PTGIS_BOVIN
ID PTGIS_BOVIN Reviewed; 500 AA.
AC Q29626; Q0P5G0; Q28841;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Prostacyclin synthase {ECO:0000303|PubMed:8051072};
DE EC=5.3.99.4 {ECO:0000269|PubMed:8051072, ECO:0000269|PubMed:8280118};
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase;
DE EC=4.2.1.152 {ECO:0000250|UniProtKB:Q16647};
DE AltName: Full=Prostaglandin I2 synthase;
GN Name=PTGIS; Synonyms=CYP8;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, CATALYTIC
RP ACTIVITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Aorta;
RX PubMed=8051072; DOI=10.1016/s0021-9258(17)32104-x;
RA Hara S., Miyata A., Yokoyama C., Inoue H., Brugger R., Lottspeich F.,
RA Ullrich V., Tanabe T.;
RT "Isolation and molecular cloning of prostacyclin synthase from bovine
RT endothelial cells.";
RL J. Biol. Chem. 269:19897-19903(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Aorta;
RX PubMed=8074709; DOI=10.1006/bbrc.1994.2148;
RA Pereira B., Wu K.K., Wang L.H.;
RT "Molecular cloning and characterization of bovine prostacyclin synthase.";
RL Biochem. Biophys. Res. Commun. 203:59-66(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal cerebellum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 9-30, PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Aorta;
RX PubMed=8280118; DOI=10.1006/bbrc.1993.2583;
RA Pereira B., Wu K.K., Wang L.H.;
RT "Bovine prostacyclin synthase: purification and isolation of partial
RT cDNA.";
RL Biochem. Biophys. Res. Commun. 197:1041-1048(1993).
CC -!- FUNCTION: Catalyzes the biosynthesis and metabolism of eicosanoids.
CC Catalyzes the isomerization of prostaglandin H2 to prostacyclin (=
CC prostaglandin I2), a potent mediator of vasodilation and inhibitor of
CC platelet aggregation (PubMed:8051072, PubMed:8280118). Additionally,
CC displays dehydratase activity, toward hydroperoxyeicosatetraenoates
CC (HPETEs), especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-
CC eicosatetraenoate (15(S)-HPETE) (By similarity).
CC {ECO:0000250|UniProtKB:Q16647, ECO:0000269|PubMed:8051072,
CC ECO:0000269|PubMed:8280118}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = prostaglandin I2; Xref=Rhea:RHEA:23580,
CC ChEBI:CHEBI:57403, ChEBI:CHEBI:57405; EC=5.3.99.4;
CC Evidence={ECO:0000269|PubMed:8051072, ECO:0000269|PubMed:8280118};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23581;
CC Evidence={ECO:0000305|PubMed:8051072, ECO:0000305|PubMed:8280118};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a hydroperoxyeicosatetraenoate = an oxoeicosatetraenoate +
CC H2O; Xref=Rhea:RHEA:55556, ChEBI:CHEBI:15377, ChEBI:CHEBI:59720,
CC ChEBI:CHEBI:131859; EC=4.2.1.152;
CC Evidence={ECO:0000250|UniProtKB:Q16647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55557;
CC Evidence={ECO:0000250|UniProtKB:Q16647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:48636,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:57446;
CC Evidence={ECO:0000250|UniProtKB:Q16647};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + AH2 =
CC (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + A + H2O;
CC Xref=Rhea:RHEA:48856, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:57409, ChEBI:CHEBI:57446;
CC Evidence={ECO:0000250|UniProtKB:Q16647};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q16647};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:8051072, ECO:0000305|PubMed:8280118}; Single-pass
CC membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D30718; BAA06383.1; -; mRNA.
DR EMBL; L34208; AAA53674.1; -; mRNA.
DR EMBL; BC120087; AAI20088.1; -; mRNA.
DR EMBL; S67757; AAB29680.1; -; mRNA.
DR PIR; A53658; A53658.
DR RefSeq; NP_776869.1; NM_174444.1.
DR AlphaFoldDB; Q29626; -.
DR SMR; Q29626; -.
DR STRING; 9913.ENSBTAP00000023313; -.
DR PaxDb; Q29626; -.
DR Ensembl; ENSBTAT00000023313; ENSBTAP00000023313; ENSBTAG00000017537.
DR GeneID; 282021; -.
DR KEGG; bta:282021; -.
DR CTD; 5740; -.
DR VEuPathDB; HostDB:ENSBTAG00000017537; -.
DR VGNC; VGNC:33509; PTGIS.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153709; -.
DR HOGENOM; CLU_018012_1_3_1; -.
DR InParanoid; Q29626; -.
DR OrthoDB; 572303at2759; -.
DR TreeFam; TF105090; -.
DR Proteomes; UP000009136; Chromosome 13.
DR Bgee; ENSBTAG00000017537; Expressed in trachea and 103 other tissues.
DR ExpressionAtlas; Q29626; baseline and differential.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0106256; F:hydroperoxy icosatetraenoate dehydratase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:InterPro.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0008116; F:prostaglandin-I synthase activity; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISS:UniProtKB.
DR GO; GO:0071354; P:cellular response to interleukin-6; ISS:UniProtKB.
DR GO; GO:0006690; P:icosanoid metabolic process; ISS:UniProtKB.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISS:UniProtKB.
DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR024204; Cyt_P450_CYP7A1-type.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR InterPro; IPR027286; PTGIS.
DR PANTHER; PTHR24306:SF4; PTHR24306:SF4; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PIRSF; PIRSF500628; PTGIS; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Heme; Iron; Isomerase; Lipid biosynthesis;
KW Lipid metabolism; Lyase; Membrane; Metal-binding;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..500
FT /note="Prostacyclin synthase"
FT /id="PRO_0000051909"
FT TRANSMEM 1..20
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 106
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 287
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 358..359
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 382
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 441
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:Q16647"
FT CONFLICT 192
FT /note="S -> N (in Ref. 2; AAA53674)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="A -> P (in Ref. 2; AAA53674)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="N -> T (in Ref. 2; AAA53674)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 500 AA; 56629 MW; 3728EEFEAE852403 CRC64;
MSWAVVFGLL AALLLLLLLT RRRTRRPGEP PLDLGSIPWL GHALEFGKDA AGFLTRMKEK
HGDIFTVLVG GRHVTVLLDP HSYDAVVWEP RSRLDFHAYA VFLMERIFDV QLPHYNPGDE
KSKMKPTLLH KELQALTDAM YTNLRTVLLG DTVEAGSGWH EMGLLEFSYG FLLRAGYLTQ
YGVEAPPHTQ ESQAQDRVHS ADVFHTFRQL DLLLPKLARG SLSAGDKDRV GKVKGRLWKL
LSPTRLASRA HRSRWLESYL LHLEEMGVSE EMQARALVLQ LWATQGNMGP AAFWLLLFLL
KNPEALAAVR GELETVLLGA EQPISQMTTL PQKVLDSMPV LDSVLSESLR LTAAPFITRE
VVADLALPMA DGREFSLRRG DRLLLFPFLS PQKDPEIYTD PEVFKYNRFL NPDGSEKKDF
YKDGKRLKNY SLPWGAGHNQ CLGKGYAVNS IKQFVFLVLT QFDLELITPD VDIPEFDLSR
YGFGLMQPEH DVPVRYRIRP
