ID   PTGIS_MOUSE             Reviewed;         501 AA.
AC   O35074;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   24-JAN-2024, entry version 171.
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   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Peritoneal macrophage;
RX   PubMed=9202154; DOI=10.1016/s0014-5793(97)00516-4;
RA   Kuwamoto S., Inoue H., Tone Y., Izumi Y., Tanabe T.;
RT   "Inverse gene expression of prostacyclin and thromboxane synthases in
RT   resident and activated peritoneal macrophages.";
RL   FEBS Lett. 409:242-246(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Limb;
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).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Heart, Kidney, Lung, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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         (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + 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; AB001607; BAA21717.1; -; mRNA.
DR   EMBL; AK076585; BAC36403.1; -; mRNA.
DR   EMBL; BC062151; AAH62151.1; -; mRNA.
DR   CCDS; CCDS17097.1; -.
DR   RefSeq; NP_032994.1; NM_008968.3.
DR   AlphaFoldDB; O35074; -.
DR   SMR; O35074; -.
DR   BioGRID; 202461; 1.
DR   STRING; 10090.ENSMUSP00000018113; -.
DR   iPTMnet; O35074; -.
DR   PhosphoSitePlus; O35074; -.
DR   SwissPalm; O35074; -.
DR   MaxQB; O35074; -.
DR   PaxDb; 10090-ENSMUSP00000018113; -.
DR   PeptideAtlas; O35074; -.
DR   ProteomicsDB; 301870; -.
DR   Pumba; O35074; -.
DR   Antibodypedia; 2399; 279 antibodies from 33 providers.
DR   DNASU; 19223; -.
DR   Ensembl; ENSMUST00000018113.8; ENSMUSP00000018113.8; ENSMUSG00000017969.14.
DR   GeneID; 19223; -.
DR   KEGG; mmu:19223; -.
DR   UCSC; uc008nzl.1; mouse.
DR   AGR; MGI:1097156; -.
DR   CTD; 5740; -.
DR   MGI; MGI:1097156; Ptgis.
DR   VEuPathDB; HostDB:ENSMUSG00000017969; -.
DR   eggNOG; KOG0684; Eukaryota.
DR   GeneTree; ENSGT00940000153709; -.
DR   HOGENOM; CLU_018012_1_3_1; -.
DR   InParanoid; O35074; -.
DR   OMA; KFITRMK; -.
DR   OrthoDB; 1537669at2759; -.
DR   TreeFam; TF105090; -.
DR   Reactome; R-MMU-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR   Reactome; R-MMU-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR   Reactome; R-MMU-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR   Reactome; R-MMU-197264; Nicotinamide salvaging.
DR   Reactome; R-MMU-211979; Eicosanoids.
DR   Reactome; R-MMU-211994; Sterols are 12-hydroxylated by CYP8B1.
DR   Reactome; R-MMU-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR   BioGRID-ORCS; 19223; 3 hits in 82 CRISPR screens.
DR   ChiTaRS; Ptgis; mouse.
DR   PRO; PR:O35074; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; O35074; Protein.
DR   Bgee; ENSMUSG00000017969; Expressed in aorta tunica media and 209 other cell types or tissues.
DR   ExpressionAtlas; O35074; baseline and differential.
DR   GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
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; ISS:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
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:0097190; P:apoptotic signaling pathway; ISO:MGI.
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; IDA:MGI.
DR   GO; GO:0007566; P:embryo implantation; IDA:MGI.
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   GO; GO:0001666; P:response to hypoxia; ISO:MGI.
DR   CDD; cd20634; PGIS_CYP8A1; 1.
DR   Gene3D; 1.10.630.10; Cytochrome P450; 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; -; 1.
DR   PANTHER; PTHR24306:SF4; PROSTACYCLIN SYNTHASE; 1.
DR   Pfam; PF00067; p450; 1.
DR   PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR   PIRSF; PIRSF500628; PTGIS; 1.
DR   PRINTS; PR00465; EP450IV.
DR   PRINTS; PR00385; P450.
DR   SUPFAM; SSF48264; Cytochrome P450; 1.
DR   Genevisible; O35074; MM.
PE   1: Evidence at protein 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_0000051911"
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;  57047 MW;  F018F85D3A1B0EBB CRC64;
     MSWAALLGLL AVLLLLLLLL SRRRARRPGE PPLDLGSIPW LGHALEFGRD AASFLTRMKE
     KHGDIFTVLV GGRYVTVLLD PHSYDTVVWE LRTRLDFHPY AIFLMERIFD LQLPNFNPSE
     EKARMKPTLM HRDLQALTEA MYTNLRTVLL GDSTEAGSGW QETGLLEFSY NALLSAGYLT
     LYGVEASPRT HESQAQDRVH SADVFHTFRQ LDLLLPKLAR GSLSAGDKDH ACSVKNRLWK
     LLSPARLASR ADRSSWLESY LRHLEEMGVS EEMQARALVL QLWATQGNMG PTAFWLLLFL
     LKNPEALAAV RAELKHTVWQ AEQPVSQMTT LPQKILDSMP VLDSVLNETL RLTAAPFITR
     EVMADLALPM ADGREFSLRR GDRLLLFPFL SPQKDPEIYT EPEVFKYNRF LNPDGSEKKD
     FYKDGKRLKN YNMPWGAGHN QCLGKSYAIN SIKQFVVLLL THFDLELGSE DTEVPEFDLS
     RYGFGLMQPE EDVPIRYRAR L
//