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Q16647 (PTGIS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Prostacyclin synthase

EC=5.3.99.4
Alternative name(s):
Prostaglandin I2 synthase
Gene names
Name:PTGIS
Synonyms:CYP8, CYP8A1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length500 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

(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.

Cofactor

Heme group. Ref.5

Subcellular location

Endoplasmic reticulum membrane; Single-pass membrane protein.

Tissue specificity

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

Sequence similarities

Belongs to the cytochrome P450 family.

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Prostaglandin biosynthesis
Prostaglandin metabolism
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   LigandHeme
Iron
Metal-binding
   Molecular functionIsomerase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic signaling pathway

Inferred from direct assay PubMed 11551955. Source: UniProtKB

arachidonic acid metabolic process

Traceable author statement. Source: Reactome

cellular response to hypoxia

Inferred from direct assay PubMed 21296955. Source: UniProtKB

cellular response to interleukin-1

Inferred from expression pattern Ref.1. Source: UniProtKB

cellular response to interleukin-6

Inferred from expression pattern Ref.1. Source: UniProtKB

cyclooxygenase pathway

Traceable author statement. Source: Reactome

icosanoid metabolic process

Traceable author statement. Source: Reactome

negative regulation of NF-kappaB transcription factor activity

Inferred from direct assay PubMed 20159982. Source: UniProtKB

negative regulation of inflammatory response

Inferred from direct assay PubMed 20159982. Source: UniProtKB

negative regulation of nitric oxide biosynthetic process

Inferred from direct assay PubMed 20159982. Source: UniProtKB

positive regulation of angiogenesis

Inferred from mutant phenotype PubMed 20122998. Source: UniProtKB

positive regulation of execution phase of apoptosis

Inferred from direct assay PubMed 11551955. Source: UniProtKB

positive regulation of peroxisome proliferator activated receptor signaling pathway

Inferred from direct assay PubMed 11551955. Source: UniProtKB

prostaglandin biosynthetic process

Inferred from direct assay PubMed 20122998PubMed 21296955. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcaveola

Inferred from direct assay PubMed 20122998. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay PubMed 21035466. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from direct assay PubMed 21035466. Source: UniProtKB

   Molecular_functionheme binding

Inferred from direct assay Ref.5. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

monooxygenase activity

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen

Inferred from electronic annotation. Source: InterPro

prostaglandin-I synthase activity

Inferred from direct assay PubMed 20122998PubMed 21296955. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 20122998. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 500500Prostacyclin synthase
PRO_0000051910

Regions

Transmembrane1 – 2020Helical; Potential

Sites

Metal binding4411Iron (heme axial ligand)

Natural variations

Natural variant381P → L in allele CYP8A1*2. Ref.2
VAR_010915
Natural variant1181S → R in allele CYP8A1*3. Ref.2
Corresponds to variant rs5622 [ dbSNP | Ensembl ].
VAR_010916
Natural variant1541E → A.
Corresponds to variant rs5623 [ dbSNP | Ensembl ].
VAR_014634
Natural variant1711F → L.
Corresponds to variant rs5624 [ dbSNP | Ensembl ].
VAR_014635
Natural variant2361R → C.
Corresponds to variant rs5626 [ dbSNP | Ensembl ].
VAR_014636
Natural variant3791R → S in allele CYP8A1*4. Ref.2
Corresponds to variant rs56195291 [ dbSNP | Ensembl ].
VAR_010917
Natural variant5001P → S.
Corresponds to variant rs5584 [ dbSNP | Ensembl ].
VAR_014637

Secondary structure

......................................................................... 500
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16647 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 39595442BFC0B625

FASTA50057,104
        10         20         30         40         50         60 
MAWAALLGLL AALLLLLLLS RRRTRRPGEP PLDLGSIPWL GYALDFGKDA ASFLTRMKEK 

        70         80         90        100        110        120 
HGDIFTILVG GRYVTVLLDP HSYDAVVWEP RTRLDFHAYA IFLMERIFDV QLPHYSPSDE 

       130        140        150        160        170        180 
KARMKLTLLH RELQALTEAM YTNLHAVLLG DATEAGSGWH EMGLLDFSYS FLLRAGYLTL 

       190        200        210        220        230        240 
YGIEALPRTH ESQAQDRVHS ADVFHTFRQL DRLLPKLARG SLSVGDKDHM CSVKSRLWKL 

       250        260        270        280        290        300 
LSPARLARRA HRSKWLESYL LHLEEMGVSE EMQARALVLQ LWATQGNMGP AAFWLLLFLL 

       310        320        330        340        350        360 
KNPEALAAVR GELESILWQA EQPVSQTTTL PQKVLDSTPV LDSVLSESLR LTAAPFITRE 

       370        380        390        400        410        420 
VVVDLAMPMA DGREFNLRRG DRLLLFPFLS PQRDPEIYTD PEVFKYNRFL NPDGSEKKDF 

       430        440        450        460        470        480 
YKDGKRLKNY NMPWGAGHNH CLGRSYAVNS IKQFVFLVLV HLDLELINAD VEIPEFDLSR 

       490        500 
YGFGLMQPEH DVPVRYRIRP 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of human prostacyclin synthase."
Miyata A., Hara S., Yokoyama C., Inoue H., Ullrich V., Tanabe T.
Biochem. Biophys. Res. Commun. 200:1728-1734(1994) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS13419.1.
PIRJC2231.
RefSeqNP_000952.1. NM_000961.3.
UniGeneHs.302085.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2IAGX-ray2.15A/B23-500[»]
3B6HX-ray1.62A/B18-500[»]
ProteinModelPortalQ16647.
SMRQ16647. Positions 23-500.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111712. 4 interactions.
STRING9606.ENSP00000244043.

Chemistry

BindingDBQ16647.
ChEMBLCHEMBL4428.
DrugBankDB00812. Phenylbutazone.

PTM databases

PhosphoSiteQ16647.

Polymorphism databases

DMDM2493373.

Proteomic databases

MaxQBQ16647.
PaxDbQ16647.
PRIDEQ16647.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000244043; ENSP00000244043; ENSG00000124212.
GeneID5740.
KEGGhsa:5740.
UCSCuc002xut.3. human.

Organism-specific databases

CTD5740.
GeneCardsGC20M048120.
HGNCHGNC:9603. PTGIS.
HPACAB009517.
HPA014193.
MIM601699. gene.
neXtProtNX_Q16647.
PharmGKBPA292.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOVERGENHBG051100.
InParanoidQ16647.
KOK01831.
OMASQMTTLP.
OrthoDBEOG7J9VP6.
PhylomeDBQ16647.
TreeFamTF105090.

Enzyme and pathway databases

BioCycMetaCyc:HS04738-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressQ16647.
BgeeQ16647.
CleanExHS_PTGIS.
GenevestigatorQ16647.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
IPR027286. PTGIS.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PIRSFPIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PIRSF500628. PTGIS. 1 hit.
PRINTSPR00465. EP450IV.
SUPFAMSSF48264. SSF48264. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ16647.
GeneWikiProstacyclin_synthase.
GenomeRNAi5740.
NextBio22344.
PROQ16647.
SOURCESearch...

Entry information

Entry namePTGIS_HUMAN
AccessionPrimary (citable) accession number: Q16647
Secondary accession number(s): Q3MII8 expand/collapse secondary AC list , Q9HAX2, Q9HAX3, Q9HAX4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM