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UniProtKB - Q16647 (PTGIS_HUMAN)
Protein
Prostacyclin synthase
Gene
PTGIS
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes the biosynthesis and metabolism of eicosanoids. Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2), a potent mediator of vasodilation and inhibitor of platelet aggregation (PubMed:18032380, PubMed:25623425, PubMed:12372404, PubMed:15115769).
Additionally, displays dehydratase activity, toward hydroperoxyeicosatetraenoates (HPETEs), especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) (PubMed:17459323).
5 PublicationsCatalytic activityi
- EC:5.3.99.43 PublicationsThis reaction proceeds in the forward3 Publications direction.
- EC:4.2.1.1521 PublicationThis reaction proceeds in the forward1 Publication direction.
- (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O1 PublicationThis reaction proceeds in the forward1 Publication direction.
- (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 = (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + A + H2O1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
heme2 Publications
Kineticsi
- KM=9.55 µM for 6-keto-PGF1alpha1 Publication
- KM=30 µM for prostaglandin H21 Publication
- KM=60 µM for (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate1 Publication
- KM=13 µM for prostaglandin H2 (at 23 degrees Celsius)1 Publication
- Vmax=534 mmol/min/pg enzyme with prostaglandin H2 as substrate1 Publication
- Vmax=15 µmol/min/mg enzyme with prostaglandin H2 as substrate1 Publication
- Vmax=980 mol/min/mol enzyme with prostaglandin H2 as substrate1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 106 | SubstrateBy similarity | 1 | |
Binding sitei | 112 | Substrate; via amide nitrogenBy similarity | 1 | |
Binding sitei | 287 | SubstrateBy similarity | 1 | |
Binding sitei | 382 | SubstrateBy similarity | 1 | |
Metal bindingi | 441 | Iron (heme axial ligand)Combined sources2 Publications | 1 |
GO - Molecular functioni
- heme binding Source: UniProtKB
- hydroperoxy icosatetraenoate dehydratase activity Source: UniProtKB-EC
- iron ion binding Source: InterPro
- monooxygenase activity Source: InterPro
- oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen Source: InterPro
- prostaglandin-I synthase activity Source: UniProtKB
GO - Biological processi
- apoptotic signaling pathway Source: UniProtKB
- cellular response to hypoxia Source: UniProtKB
- cellular response to interleukin-1 Source: UniProtKB
- cellular response to interleukin-6 Source: UniProtKB
- cyclooxygenase pathway Source: Reactome
- icosanoid metabolic process Source: UniProtKB
- NAD biosynthesis via nicotinamide riboside salvage pathway Source: Reactome
- negative regulation of inflammatory response Source: UniProtKB
- negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
- negative regulation of nitric oxide biosynthetic process Source: UniProtKB
- positive regulation of angiogenesis Source: UniProtKB
- positive regulation of execution phase of apoptosis Source: UniProtKB
- positive regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
- prostaglandin biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Isomerase, Lyase |
Biological process | Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BRENDAi | 5.3.99.4, 2681 |
PathwayCommonsi | Q16647 |
Reactomei | R-HSA-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-HSA-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-HSA-193807, Synthesis of bile acids and bile salts via 27-hydroxycholesterol R-HSA-197264, Nicotinamide salvaging R-HSA-211979, Eicosanoids R-HSA-211994, Sterols are 12-hydroxylated by CYP8B1 R-HSA-2162123, Synthesis of Prostaglandins (PG) and Thromboxanes (TX) |
SABIO-RKi | Q16647 |
SignaLinki | Q16647 |
Chemistry databases
SwissLipidsi | SLP:000001097 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:PTGIS Synonyms:CYP8, CYP8A1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:9603, PTGIS |
MIMi | 601699, gene |
neXtProti | NX_Q16647 |
VEuPathDBi | HostDB:ENSG00000124212 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Single-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB
Extracellular region or secreted
- extracellular space Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- caveola Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 1 – 20 | HelicalSequence analysisAdd BLAST | 20 |
Keywords - Cellular componenti
Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Essential hypertension (EHT)1 Publication
The disease may be caused by variants affecting the gene represented in this entry.
Disease descriptionA condition in which blood pressure is consistently higher than normal with no identifiable cause.
Related information in OMIMMutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 441 | C → H: Abolishes prostaglandin-I synthase activity. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 5740 |
MalaCardsi | PTGIS |
MIMi | 145500, phenotype |
OpenTargetsi | ENSG00000124212 |
Orphaneti | 243761, NON RARE IN EUROPE: Essential hypertension |
PharmGKBi | PA292 |
Miscellaneous databases
Pharosi | Q16647, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4428 |
DrugBanki | DB08675, (5Z)-7-{(1R,4S,5R,6R)-6-[(1E)-1-Octen-1-yl]-2,3-diazabicyclo[2.2.1]hept-2-en-5-yl}-5-heptenoic acid DB01240, Epoprostenol DB00812, Phenylbutazone |
DrugCentrali | Q16647 |
GuidetoPHARMACOLOGYi | 1356 |
Genetic variation databases
BioMutai | PTGIS |
DMDMi | 2493373 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000051910 | 1 – 500 | Prostacyclin synthaseAdd BLAST | 500 |
Proteomic databases
EPDi | Q16647 |
jPOSTi | Q16647 |
MassIVEi | Q16647 |
MaxQBi | Q16647 |
PaxDbi | Q16647 |
PeptideAtlasi | Q16647 |
PRIDEi | Q16647 |
ProteomicsDBi | 60999 |
PTM databases
CarbonylDBi | Q16647 |
iPTMneti | Q16647 |
PhosphoSitePlusi | Q16647 |
Expressioni
Tissue specificityi
Widely expressed; particularly abundant in ovary, heart, skeletal muscle, lung and prostate.1 Publication
Gene expression databases
Bgeei | ENSG00000124212, Expressed in parietal pleura and 212 other tissues |
Genevisiblei | Q16647, HS |
Organism-specific databases
HPAi | ENSG00000124212, Tissue enhanced (endometrium, fallopian tube, urinary bladder) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 111712, 5 interactors |
IntActi | Q16647, 1 interactor |
STRINGi | 9606.ENSP00000244043 |
Chemistry databases
BindingDBi | Q16647 |
Miscellaneous databases
RNActi | Q16647, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | Q16647 |
SMRi | Q16647 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16647 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 358 – 359 | Substrate bindingBy similarity | 2 |
Sequence similaritiesi
Belongs to the cytochrome P450 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00940000153709 |
HOGENOMi | CLU_018012_1_3_1 |
InParanoidi | Q16647 |
OMAi | EPQKYKY |
OrthoDBi | 454773at2759 |
PhylomeDBi | Q16647 |
TreeFami | TF105090 |
Family and domain databases
DisProti | DP02578 |
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR024204, Cyt_P450_CYP7A1-type IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf IPR027286, PTGIS |
PANTHERi | PTHR24306:SF4, PTHR24306:SF4, 1 hit |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PIRSFi | PIRSF000047, Cytochrome_CYPVIIA1, 1 hit PIRSF500628, PTGIS, 1 hit |
PRINTSi | PR00465, EP450IV |
SUPFAMi | SSF48264, SSF48264, 1 hit |
i Sequence
Sequence statusi: Complete.
Q16647-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAWAALLGLL AALLLLLLLS RRRTRRPGEP PLDLGSIPWL GYALDFGKDA
60 70 80 90 100
ASFLTRMKEK HGDIFTILVG GRYVTVLLDP HSYDAVVWEP RTRLDFHAYA
110 120 130 140 150
IFLMERIFDV QLPHYSPSDE KARMKLTLLH RELQALTEAM YTNLHAVLLG
160 170 180 190 200
DATEAGSGWH EMGLLDFSYS FLLRAGYLTL YGIEALPRTH ESQAQDRVHS
210 220 230 240 250
ADVFHTFRQL DRLLPKLARG SLSVGDKDHM CSVKSRLWKL LSPARLARRA
260 270 280 290 300
HRSKWLESYL LHLEEMGVSE EMQARALVLQ LWATQGNMGP AAFWLLLFLL
310 320 330 340 350
KNPEALAAVR GELESILWQA EQPVSQTTTL PQKVLDSTPV LDSVLSESLR
360 370 380 390 400
LTAAPFITRE VVVDLAMPMA DGREFNLRRG DRLLLFPFLS PQRDPEIYTD
410 420 430 440 450
PEVFKYNRFL NPDGSEKKDF YKDGKRLKNY NMPWGAGHNH CLGRSYAVNS
460 470 480 490 500
IKQFVFLVLV HLDLELINAD VEIPEFDLSR YGFGLMQPEH DVPVRYRIRP
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_010915 | 38 | P → L in allele CYP8A1*2. 1 PublicationCorresponds to variant dbSNP:rs1173082660Ensembl. | 1 | |
Natural variantiVAR_010916 | 118 | S → R in allele CYP8A1*3. 1 PublicationCorresponds to variant dbSNP:rs5622Ensembl. | 1 | |
Natural variantiVAR_014634 | 154 | E → A. Corresponds to variant dbSNP:rs5623Ensembl. | 1 | |
Natural variantiVAR_014635 | 171 | F → L. Corresponds to variant dbSNP:rs5624Ensembl. | 1 | |
Natural variantiVAR_014636 | 236 | R → C. Corresponds to variant dbSNP:rs5626EnsemblClinVar. | 1 | |
Natural variantiVAR_010917 | 379 | R → S in allele CYP8A1*4. 1 PublicationCorresponds to variant dbSNP:rs56195291Ensembl. | 1 | |
Natural variantiVAR_073186 | 447 | A → T in allele CYP8A1*5; results in a significantly decreased enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs146531327Ensembl. | 1 | |
Natural variantiVAR_014637 | 500 | P → S. Corresponds to variant dbSNP:rs5584Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D38145 mRNA Translation: BAA07343.1 AF297048 mRNA Translation: AAG31781.1 AF297049 mRNA Translation: AAG31782.1 AF297050 mRNA Translation: AAG31783.1 AF297051 mRNA Translation: AAG31784.1 AF297052 mRNA Translation: AAG31785.1 AL118525 Genomic DNA No translation available. BC101809 mRNA Translation: AAI01810.1 BC101811 mRNA Translation: AAI01812.1 |
CCDSi | CCDS13419.1 |
PIRi | JC2231 |
RefSeqi | NP_000952.1, NM_000961.3 |
Genome annotation databases
Ensembli | ENST00000244043.5; ENSP00000244043.3; ENSG00000124212.6 |
GeneIDi | 5740 |
KEGGi | hsa:5740 |
MANE-Selecti | ENST00000244043.5; ENSP00000244043.3; NM_000961.4; NP_000952.1 |
UCSCi | uc002xut.4, human |
Similar proteinsi
Cross-referencesi
Web resourcesi
PharmVar Pharmacogen Variation Consortium CYP8A1 alleles |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | D38145 mRNA Translation: BAA07343.1 AF297048 mRNA Translation: AAG31781.1 AF297049 mRNA Translation: AAG31782.1 AF297050 mRNA Translation: AAG31783.1 AF297051 mRNA Translation: AAG31784.1 AF297052 mRNA Translation: AAG31785.1 AL118525 Genomic DNA No translation available. BC101809 mRNA Translation: AAI01810.1 BC101811 mRNA Translation: AAI01812.1 |
CCDSi | CCDS13419.1 |
PIRi | JC2231 |
RefSeqi | NP_000952.1, NM_000961.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2IAG | X-ray | 2.15 | A/B | 23-500 | [»] | |
3B6H | X-ray | 1.62 | A/B | 18-500 | [»] | |
AlphaFoldDBi | Q16647 | |||||
SMRi | Q16647 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111712, 5 interactors |
IntActi | Q16647, 1 interactor |
STRINGi | 9606.ENSP00000244043 |
Chemistry databases
BindingDBi | Q16647 |
ChEMBLi | CHEMBL4428 |
DrugBanki | DB08675, (5Z)-7-{(1R,4S,5R,6R)-6-[(1E)-1-Octen-1-yl]-2,3-diazabicyclo[2.2.1]hept-2-en-5-yl}-5-heptenoic acid DB01240, Epoprostenol DB00812, Phenylbutazone |
DrugCentrali | Q16647 |
GuidetoPHARMACOLOGYi | 1356 |
SwissLipidsi | SLP:000001097 |
PTM databases
CarbonylDBi | Q16647 |
iPTMneti | Q16647 |
PhosphoSitePlusi | Q16647 |
Genetic variation databases
BioMutai | PTGIS |
DMDMi | 2493373 |
Proteomic databases
EPDi | Q16647 |
jPOSTi | Q16647 |
MassIVEi | Q16647 |
MaxQBi | Q16647 |
PaxDbi | Q16647 |
PeptideAtlasi | Q16647 |
PRIDEi | Q16647 |
ProteomicsDBi | 60999 |
Protocols and materials databases
Antibodypediai | 2399, 239 antibodies from 33 providers |
DNASUi | 5740 |
Genome annotation databases
Ensembli | ENST00000244043.5; ENSP00000244043.3; ENSG00000124212.6 |
GeneIDi | 5740 |
KEGGi | hsa:5740 |
MANE-Selecti | ENST00000244043.5; ENSP00000244043.3; NM_000961.4; NP_000952.1 |
UCSCi | uc002xut.4, human |
Organism-specific databases
CTDi | 5740 |
DisGeNETi | 5740 |
GeneCardsi | PTGIS |
HGNCi | HGNC:9603, PTGIS |
HPAi | ENSG00000124212, Tissue enhanced (endometrium, fallopian tube, urinary bladder) |
MalaCardsi | PTGIS |
MIMi | 145500, phenotype 601699, gene |
neXtProti | NX_Q16647 |
OpenTargetsi | ENSG00000124212 |
Orphaneti | 243761, NON RARE IN EUROPE: Essential hypertension |
PharmGKBi | PA292 |
VEuPathDBi | HostDB:ENSG00000124212 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00940000153709 |
HOGENOMi | CLU_018012_1_3_1 |
InParanoidi | Q16647 |
OMAi | EPQKYKY |
OrthoDBi | 454773at2759 |
PhylomeDBi | Q16647 |
TreeFami | TF105090 |
Enzyme and pathway databases
BRENDAi | 5.3.99.4, 2681 |
PathwayCommonsi | Q16647 |
Reactomei | R-HSA-193368, Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol R-HSA-193775, Synthesis of bile acids and bile salts via 24-hydroxycholesterol R-HSA-193807, Synthesis of bile acids and bile salts via 27-hydroxycholesterol R-HSA-197264, Nicotinamide salvaging R-HSA-211979, Eicosanoids R-HSA-211994, Sterols are 12-hydroxylated by CYP8B1 R-HSA-2162123, Synthesis of Prostaglandins (PG) and Thromboxanes (TX) |
SABIO-RKi | Q16647 |
SignaLinki | Q16647 |
Miscellaneous databases
BioGRID-ORCSi | 5740, 13 hits in 1077 CRISPR screens |
ChiTaRSi | PTGIS, human |
EvolutionaryTracei | Q16647 |
GeneWikii | Prostacyclin_synthase |
GenomeRNAii | 5740 |
Pharosi | Q16647, Tchem |
PROi | PR:Q16647 |
RNActi | Q16647, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000124212, Expressed in parietal pleura and 212 other tissues |
Genevisiblei | Q16647, HS |
Family and domain databases
DisProti | DP02578 |
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR024204, Cyt_P450_CYP7A1-type IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf IPR027286, PTGIS |
PANTHERi | PTHR24306:SF4, PTHR24306:SF4, 1 hit |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PIRSFi | PIRSF000047, Cytochrome_CYPVIIA1, 1 hit PIRSF500628, PTGIS, 1 hit |
PRINTSi | PR00465, EP450IV |
SUPFAMi | SSF48264, SSF48264, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | PTGIS_HUMAN | |
Accessioni | Q16647Primary (citable) accession number: Q16647 Secondary accession number(s): Q3MII8 Q9HAX4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 196 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families