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Protein

Prostacyclin synthase

Gene

PTGIS

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

Functioni

Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).2 Publications

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.2 Publications

Cofactori

heme2 Publications

Kineticsi

  1. KM=9.55 µM for 6-keto-PGF1alpha1 Publication
  2. KM=13 µM for prostaglandin H2 (at 23 degrees Celsius)1 Publication
  1. Vmax=534 mmol/min/pg enzyme1 Publication
  2. Vmax=980 mol/min/mol enzyme1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei106SubstrateBy similarity1
Binding sitei112Substrate; via amide nitrogenBy similarity1
Binding sitei287SubstrateBy similarity1
Binding sitei382SubstrateBy similarity1
Metal bindingi441Iron (heme axial ligand)Combined sources2 Publications1

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
  • 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 functionIsomerase
Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc: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:5.3.99.42 Publications)
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

EuPathDBiHostDB:ENSG00000124212.5
HGNCiHGNC:9603 PTGIS
MIMi601699 gene
neXtProtiNX_Q16647

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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
ProteomicsDBi60999

PTM databases

CarbonylDBiQ16647
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
HPA052244

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

ProteinModelPortaliQ16647
SMRiQ16647
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16647

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni358 – 359Substrate bindingBy similarity2

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0684 Eukaryota
COG2124 LUCA
GeneTreeiENSGT00550000074551
HOVERGENiHBG051100
InParanoidiQ16647
KOiK01831
OMAiVFHTFRQ
OrthoDBiEOG091G0767
PhylomeDBiQ16647
TreeFamiTF105090

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128 Cyt_P450
IPR024204 Cyt_P450_CYP7A1-type
IPR002403 Cyt_P450_E_grp-IV
IPR036396 Cyt_P450_sf
IPR027286 PTGIS
PANTHERiPTHR24306:SF4 PTHR24306:SF4, 1 hit
PfamiView protein in Pfam
PF00067 p450, 1 hit
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 dbSNP:rs5622Ensembl.1
Natural variantiVAR_014634154E → A. Corresponds to variant dbSNP:rs5623Ensembl.1
Natural variantiVAR_014635171F → L. Corresponds to variant dbSNP:rs5624Ensembl.1
Natural variantiVAR_014636236R → C. Corresponds to variant dbSNP:rs5626Ensembl.1
Natural variantiVAR_010917379R → S in allele CYP8A1*4. 1 PublicationCorresponds to variant dbSNP:rs56195291Ensembl.1
Natural variantiVAR_073186447A → T in allele CYP8A1*5; results in a significantly decreased enzyme activity. 1 PublicationCorresponds to variant dbSNP:rs146531327Ensembl.1
Natural variantiVAR_014637500P → 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
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

Similar proteinsi

Entry informationi

Entry nameiPTGIS_HUMAN
AccessioniPrimary (citable) accession number: Q16647
Secondary accession number(s): Q3MII8
, Q9HAX2, Q9HAX3, Q9HAX4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: June 20, 2018
This is version 174 of the entry and version 1 of the sequence. See 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

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