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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi441 – 4411Iron (heme axial ligand)

GO - Molecular functioni

GO - Biological processi

  • apoptotic signaling pathway Source: UniProtKB
  • arachidonic acid metabolic process Source: Reactome
  • 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 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
  • small molecule metabolic process Source: Reactome
  • vitamin metabolic process Source: Reactome
  • water-soluble vitamin metabolic process Source: Reactome
  • xenobiotic metabolic process Source: Reactome
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.
BRENDAi5.3.99.4. 2681.
ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
REACT_11048. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
REACT_11053. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
REACT_11213. Nicotinamide salvaging.
REACT_13438. Sterols are 12-hydroxylated by CYP8B1.
REACT_13645. Eicosanoids.
REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

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
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:9603. PTGIS.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei1 – 2020HelicalSequence AnalysisAdd
BLAST

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

MIMi145500. phenotype.
PharmGKBiPA292.

Chemistry

DrugBankiDB01240. Epoprostenol.
DB00812. Phenylbutazone.

Polymorphism and mutation databases

BioMutaiPTGIS.
DMDMi2493373.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 500500Prostacyclin synthasePRO_0000051910Add
BLAST

Proteomic databases

MaxQBiQ16647.
PaxDbiQ16647.
PRIDEiQ16647.

PTM databases

PhosphoSiteiQ16647.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ16647.
CleanExiHS_PTGIS.
GenevisibleiQ16647. HS.

Organism-specific databases

HPAiCAB009517.
HPA014193.

Interactioni

Protein-protein interaction databases

BioGridi111712. 4 interactions.
STRINGi9606.ENSP00000244043.

Structurei

Secondary structure

1
500
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni38 – 403Combined sources
Helixi43 – 486Combined sources
Helixi50 – 6112Combined sources
Beta strandi63 – 697Combined sources
Beta strandi72 – 776Combined sources
Helixi80 – 823Combined sources
Helixi83 – 875Combined sources
Turni91 – 933Combined sources
Beta strandi94 – 963Combined sources
Helixi98 – 1069Combined sources
Helixi117 – 1259Combined sources
Helixi130 – 15526Combined sources
Beta strandi160 – 1634Combined sources
Helixi164 – 18118Combined sources
Helixi190 – 21930Combined sources
Helixi224 – 24017Combined sources
Helixi243 – 2464Combined sources
Helixi254 – 26512Combined sources
Helixi270 – 28516Combined sources
Helixi288 – 30013Combined sources
Helixi303 – 31816Combined sources
Helixi333 – 3364Combined sources
Helixi339 – 35214Combined sources
Beta strandi357 – 3615Combined sources
Beta strandi365 – 3684Combined sources
Beta strandi374 – 3774Combined sources
Beta strandi382 – 3854Combined sources
Helixi388 – 3925Combined sources
Turni395 – 3973Combined sources
Beta strandi398 – 4003Combined sources
Turni406 – 4094Combined sources
Beta strandi414 – 4163Combined sources
Helixi444 – 46017Combined sources
Beta strandi462 – 4687Combined sources
Helixi478 – 4803Combined sources
Beta strandi482 – 4854Combined sources
Beta strandi488 – 4903Combined sources
Beta strandi493 – 4986Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2IAGX-ray2.15A/B23-500[»]
3B6HX-ray1.62A/B18-500[»]
ProteinModelPortaliQ16647.
SMRiQ16647. Positions 23-500.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16647.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00550000074551.
HOVERGENiHBG051100.
InParanoidiQ16647.
KOiK01831.
OMAiMCSVKSR.
OrthoDBiEOG7J9VP6.
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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti38 – 381P → L in allele CYP8A1*2. 1 Publication
VAR_010915
Natural varianti118 – 1181S → R in allele CYP8A1*3. 1 Publication
Corresponds to variant rs5622 [ dbSNP | Ensembl ].
VAR_010916
Natural varianti154 – 1541E → A.
Corresponds to variant rs5623 [ dbSNP | Ensembl ].
VAR_014634
Natural varianti171 – 1711F → L.
Corresponds to variant rs5624 [ dbSNP | Ensembl ].
VAR_014635
Natural varianti236 – 2361R → C.
Corresponds to variant rs5626 [ dbSNP | Ensembl ].
VAR_014636
Natural varianti379 – 3791R → S in allele CYP8A1*4. 1 Publication
Corresponds to variant rs56195291 [ dbSNP | Ensembl ].
VAR_010917
Natural varianti447 – 4471A → T in allele CYP8A1*5; results in a significantly decreased enzyme activity. 1 Publication
VAR_073186
Natural varianti500 – 5001P → S.
Corresponds to variant rs5584 [ dbSNP | Ensembl ].
VAR_014637

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.3. 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
EntryMethodResolution (Å)ChainPositionsPDBsum
2IAGX-ray2.15A/B23-500[»]
3B6HX-ray1.62A/B18-500[»]
ProteinModelPortaliQ16647.
SMRiQ16647. Positions 23-500.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111712. 4 interactions.
STRINGi9606.ENSP00000244043.

Chemistry

BindingDBiQ16647.
ChEMBLiCHEMBL4428.
DrugBankiDB01240. Epoprostenol.
DB00812. Phenylbutazone.

PTM databases

PhosphoSiteiQ16647.

Polymorphism and mutation databases

BioMutaiPTGIS.
DMDMi2493373.

Proteomic databases

MaxQBiQ16647.
PaxDbiQ16647.
PRIDEiQ16647.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000244043; ENSP00000244043; ENSG00000124212.
GeneIDi5740.
KEGGihsa:5740.
UCSCiuc002xut.3. human.

Organism-specific databases

CTDi5740.
GeneCardsiGC20M048120.
HGNCiHGNC:9603. PTGIS.
HPAiCAB009517.
HPA014193.
MIMi145500. phenotype.
601699. gene.
neXtProtiNX_Q16647.
PharmGKBiPA292.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00550000074551.
HOVERGENiHBG051100.
InParanoidiQ16647.
KOiK01831.
OMAiMCSVKSR.
OrthoDBiEOG7J9VP6.
PhylomeDBiQ16647.
TreeFamiTF105090.

Enzyme and pathway databases

BioCyciMetaCyc:HS04738-MONOMER.
BRENDAi5.3.99.4. 2681.
ReactomeiREACT_11041. Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
REACT_11048. Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
REACT_11053. Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
REACT_11213. Nicotinamide salvaging.
REACT_13438. Sterols are 12-hydroxylated by CYP8B1.
REACT_13645. Eicosanoids.
REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

Miscellaneous databases

EvolutionaryTraceiQ16647.
GeneWikiiProstacyclin_synthase.
GenomeRNAii5740.
NextBioi22344.
PROiQ16647.
SOURCEiSearch...

Gene expression databases

BgeeiQ16647.
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...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Aorta.
  2. "Characterization of new mutations in the coding sequence and 5'-untranslated region of the human prostacyclin synthase gene (CYP8A1)."
    Chevalier D., Cauffiez C., Bernard C., Lo-Guidice J.-M., Allorge D., Fazio F., Ferrari N., Libersa C., Lhermitte M., D'Halluin J.C., Broly F.
    Hum. Genet. 108:148-155(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS LEU-38; ARG-118 AND SER-379.
  3. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  5. "Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension."
    Nakayama T., Soma M., Watanabe Y., Hasimu B., Sato M., Aoi N., Kosuge K., Kanmatsuse K., Kokubun S., Marrow J.D., Oates J.A.
    Biochem. Biophys. Res. Commun. 297:1135-1139(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN EHT.
  6. "Analysis of genetic polymorphism and biochemical characterization of a functionally decreased variant in prostacyclin synthase gene (CYP8A1) in humans."
    Cho S.A., Rohn-Glowacki K.J., Jarrar Y.B., Yi M., Kim W.Y., Shin J.G., Lee S.J.
    Arch. Biochem. Biophys. 569C:10-18(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOPHYSICOCHEMICAL PROPERTIES, VARIANT THR-447, CHARACTERIZATION OF VARIANT THR-447, CATALYTIC ACTIVITY.
  7. "Crystal structure of the human prostacyclin synthase."
    Chiang C.W., Yeh H.C., Wang L.H., Chan N.L.
    J. Mol. Biol. 364:266-274(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 23-500 IN COMPLEX WITH HEME, COFACTOR.

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: July 22, 2015
This is version 155 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

External Data

Dasty 3

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 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.