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Q16647

- PTGIS_HUMAN

UniProt

Q16647 - PTGIS_HUMAN

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Protein

Prostacyclin synthase

Gene

PTGIS

Organism
Homo sapiens (Human)
Status
Reviewed - 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.

Cofactori

Heme group.1 Publication

Sites

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

GO - Molecular functioni

  1. heme binding Source: UniProtKB
  2. iron ion binding Source: InterPro
  3. monooxygenase activity Source: InterPro
  4. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen Source: InterPro
  5. prostaglandin-I synthase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic signaling pathway Source: UniProtKB
  2. arachidonic acid metabolic process Source: Reactome
  3. cellular response to hypoxia Source: UniProtKB
  4. cellular response to interleukin-1 Source: UniProtKB
  5. cellular response to interleukin-6 Source: UniProtKB
  6. cyclooxygenase pathway Source: Reactome
  7. icosanoid metabolic process Source: Reactome
  8. negative regulation of inflammatory response Source: UniProtKB
  9. negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  10. negative regulation of nitric oxide biosynthetic process Source: UniProtKB
  11. positive regulation of angiogenesis Source: UniProtKB
  12. positive regulation of execution phase of apoptosis Source: UniProtKB
  13. positive regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
  14. prostaglandin biosynthetic process Source: UniProtKB
  15. small molecule metabolic process Source: Reactome
  16. 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.
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_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:5.3.99.4)
Alternative name(s):
Prostaglandin I2 synthase
Gene namesi
Name:PTGIS
Synonyms:CYP8, CYP8A1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:9603. PTGIS.

Subcellular locationi

GO - Cellular componenti

  1. caveola Source: UniProtKB
  2. endoplasmic reticulum Source: UniProtKB
  3. endoplasmic reticulum membrane Source: Reactome
  4. extracellular space Source: UniProtKB
  5. integral component of membrane Source: UniProtKB-KW
  6. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA292.

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.
ExpressionAtlasiQ16647. baseline and differential.
GenevestigatoriQ16647.

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 – 403
Helixi43 – 486
Helixi50 – 6112
Beta strandi63 – 697
Beta strandi72 – 776
Helixi80 – 823
Helixi83 – 875
Turni91 – 933
Beta strandi94 – 963
Helixi98 – 1069
Helixi117 – 1259
Helixi130 – 15526
Beta strandi160 – 1634
Helixi164 – 18118
Helixi190 – 21930
Helixi224 – 24017
Helixi243 – 2464
Helixi254 – 26512
Helixi270 – 28516
Helixi288 – 30013
Helixi303 – 31816
Helixi333 – 3364
Helixi339 – 35214
Beta strandi357 – 3615
Beta strandi365 – 3684
Beta strandi374 – 3774
Beta strandi382 – 3854
Helixi388 – 3925
Turni395 – 3973
Beta strandi398 – 4003
Turni406 – 4094
Beta strandi414 – 4163
Helixi444 – 46017
Beta strandi462 – 4687
Helixi478 – 4803
Beta strandi482 – 4854
Beta strandi488 – 4903
Beta strandi493 – 4986

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Transmembrane

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

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00550000074551.
HOVERGENiHBG051100.
InParanoidiQ16647.
KOiK01831.
OMAiSQMTTLP.
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 varianti500 – 5001P → S.
Corresponds to variant rs5584 [ dbSNP | Ensembl ].
VAR_014637

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi2493373.

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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS13419.1.
PIRi JC2231.
RefSeqi NP_000952.1. NM_000961.3.
UniGenei Hs.302085.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali Q16647.
SMRi Q16647. Positions 23-500.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 111712. 4 interactions.
STRINGi 9606.ENSP00000244043.

Chemistry

BindingDBi Q16647.
ChEMBLi CHEMBL4428.
DrugBanki DB01240. Epoprostenol.
DB00812. Phenylbutazone.

PTM databases

PhosphoSitei Q16647.

Polymorphism databases

DMDMi 2493373.

Proteomic databases

MaxQBi Q16647.
PaxDbi Q16647.
PRIDEi Q16647.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000244043 ; ENSP00000244043 ; ENSG00000124212 .
GeneIDi 5740.
KEGGi hsa:5740.
UCSCi uc002xut.3. human.

Organism-specific databases

CTDi 5740.
GeneCardsi GC20M048120.
HGNCi HGNC:9603. PTGIS.
HPAi CAB009517.
HPA014193.
MIMi 601699. gene.
neXtProti NX_Q16647.
PharmGKBi PA292.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2124.
GeneTreei ENSGT00550000074551.
HOVERGENi HBG051100.
InParanoidi Q16647.
KOi K01831.
OMAi SQMTTLP.
OrthoDBi EOG7J9VP6.
PhylomeDBi Q16647.
TreeFami TF105090.

Enzyme and pathway databases

BioCyci MetaCyc:HS04738-MONOMER.
Reactomei REACT_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_13438. Sterols are 12-hydroxylated by CYP8B1.
REACT_13645. Eicosanoids.
REACT_150149. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).

Miscellaneous databases

EvolutionaryTracei Q16647.
GeneWikii Prostacyclin_synthase.
GenomeRNAii 5740.
NextBioi 22344.
PROi Q16647.
SOURCEi Search...

Gene expression databases

Bgeei Q16647.
CleanExi HS_PTGIS.
ExpressionAtlasi Q16647. baseline and differential.
Genevestigatori Q16647.

Family and domain databases

Gene3Di 1.10.630.10. 1 hit.
InterProi IPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
IPR027286. PTGIS.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PIRSFi PIRSF000047. Cytochrome_CYPVIIA1. 1 hit.
PIRSF500628. PTGIS. 1 hit.
PRINTSi PR00465. EP450IV.
SUPFAMi SSF48264. SSF48264. 1 hit.
ProtoNeti Search...

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. "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: October 29, 2014
This is version 147 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