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Prostacyclin synthase

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Enzyme found in humans
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
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
Search
PMCarticles
PubMedarticles
NCBIproteins
PTGIS
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

3B6H, 2IAG

Identifiers
AliasesPTGIS, CYP8, CYP8A1, PGIS, PTGI, prostaglandin I2 (prostacyclin) synthase, prostaglandin I2 synthase
External IDsOMIM: 601699; MGI: 1097156; HomoloGene: 37374; GeneCards: PTGIS; OMA:PTGIS - orthologs
Gene location (Human)
Chromosome 20 (human)
Chr.Chromosome 20 (human)
Chromosome 20 (human)Genomic location for PTGISGenomic location for PTGIS
Band20q13.13Start49,503,874 bp
End49,568,137 bp
RNA expression pattern
Bgee
HumanMouse (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
Cellular component
Biological process
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
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 Mbn/a
PubMed search
Wikidata
View/Edit HumanView/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. 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.

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.

See also

References

  1. ^ GRCh38: Ensembl release 89: ENSG00000124212Ensembl, 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, Nagata M, Takahashi EI, Tanabe T (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, Pavel V.; Mezentsev, Yuri V.; Kopylov, Arthur T.; Yablokov, Evgeniy O.; Svirid, Andrey V.; Lushchyk, Aliaksandr Ya.; Kaluzhskiy, Leonid A.; Gilep, Andrei A.; Usanov, Sergey A.; Medvedev, Alexey E.; Ivanov, Alexis S. (2019-06-20). "Affinity Isolation and Mass Spectrometry Identification of Prostacyclin Synthase (PTGIS) Subinteractome". Biology. 8 (2): 49. doi:10.3390/biology8020049. ISSN 2079-7737. PMC 6628129. PMID 31226805.

Further reading

External links

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

Cytochromes, oxygenases: cytochrome P450 (Most belong to EC 1.14)
CYP1
CYP2
CYP3 (CYP3A)
CYP4
CYP5-20
CYP21-49
CYP51-69
CYP71-99
CYP101-281
CYP301-499
CYP501-699
CYP701-999
Metabolism: lipid metabolismeicosanoid metabolism enzymes
Precursor
Prostanoids
Leukotrienes
Ungrouped
Prostanoid signaling modulators
Receptor
(ligands)
DP (D2)Tooltip Prostaglandin D2 receptor
DP1Tooltip Prostaglandin D2 receptor 1
DP2Tooltip Prostaglandin D2 receptor 2
EP (E2)Tooltip Prostaglandin E2 receptor
EP1Tooltip Prostaglandin EP1 receptor
EP2Tooltip Prostaglandin EP2 receptor
EP3Tooltip Prostaglandin EP3 receptor
EP4Tooltip Prostaglandin EP4 receptor
Unsorted
FP (F)Tooltip Prostaglandin F receptor
IP (I2)Tooltip Prostacyclin receptor
TP (TXA2)Tooltip Thromboxane receptor
Unsorted
Enzyme
(inhibitors)
COX
(PTGS)
PGD2STooltip Prostaglandin D synthase
PGESTooltip Prostaglandin E synthaseHQL-79
PGFSTooltip Prostaglandin F synthaseBimatoprost
PGI2STooltip Prostacyclin synthaseTranylcypromine
TXASTooltip Thromboxane A synthase
Others
See also
Receptor/signaling modulators
Leukotriene signaling modulators
Isomerases: intramolecular oxidoreductases (EC 5.3)
5.3.1: Aldoses/Ketoses
5.3.2: Keto/Enol
5.3.3: C = C
5.3.4: S-S
5.3.99: other
Enzymes
Activity
Regulation
Classification
Kinetics
Types
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