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Protein

Prostacyclin synthase

Gene

PTGIS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).

Catalytic activityi

(5Z,13E)-(15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E)-(15S)-6,9-alpha-epoxy-11-alpha,15-dihydroxyprosta-5,13-dienoate.1 Publication

Cofactori

heme1 Publication

Kineticsi

  1. KM=9.55 µM for 6-keto-PGF1alpha1 Publication
  1. Vmax=534 mmol/min/pg enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi441Iron (heme axial ligand)1

GO - Molecular functioni

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
  • decidualization Source: Ensembl
  • embryo implantation Source: Ensembl
  • icosanoid metabolic process 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
  • nicotinamide metabolic process Source: Reactome
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Isomerase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS04738-MONOMER.
ZFISH:HS04738-MONOMER.
BRENDAi5.3.99.4. 2681.
ReactomeiR-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).

Chemistry databases

SwissLipidsiSLP:000001097.

Names & Taxonomyi

Protein namesi
Recommended name:
Prostacyclin synthase (EC:5.3.99.41 Publication)
Alternative name(s):
Prostaglandin I2 synthase
Gene namesi
Name:PTGIS
Synonyms:CYP8, CYP8A1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:9603. PTGIS.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei1 – 20HelicalSequence analysisAdd BLAST20

GO - Cellular componenti

  • caveola Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: Reactome
  • extracellular space Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Essential hypertension (EHT)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition in which blood pressure is consistently higher than normal with no identifiable cause.
See also OMIM:145500

Organism-specific databases

DisGeNETi5740.
MalaCardsiPTGIS.
MIMi145500. phenotype.
OpenTargetsiENSG00000124212.
PharmGKBiPA292.

Chemistry databases

ChEMBLiCHEMBL4428.
DrugBankiDB01240. Epoprostenol.
DB00812. Phenylbutazone.
GuidetoPHARMACOLOGYi1356.

Polymorphism and mutation databases

BioMutaiPTGIS.
DMDMi2493373.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000519101 – 500Prostacyclin synthaseAdd BLAST500

Proteomic databases

EPDiQ16647.
MaxQBiQ16647.
PaxDbiQ16647.
PeptideAtlasiQ16647.
PRIDEiQ16647.

PTM databases

iPTMnetiQ16647.
PhosphoSitePlusiQ16647.

Expressioni

Tissue specificityi

Widely expressed; particularly abundant in ovary, heart, skeletal muscle, lung and prostate.

Gene expression databases

BgeeiENSG00000124212.
CleanExiHS_PTGIS.
GenevisibleiQ16647. HS.

Organism-specific databases

HPAiCAB009517.
HPA014193.

Interactioni

Protein-protein interaction databases

BioGridi111712. 4 interactors.
STRINGi9606.ENSP00000244043.

Chemistry databases

BindingDBiQ16647.

Structurei

Secondary structure

1500
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni38 – 40Combined sources3
Helixi43 – 48Combined sources6
Helixi50 – 61Combined sources12
Beta strandi63 – 69Combined sources7
Beta strandi72 – 77Combined sources6
Helixi80 – 82Combined sources3
Helixi83 – 87Combined sources5
Turni91 – 93Combined sources3
Beta strandi94 – 96Combined sources3
Helixi98 – 106Combined sources9
Helixi117 – 125Combined sources9
Helixi130 – 155Combined sources26
Beta strandi160 – 163Combined sources4
Helixi164 – 181Combined sources18
Helixi190 – 219Combined sources30
Helixi224 – 240Combined sources17
Helixi243 – 246Combined sources4
Helixi254 – 265Combined sources12
Helixi270 – 285Combined sources16
Helixi288 – 300Combined sources13
Helixi303 – 318Combined sources16
Helixi333 – 336Combined sources4
Helixi339 – 352Combined sources14
Beta strandi357 – 361Combined sources5
Beta strandi365 – 368Combined sources4
Beta strandi374 – 377Combined sources4
Beta strandi382 – 385Combined sources4
Helixi388 – 392Combined sources5
Turni395 – 397Combined sources3
Beta strandi398 – 400Combined sources3
Turni406 – 409Combined sources4
Beta strandi414 – 416Combined sources3
Helixi444 – 460Combined sources17
Beta strandi462 – 468Combined sources7
Helixi478 – 480Combined sources3
Beta strandi482 – 485Combined sources4
Beta strandi488 – 490Combined sources3
Beta strandi493 – 498Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IAGX-ray2.15A/B23-500[»]
3B6HX-ray1.62A/B18-500[»]
ProteinModelPortaliQ16647.
SMRiQ16647.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16647.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0684. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00550000074551.
HOVERGENiHBG051100.
InParanoidiQ16647.
KOiK01831.
OMAiPRTHESQ.
OrthoDBiEOG091G0767.
PhylomeDBiQ16647.
TreeFamiTF105090.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
IPR027286. PTGIS.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PIRSFiPIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PIRSF500628. PTGIS. 1 hit.
PRINTSiPR00465. EP450IV.
SUPFAMiSSF48264. SSF48264. 1 hit.

Sequencei

Sequence statusi: Complete.

Q16647-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:500
Mass (Da):57,104
Last modified:November 1, 1996 - v1
Checksum:i39595442BFC0B625
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01091538P → L in allele CYP8A1*2. 1 Publication1
Natural variantiVAR_010916118S → R in allele CYP8A1*3. 1 PublicationCorresponds to variant rs5622dbSNPEnsembl.1
Natural variantiVAR_014634154E → A.Corresponds to variant rs5623dbSNPEnsembl.1
Natural variantiVAR_014635171F → L.Corresponds to variant rs5624dbSNPEnsembl.1
Natural variantiVAR_014636236R → C.Corresponds to variant rs5626dbSNPEnsembl.1
Natural variantiVAR_010917379R → S in allele CYP8A1*4. 1 PublicationCorresponds to variant rs56195291dbSNPEnsembl.1
Natural variantiVAR_073186447A → T in allele CYP8A1*5; results in a significantly decreased enzyme activity. 1 PublicationCorresponds to variant rs146531327dbSNPEnsembl.1
Natural variantiVAR_014637500P → S.Corresponds to variant rs5584dbSNPEnsembl.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. Translation: CAC14162.1.
BC101809 mRNA. Translation: AAI01810.1.
BC101811 mRNA. Translation: AAI01812.1.
CCDSiCCDS13419.1.
PIRiJC2231.
RefSeqiNP_000952.1. NM_000961.3.
UniGeneiHs.302085.

Genome annotation databases

EnsembliENST00000244043; ENSP00000244043; ENSG00000124212.
GeneIDi5740.
KEGGihsa:5740.
UCSCiuc002xut.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Cytochrome P450 Allele Nomenclature Committee

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. Translation: CAC14162.1.
BC101809 mRNA. Translation: AAI01810.1.
BC101811 mRNA. Translation: AAI01812.1.
CCDSiCCDS13419.1.
PIRiJC2231.
RefSeqiNP_000952.1. NM_000961.3.
UniGeneiHs.302085.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IAGX-ray2.15A/B23-500[»]
3B6HX-ray1.62A/B18-500[»]
ProteinModelPortaliQ16647.
SMRiQ16647.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111712. 4 interactors.
STRINGi9606.ENSP00000244043.

Chemistry databases

BindingDBiQ16647.
ChEMBLiCHEMBL4428.
DrugBankiDB01240. Epoprostenol.
DB00812. Phenylbutazone.
GuidetoPHARMACOLOGYi1356.
SwissLipidsiSLP:000001097.

PTM databases

iPTMnetiQ16647.
PhosphoSitePlusiQ16647.

Polymorphism and mutation databases

BioMutaiPTGIS.
DMDMi2493373.

Proteomic databases

EPDiQ16647.
MaxQBiQ16647.
PaxDbiQ16647.
PeptideAtlasiQ16647.
PRIDEiQ16647.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000244043; ENSP00000244043; ENSG00000124212.
GeneIDi5740.
KEGGihsa:5740.
UCSCiuc002xut.4. human.

Organism-specific databases

CTDi5740.
DisGeNETi5740.
GeneCardsiPTGIS.
HGNCiHGNC:9603. PTGIS.
HPAiCAB009517.
HPA014193.
MalaCardsiPTGIS.
MIMi145500. phenotype.
601699. gene.
neXtProtiNX_Q16647.
OpenTargetsiENSG00000124212.
PharmGKBiPA292.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0684. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00550000074551.
HOVERGENiHBG051100.
InParanoidiQ16647.
KOiK01831.
OMAiPRTHESQ.
OrthoDBiEOG091G0767.
PhylomeDBiQ16647.
TreeFamiTF105090.

Enzyme and pathway databases

BioCyciMetaCyc:HS04738-MONOMER.
ZFISH:HS04738-MONOMER.
BRENDAi5.3.99.4. 2681.
ReactomeiR-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).

Miscellaneous databases

EvolutionaryTraceiQ16647.
GeneWikiiProstacyclin_synthase.
GenomeRNAii5740.
PROiQ16647.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124212.
CleanExiHS_PTGIS.
GenevisibleiQ16647. HS.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
IPR027286. PTGIS.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PIRSFiPIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PIRSF500628. PTGIS. 1 hit.
PRINTSiPR00465. EP450IV.
SUPFAMiSSF48264. SSF48264. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPTGIS_HUMAN
AccessioniPrimary (citable) accession number: Q16647
Secondary accession number(s): Q3MII8
, Q9HAX2, Q9HAX3, Q9HAX4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 165 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.