PTGIS_RAT
ID PTGIS_RAT Reviewed; 501 AA.
AC Q62969;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Prostacyclin synthase;
DE EC=5.3.99.4 {ECO:0000250|UniProtKB:Q16647};
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Geraci M.W., Gao B., Shepherd D., Moore M., Vernon J., Miller Y.E.,
RA Voelkel N.F.;
RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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. Additionally, displays dehydratase activity,
CC toward hydroperoxyeicosatetraenoates (HPETEs), especially toward (15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE).
CC {ECO:0000250|UniProtKB:Q16647}.
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:0000250|UniProtKB:Q16647};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23581;
CC Evidence={ECO:0000250|UniProtKB:Q16647};
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:0000250|UniProtKB:Q29626}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; U53855; AAB02322.1; -; mRNA.
DR EMBL; BC061814; AAH61814.1; -; mRNA.
DR RefSeq; NP_113745.1; NM_031557.2.
DR AlphaFoldDB; Q62969; -.
DR SMR; Q62969; -.
DR BioGRID; 247559; 1.
DR IntAct; Q62969; 1.
DR STRING; 10116.ENSRNOP00000010891; -.
DR PhosphoSitePlus; Q62969; -.
DR PaxDb; Q62969; -.
DR PRIDE; Q62969; -.
DR Ensembl; ENSRNOT00000115486; ENSRNOP00000087709; ENSRNOG00000008245.
DR GeneID; 25527; -.
DR KEGG; rno:25527; -.
DR UCSC; RGD:3438; rat.
DR CTD; 5740; -.
DR RGD; 3438; Ptgis.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153709; -.
DR InParanoid; Q62969; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; Q62969; -.
DR BRENDA; 5.3.99.4; 5301.
DR Reactome; R-RNO-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-RNO-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-RNO-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-RNO-197264; Nicotinamide salvaging.
DR Reactome; R-RNO-211979; Eicosanoids.
DR Reactome; R-RNO-211994; Sterols are 12-hydroxylated by CYP8B1.
DR Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR PRO; PR:Q62969; -.
DR Proteomes; UP000002494; Chromosome 3.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
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:0046697; P:decidualization; ISO:RGD.
DR GO; GO:0007566; P:embryo implantation; ISO:RGD.
DR GO; GO:0006690; P:icosanoid metabolic process; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IMP:RGD.
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; 2.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PIRSF; PIRSF500628; PTGIS; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 2: Evidence at transcript level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Heme; Iron; Isomerase; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Membrane; Metal-binding; Prostaglandin biosynthesis;
KW Prostaglandin metabolism; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..501
FT /note="Prostacyclin synthase"
FT /id="PRO_0000051912"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 107
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 113
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 288
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 359..360
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 383
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:F1RE08"
FT BINDING 442
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"
SQ SEQUENCE 501 AA; 57128 MW; D2D85ADF3C464863 CRC64;
MSWAALLGLL AVLLLLLLLL SRRRARRPGE PPLDLGSIPW LGHALEFGKD AASFLTRMKE
KHGDIFTVLV GGRYVTVLLD PHSYDTVVWD LRTRLDFHPY AIFLMERIFD LQLPNFNPSE
EKARMKPTLM HKDLQALTEA MYTNLRTVLL GDSTEGGSGW QEKGLLEFSY SSLLSAGYLT
LYGVEASPRT HESQALDRDH SADVFRTFRQ LDLMLPKLAR GSLSVGDKDH ACSVKSRLWK
LLSPAGLASR ADRSSWLESY LRHLEEMGVS EDMQARALVL QLWATQGNMG PTAFWLLLFL
LKNPEALDAV HAELKRIVWQ AEKPVLQMTA LPQKILDSMP VLDSVLNETL RLTAAPFITR
EVMADLALPM ADRREFSLRR GDRLLLFPFL SPQKDPEIYT EPEVFKYNRF LNPDGSEKKD
FYKDGKRLKN YNMPWGAGHN QCLGKSYAIN SIKQFVVLLL THFDLELVSE DTEVPEFDLS
RYGFGLMQPE EDVPIRYRTR L
