rs476496 and PTGIS(20)rs1066894, located in the 5' region and first intron, confers reduced susceptibility to breast cancer. |
| Entity | Essential hypertension |
| Disease | A splicing mutation (T->C at the +2 position of the donor site of the intron 9) alters the reading frame and results in the production of a truncated protein with the heme-binding region deleted. The subjects found with this mutation presented lower levels of prostacyclin and hypertension. The polymorphism C1117A has been significantly associated with hypertension, being the allele C associated with higher risk the condition, although it does not change the aminoacid sequence. A polymorphism in the 5' region with a variable number of repeats of a 9-bp sequence (CCGCCAGCC) is associated with hypertension. The alleles less repeats possess less Sp1 sites and present lower promoter activity, being related with higher pulse pressure in women and higher systolic blood pressure in older individuals. |
| Entity | Cerebral infarction |
| Disease | Association between cerebral infarction and the PTGIS promoter VNTR alleles with less repeats. |
| Entity | Myocardial infarction |
| Disease | A synonymous SNP at codon 373 (Arg373Arg) in exon 8 has been associated with risk of myocardial infarction in the japanese population. |
| Bibliography |
| Common polymorphisms in the prostaglandin pathway genes and their association with breast cancer susceptibility and survival. |
| Abraham JE, Harrington P, Driver KE, Tyrer J, Easton DF, Dunning AM, Pharoah PD. |
| Clin Cancer Res. 2009 Mar 15;15(6):2181-91. Epub 2009 Mar 10. |
| PMID 19276290 |
| The DNA sequence and comparative analysis of human chromosome 20. |
| Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J. |
| Nature. 2001 Dec 20-27;414(6866):865-71. |
| PMID 11780052 |
| Hypermethylation of the prostacyclin synthase (PTGIS) promoter is a frequent event in colorectal cancer and associated with aneuploidy. |
| Frigola J, Munoz M, Clark SJ, Moreno V, Capella G, Peinado MA. |
| Oncogene. 2005 Nov 10;24(49):7320-6. |
| PMID 16007128 |
| Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells. |
| Hara S, Miyata A, Yokoyama C, Inoue H, Brugger R, Lottspeich F, Ullrich V, Tanabe T. |
| J Biol Chem. 1994 Aug 5;269(31):19897-903. |
| PMID 8051072 |
| Human prostacyclin synthase gene and hypertension : the Suita Study. |
| Iwai N, Katsuya T, Ishikawa K, Mannami T, Ogata J, Higaki J, Ogihara T, Tanabe T, Baba S. |
| Circulation. 1999 Nov 30;100(22):2231-6. |
| PMID 10577996 |
| Molecular cloning and expression of human prostacyclin synthase. |
| Miyata A, Hara S, Yokoyama C, Inoue H, Ullrich V, Tanabe T. |
| Biochem Biophys Res Commun. 1994 May 16;200(3):1728-34. |
| PMID 8185632 |
| Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. |
| Nakayama T, Soma M, Watanabe Y, Hasimu B, Sato M, Aoi N, Kosuge K, Kanmatsuse K, Kokubun S, Marrow JD, Oates JA. |
| Biochem Biophys Res Commun. 2002 Oct 11;297(5):1135-9. |
| PMID 12372404 |
| Prostacyclin in human non-small cell lung cancers. |
| Nana-Sinkam P, Golpon H, Keith RL, Oyer RJ, Sotto-Santiago S, Moore MD, Franklin W, Nemenoff RA, Geraci MW. |
| Chest. 2004 May;125(5 Suppl):141S. |
| PMID 15136467 |
| Prostacyclin signaling in the kidney: implications for health and disease. |
| Nasrallah R, Hebert RL. |
| Am J Physiol Renal Physiol. 2005 Aug;289(2):F235-46. (REVIEW) |
| PMID 16006589 |
| Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. |
| Norata GD, Catapano AL. |
| Vasc Health Risk Manag. 2005;1(2):119-29. (REVIEW) |
| PMID 17315398 |
| Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. |
| Poole EM, Bigler J, Whitton J, Sibert JG, Potter JD, Ulrich CM. |
| Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):502-8. |
| PMID 16537708 |
| Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. |
| Scotto L, Narayan G, Nandula SV, Arias-Pulido H, Subramaniyam S, Schneider A, Kaufmann AM, Wright JD, Pothuri B, Mansukhani M, Murty VV. |
| Genes Chromosomes Cancer. 2008 Sep;47(9):755-65. |
| PMID 18506748 |
| Genetic and epigenetic regulation of the human prostacyclin synthase promoter in lung cancer cell lines. |
| Stearman RS, Grady MC, Nana-Sinkam P, Varella-Garcia M, Geraci MW. |
| Mol Cancer Res. 2007 Mar;5(3):295-308. |
| PMID 17374734 |
| Organization of the gene encoding human prostacyclin synthase. |
| Wang LH, Chen L. |
| Biochem Biophys Res Commun. 1996 Sep 24;226(3):631-7. |
| PMID 8831668 |
| Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity. |
| Yokoyama C, Yabuki T, Inoue H, Tone Y, Hara S, Hatae T, Nagata M, Takahashi EI, Tanabe T. |
| Genomics. 1996 Sep 1;36(2):296-304. |
| PMID 8812456 |
| Citation |
| This paper should be referenced as such : |
| Cebola, I ; Peinado, MA |
| PTGIS (prostaglandin I2 (prostacyclin) synthase) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(4):416-420. |
| Free journal version : [ pdf ] [ DOI ] |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ] |
|
t(8;20)(q22;q13) RIMS2/PTGIS
PMEPA1/PTGIS (20q13) |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Feb 19 17:58:24 CET 2021 |
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