PTGIS (prostaglandin I2 (prostacyclin) synthase)
2009-05-01 Inês Cebola , Miguel A Peinado AffiliationInstitute of Predictive, Personalized Medicine of Cancer (IMPPC), Badalona, Barcelona, Spain
Identity
HGNC
LOCATION
20q13.13
IMAGE
LEGEND
Map of 20q13 chromosomal region.
LOCUSID
ALIAS
CYP8,CYP8A1,PGIS,PTGI
FUSION GENES
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.
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.
Proteins
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.
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
Entity name
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 name
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 name
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 name
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.
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 name
Cerebral infarction
Disease
Association between cerebral infarction and the PTGIS promoter VNTR alleles with less repeats.
Entity name
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 19276290 | 2009 | Common polymorphisms in the prostaglandin pathway genes and their association with breast cancer susceptibility and survival. | Abraham JE et al |
| 11780052 | 2001 | The DNA sequence and comparative analysis of human chromosome 20. | Deloukas P et al |
| 16007128 | 2005 | Hypermethylation of the prostacyclin synthase (PTGIS) promoter is a frequent event in colorectal cancer and associated with aneuploidy. | Frigola J et al |
| 8051072 | 1994 | Isolation and molecular cloning of prostacyclin synthase from bovine endothelial cells. | Hara S et al |
| 10577996 | 1999 | Human prostacyclin synthase gene and hypertension : the Suita Study. | Iwai N et al |
| 8185632 | 1994 | Molecular cloning and expression of human prostacyclin synthase. | Miyata A et al |
| 12372404 | 2002 | Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. | Nakayama T et al |
| 15136467 | 2004 | Prostacyclin in human non-small cell lung cancers. | Nana-Sinkam P et al |
| 16006589 | 2005 | Prostacyclin signaling in the kidney: implications for health and disease. | Nasrallah R et al |
| 17315398 | 2005 | Molecular mechanisms responsible for the antiinflammatory and protective effect of HDL on the endothelium. | Norata GD et al |
| 16537708 | 2006 | Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. | Poole EM et al |
| 18506748 | 2008 | 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 et al |
| 17374734 | 2007 | Genetic and epigenetic regulation of the human prostacyclin synthase promoter in lung cancer cell lines. | Stearman RS et al |
| 8831668 | 1996 | Organization of the gene encoding human prostacyclin synthase. | Wang LH et al |
| 8812456 | 1996 | Human gene encoding prostacyclin synthase (PTGIS): genomic organization, chromosomal localization, and promoter activity. | Yokoyama C et al |
Other Information
Locus ID:
NCBI: 5740
MIM: 601699
HGNC: 9603
Ensembl: ENSG00000124212
Variants:
dbSNP: 5740
ClinVar: 5740
TCGA: ENSG00000124212
COSMIC: PTGIS
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000124212 | ENST00000244043 | Q16647 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA166155905 | rs5629 | Variant | VipGene | associated | 17070428, 12040339 | ||
| PA443670 | Cerebral Infarction | Disease | VipGene | associated | |||
| PA444552 | Hypertension | Disease | VipGene | associated | |||
| PA445019 | Myocardial Infarction | Disease | VipGene | associated |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38639351 | 2024 | Identification of Prostaglandin I(2) Synthase Rare Variants in Patients With Williams Syndrome and Severe Peripheral Pulmonary Stenosis. | 0 |
| 38639351 | 2024 | Identification of Prostaglandin I(2) Synthase Rare Variants in Patients With Williams Syndrome and Severe Peripheral Pulmonary Stenosis. | 0 |
| 36703911 | 2023 | Effects of Lipid Metabolism-Related Genes PTGIS and HRASLS on Phenotype, Prognosis, and Tumor Immunity in Lung Squamous Cell Carcinoma. | 5 |
| 37258478 | 2023 | rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS. | 3 |
| 37779109 | 2023 | Validating the role of PTGIS gene in colorectal cancer by bioinformatics analysis and in vitro experiments. | 2 |
| 37796199 | 2023 | Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer. | 0 |
| 36703911 | 2023 | Effects of Lipid Metabolism-Related Genes PTGIS and HRASLS on Phenotype, Prognosis, and Tumor Immunity in Lung Squamous Cell Carcinoma. | 5 |
| 37258478 | 2023 | rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS. | 3 |
| 37779109 | 2023 | Validating the role of PTGIS gene in colorectal cancer by bioinformatics analysis and in vitro experiments. | 2 |
| 37796199 | 2023 | Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer. | 0 |
| 33527589 | 2021 | A new insight into subinteractomes of functional antagonists: Thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases. | 3 |
| 34155103 | 2021 | Reduced levels of prostaglandin I(2) synthase: a distinctive feature of the cancer-free trichothiodystrophy. | 8 |
| 33527589 | 2021 | A new insight into subinteractomes of functional antagonists: Thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases. | 3 |
| 34155103 | 2021 | Reduced levels of prostaglandin I(2) synthase: a distinctive feature of the cancer-free trichothiodystrophy. | 8 |
| 32236489 | 2020 | Association of Rare PTGIS Variants With Susceptibility and Pulmonary Vascular Response in Patients With Idiopathic Pulmonary Arterial Hypertension. | 20 |
Citation
Inês Cebola ; Miguel A Peinado
PTGIS (prostaglandin I2 (prostacyclin) synthase)
Atlas Genet Cytogenet Oncol Haematol. 2009-05-01
Online version: http://atlasgeneticsoncology.org/gene/44219/ptgis
