Q16647 (PTGIS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Prostacyclin synthase
EC=5.3.99.4

Alternative name(s):
Prostaglandin I2 synthase

Gene names

Name:	PTGIS
Synonyms:	CYP8, CYP8A1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	500 AA.
Sequence status	Complete.
Protein existence	Evidence 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 By similarity.
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 process	Fatty acid biosynthesis Lipid synthesis Prostaglandin biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding
Molecular function	Isomerase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	prostaglandin biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum lumen Traceable author statement. Source: Reactome endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme 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 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 500

500

Prostacyclin synthase

PRO_0000051910

Regions

Transmembrane

1 – 20

20

Helical; Potential

Sites

Metal binding

441

1

Iron (heme axial ligand) By similarity

Natural variations

Natural variant

38

1

P → L in allele CYP8A1*2. Ref.2

VAR_010915

Natural variant

118

1

S → R in allele CYP8A1*3. Ref.2
Corresponds to variant rs5622 [ dbSNP | Ensembl ].

VAR_010916

Natural variant

154

1

E → A.
Corresponds to variant rs5623 [ dbSNP | Ensembl ].

VAR_014634

Natural variant

171

1

F → L.
Corresponds to variant rs5624 [ dbSNP | Ensembl ].

VAR_014635

Natural variant

236

1

R → C.
Corresponds to variant rs5626 [ dbSNP | Ensembl ].

VAR_014636

Natural variant

379

1

R → S in allele CYP8A1*4. Ref.2
Corresponds to variant rs56195291 [ dbSNP | Ensembl ].

VAR_010917

Natural variant

500

1

P → S.
Corresponds to variant rs5584 [ dbSNP | Ensembl ].

VAR_014637

Secondary structure

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500

Helix Strand Turn

Details...

Turn

38 – 40

3

Helix

43 – 48

6

Helix

50 – 61

12

Beta strand

63 – 69

7

Beta strand

72 – 77

6

Helix

80 – 83

4

Helix

84 – 87

4

Turn

91 – 93

3

Beta strand

94 – 96

3

Helix

97 – 108

12

Helix

117 – 126

10

Helix

130 – 155

26

Beta strand

160 – 163

4

Helix

164 – 181

18

Helix

190 – 212

23

Helix

214 – 219

6

Helix

224 – 240

17

Helix

243 – 246

4

Helix

254 – 265

12

Helix

270 – 285

16

Helix

288 – 301

14

Helix

303 – 317

15

Helix

332 – 336

5

Helix

339 – 352

14

Beta strand

357 – 361

5

Beta strand

365 – 368

4

Beta strand

374 – 377

4

Beta strand

382 – 385

4

Helix

388 – 392

5

Turn

395 – 397

3

Beta strand

398 – 400

3

Turn

406 – 409

4

Beta strand

414 – 416

3

Helix

444 – 461

18

Beta strand

462 – 468

7

Helix

478 – 480

3

Beta strand

482 – 485

4

Beta strand

488 – 490

3

Beta strand

493 – 498

6

Sequences

	Sequence		Length	Mass (Da)
	Q16647 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 39595442BFC0B625	FASTA	500	57,104
	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

References

	« Hide 'large scale' referencesShow '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: 8185632] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Aorta.
[2]	"Characterization of new mutations in the coding sequence and 5'-untranslated region of the human prostacylcin 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: 11281454] [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: 11780052] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP8A1 alleles

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.

IPI

IPI00003411.

PIR

JC2231.

RefSeq

NP_000952.1. NM_000961.3.

UniGene

Hs.302085.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q16647.

SMR

Q16647. Positions 23-500.

ModBase

Search...

Protein-protein interaction databases

STRING

Q16647.

Polymorphism databases

DMDM

2493373.

Proteomic databases

PRIDE

Q16647.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000244043; ENSP00000244043; ENSG00000124212.

GeneID

5740.

KEGG

hsa:5740.

UCSC

uc002xut.1. human.

Organism-specific databases

CTD

5740.

GeneCards

GC20M048120.

H-InvDB

HIX0027668.

HGNC

HGNC:9603. PTGIS.

HPA

CAB009517.
HPA014193.

MIM

601699. gene.

neXtProt

NX_Q16647.

PharmGKB

PA292.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15337.

HOVERGEN

HBG051100.

InParanoid

Q16647.

OMA

QMTTLPQ.

OrthoDB

EOG43BMP2.

PhylomeDB

Q16647.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.
REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q16647.

Bgee

Q16647.

CleanEx

HS_PTGIS.

Genevestigator

Q16647.

GermOnline

ENSG00000124212. Homo sapiens.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR024204. Cyt_P450_CYP7A1-type.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

KO

K01831.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PIRSF

PIRSF000047. Cytochrome_CYPVIIA1. 1 hit.

PRINTS

PR00465. EP450IV.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. False negative.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00812. Phenylbutazone.

NextBio

22344.

SOURCE

Search...

Entry information

Entry name

PTGIS_HUMAN

Accession

Primary (citable) accession number: Q16647
Secondary accession number(s): Q3MII8 , Q9HAX2, Q9HAX3, Q9HAX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.