ID PTGIS_HUMAN Reviewed; 500 AA. AC Q16647; Q3MII8; Q9HAX2; Q9HAX3; Q9HAX4; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 206. DE RecName: Full=Prostacyclin synthase; DE EC=5.3.99.4 {ECO:0000269|PubMed:15115769, ECO:0000269|PubMed:18032380, ECO:0000269|PubMed:25623425}; DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase {ECO:0000305}; DE EC=4.2.1.152 {ECO:0000269|PubMed:17459323}; DE AltName: Full=Prostaglandin I2 synthase; GN Name=PTGIS; Synonyms=CYP8, CYP8A1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Aorta; RX PubMed=8185632; DOI=10.1006/bbrc.1994.1652; RA Miyata A., Hara S., Yokoyama C., Inoue H., Ullrich V., Tanabe T.; RT "Molecular cloning and expression of human prostacyclin synthase."; RL Biochem. Biophys. Res. Commun. 200:1728-1734(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LEU-38; ARG-118 AND SER-379. RX PubMed=11281454; DOI=10.1007/s004390000444; RA Chevalier D., Cauffiez C., Bernard C., Lo-Guidice J.-M., Allorge D., RA Fazio F., Ferrari N., Libersa C., Lhermitte M., D'Halluin J.C., Broly F.; RT "Characterization of new mutations in the coding sequence and 5'- RT untranslated region of the human prostacyclin synthase gene (CYP8A1)."; RL Hum. Genet. 108:148-155(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; 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 [5] RP INVOLVEMENT IN EHT. RX PubMed=12372404; DOI=10.1016/s0006-291x(02)02341-0; RA Nakayama T., Soma M., Watanabe Y., Hasimu B., Sato M., Aoi N., Kosuge K., RA Kanmatsuse K., Kokubun S., Marrow J.D., Oates J.A.; RT "Splicing mutation of the prostacyclin synthase gene in a family associated RT with hypertension."; RL Biochem. Biophys. Res. Commun. 297:1135-1139(2002). RN [6] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF CYS-441. RX PubMed=15115769; DOI=10.1093/jb/mvh059; RA Wada M., Yokoyama C., Hatae T., Shimonishi M., Nakamura M., Imai Y., RA Ullrich V., Tanabe T.; RT "Purification and characterization of recombinant human prostacyclin RT synthase."; RL J. Biochem. 135:455-463(2004). RN [7] RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=17459323; DOI=10.1016/j.abb.2007.03.012; RA Yeh H.C., Tsai A.L., Wang L.H.; RT "Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by RT human prostacyclin and thromboxane synthases."; RL Arch. Biochem. Biophys. 461:159-168(2007). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, VARIANT RP THR-447, AND CHARACTERIZATION OF VARIANT THR-447. RX PubMed=25623425; DOI=10.1016/j.abb.2015.01.012; RA Cho S.A., Rohn-Glowacki K.J., Jarrar Y.B., Yi M., Kim W.Y., Shin J.G., RA Lee S.J.; RT "Analysis of genetic polymorphism and biochemical characterization of a RT functionally decreased variant in prostacyclin synthase gene (CYP8A1) in RT humans."; RL Arch. Biochem. Biophys. 569C:10-18(2015). RN [9] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 23-500 IN COMPLEX WITH HEME, AND RP COFACTOR. RX PubMed=17020766; DOI=10.1016/j.jmb.2006.09.039; RA Chiang C.W., Yeh H.C., Wang L.H., Chan N.L.; RT "Crystal structure of the human prostacyclin synthase."; RL J. Mol. Biol. 364:266-274(2006). RN [10] RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 18-500 IN COMPLEX WITH HEME AND RP INHIBITOR MINOXIDIL, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=18032380; DOI=10.1074/jbc.m707470200; RA Li Y.C., Chiang C.W., Yeh H.C., Hsu P.Y., Whitby F.G., Wang L.H., RA Chan N.L.; RT "Structures of prostacyclin synthase and its complexes with substrate RT analog and inhibitor reveal a ligand-specific heme conformation change."; RL J. Biol. Chem. 283:2917-2926(2008). 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:18032380, PubMed:25623425, CC PubMed:12372404, PubMed:15115769). Additionally, displays dehydratase CC activity, toward hydroperoxyeicosatetraenoates (HPETEs), especially CC toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)- CC HPETE) (PubMed:17459323). {ECO:0000269|PubMed:12372404, CC ECO:0000269|PubMed:15115769, ECO:0000269|PubMed:17459323, CC ECO:0000269|PubMed:18032380, ECO:0000269|PubMed:25623425}. 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:15115769, ECO:0000269|PubMed:18032380, CC ECO:0000269|PubMed:25623425}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23581; CC Evidence={ECO:0000305|PubMed:15115769, ECO:0000305|PubMed:18032380, CC ECO:0000305|PubMed:25623425}; 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:0000269|PubMed:17459323}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55557; CC Evidence={ECO:0000269|PubMed:17459323}; 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:0000269|PubMed:17459323}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48637; CC Evidence={ECO:0000305|PubMed:17459323}; 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:0000269|PubMed:17459323}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48857; CC Evidence={ECO:0000305|PubMed:17459323}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000269|PubMed:17020766, ECO:0000269|PubMed:18032380}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=9.55 uM for 6-keto-PGF1alpha {ECO:0000269|PubMed:25623425}; CC KM=30 uM for prostaglandin H2 {ECO:0000269|PubMed:15115769}; CC KM=60 uM for (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate CC {ECO:0000269|PubMed:17459323}; CC KM=13 uM for prostaglandin H2 (at 23 degrees Celsius) CC {ECO:0000269|PubMed:18032380}; CC Vmax=534 mmol/min/pg enzyme with prostaglandin H2 as substrate CC {ECO:0000269|PubMed:25623425}; CC Vmax=15 umol/min/mg enzyme with prostaglandin H2 as substrate CC {ECO:0000269|PubMed:15115769}; CC Vmax=980 mol/min/mol enzyme with prostaglandin H2 as substrate CC {ECO:0000269|PubMed:18032380}; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:Q29626}; Single-pass membrane protein CC {ECO:0000255}. CC -!- TISSUE SPECIFICITY: Widely expressed; particularly abundant in ovary, CC heart, skeletal muscle, lung and prostate. CC {ECO:0000269|PubMed:8185632}. CC -!- DISEASE: Essential hypertension (EHT) [MIM:145500]: A condition in CC which blood pressure is consistently higher than normal with no CC identifiable cause. {ECO:0000269|PubMed:12372404}. Note=The disease may CC be caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium; CC Note=CYP8A1 alleles; CC URL="https://www.pharmvar.org/gene/PTGIS"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44219/PTGIS"; 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; D38145; BAA07343.1; -; mRNA. DR EMBL; AF297048; AAG31781.1; -; mRNA. DR EMBL; AF297049; AAG31782.1; -; mRNA. DR EMBL; AF297050; AAG31783.1; -; mRNA. DR EMBL; AF297051; AAG31784.1; -; mRNA. DR EMBL; AF297052; AAG31785.1; -; mRNA. DR EMBL; AL118525; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC101809; AAI01810.1; -; mRNA. DR EMBL; BC101811; AAI01812.1; -; mRNA. DR CCDS; CCDS13419.1; -. DR PIR; JC2231; JC2231. DR RefSeq; NP_000952.1; NM_000961.3. DR PDB; 2IAG; X-ray; 2.15 A; A/B=23-500. DR PDB; 3B6H; X-ray; 1.62 A; A/B=18-500. DR PDBsum; 2IAG; -. DR PDBsum; 3B6H; -. DR AlphaFoldDB; Q16647; -. DR SMR; Q16647; -. DR BioGRID; 111712; 6. DR IntAct; Q16647; 1. DR STRING; 9606.ENSP00000244043; -. DR BindingDB; Q16647; -. DR ChEMBL; CHEMBL4428; -. DR DrugBank; DB08675; (5Z)-7-{(1R,4S,5R,6R)-6-[(1E)-1-Octen-1-yl]-2,3-diazabicyclo[2.2.1]hept-2-en-5-yl}-5-heptenoic acid. DR DrugBank; DB01240; Epoprostenol. DR DrugBank; DB00812; Phenylbutazone. DR DrugCentral; Q16647; -. DR GuidetoPHARMACOLOGY; 1356; -. DR SwissLipids; SLP:000001097; -. DR CarbonylDB; Q16647; -. DR iPTMnet; Q16647; -. DR PhosphoSitePlus; Q16647; -. DR BioMuta; PTGIS; -. DR DMDM; 2493373; -. DR EPD; Q16647; -. DR jPOST; Q16647; -. DR MassIVE; Q16647; -. DR MaxQB; Q16647; -. DR PaxDb; 9606-ENSP00000244043; -. DR PeptideAtlas; Q16647; -. DR ProteomicsDB; 60999; -. DR Pumba; Q16647; -. DR Antibodypedia; 2399; 279 antibodies from 33 providers. DR DNASU; 5740; -. DR Ensembl; ENST00000244043.5; ENSP00000244043.3; ENSG00000124212.6. DR GeneID; 5740; -. DR KEGG; hsa:5740; -. DR MANE-Select; ENST00000244043.5; ENSP00000244043.3; NM_000961.4; NP_000952.1. DR UCSC; uc002xut.4; human. DR AGR; HGNC:9603; -. DR CTD; 5740; -. DR DisGeNET; 5740; -. DR GeneCards; PTGIS; -. DR HGNC; HGNC:9603; PTGIS. DR HPA; ENSG00000124212; Tissue enhanced (fallopian tube, urinary bladder). DR MalaCards; PTGIS; -. DR MIM; 145500; phenotype. DR MIM; 601699; gene. DR neXtProt; NX_Q16647; -. DR OpenTargets; ENSG00000124212; -. DR PharmGKB; PA292; -. DR VEuPathDB; HostDB:ENSG00000124212; -. DR eggNOG; KOG0684; Eukaryota. DR GeneTree; ENSGT00940000153709; -. DR HOGENOM; CLU_018012_1_3_1; -. DR InParanoid; Q16647; -. DR OMA; KFITRMK; -. DR OrthoDB; 1537669at2759; -. DR PhylomeDB; Q16647; -. DR TreeFam; TF105090; -. DR BioCyc; MetaCyc:HS04738-MONOMER; -. DR BRENDA; 5.3.99.4; 2681. DR PathwayCommons; Q16647; -. DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol. DR Reactome; R-HSA-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol. DR Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol. DR Reactome; R-HSA-197264; Nicotinamide salvaging. DR Reactome; R-HSA-211979; Eicosanoids. DR Reactome; R-HSA-211994; Sterols are 12-hydroxylated by CYP8B1. DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX). DR SABIO-RK; Q16647; -. DR SignaLink; Q16647; -. DR BioGRID-ORCS; 5740; 14 hits in 1164 CRISPR screens. DR ChiTaRS; PTGIS; human. DR EvolutionaryTrace; Q16647; -. DR GeneWiki; Prostacyclin_synthase; -. DR GenomeRNAi; 5740; -. DR Pharos; Q16647; Tchem. DR PRO; PR:Q16647; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q16647; Protein. DR Bgee; ENSG00000124212; Expressed in parietal pleura and 169 other cell types or tissues. DR GO; GO:0005901; C:caveola; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA: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:UniProtKB. DR GO; GO:0020037; F:heme binding; IDA: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:UniProtKB. DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB. DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:UniProtKB. DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:UniProtKB. DR GO; GO:0019371; P:cyclooxygenase pathway; TAS:Reactome. DR GO; GO:0006690; P:icosanoid metabolic process; IDA:UniProtKB. DR GO; GO:0034356; P:NAD biosynthesis via nicotinamide riboside salvage pathway; TAS:Reactome. DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IDA:UniProtKB. DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB. DR CDD; cd20634; PGIS_CYP8A1; 1. DR DisProt; DP02578; -. 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 SUPFAM; SSF48264; Cytochrome P450; 1. DR Genevisible; Q16647; HS. PE 1: Evidence at protein level; KW 3D-structure; 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_0000051910" 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:0000269|PubMed:17020766, FT ECO:0000269|PubMed:18032380, ECO:0007744|PDB:2IAG, FT ECO:0007744|PDB:3B6H" FT VARIANT 38 FT /note="P -> L (in allele CYP8A1*2; dbSNP:rs1173082660)" FT /evidence="ECO:0000269|PubMed:11281454" FT /id="VAR_010915" FT VARIANT 118 FT /note="S -> R (in allele CYP8A1*3; dbSNP:rs5622)" FT /evidence="ECO:0000269|PubMed:11281454" FT /id="VAR_010916" FT VARIANT 154 FT /note="E -> A (in dbSNP:rs5623)" FT /id="VAR_014634" FT VARIANT 171 FT /note="F -> L (in dbSNP:rs5624)" FT /id="VAR_014635" FT VARIANT 236 FT /note="R -> C (in dbSNP:rs5626)" FT /id="VAR_014636" FT VARIANT 379 FT /note="R -> S (in allele CYP8A1*4; dbSNP:rs56195291)" FT /evidence="ECO:0000269|PubMed:11281454" FT /id="VAR_010917" FT VARIANT 447 FT /note="A -> T (in allele CYP8A1*5; results in a FT significantly decreased enzyme activity; FT dbSNP:rs146531327)" FT /evidence="ECO:0000269|PubMed:25623425" FT /id="VAR_073186" FT VARIANT 500 FT /note="P -> S (in dbSNP:rs5584)" FT /id="VAR_014637" FT MUTAGEN 441 FT /note="C->H: Abolishes prostaglandin-I synthase activity." FT /evidence="ECO:0000269|PubMed:15115769" FT TURN 38..40 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 43..48 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 50..61 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 63..69 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 72..77 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 80..82 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 83..87 FT /evidence="ECO:0007829|PDB:3B6H" FT TURN 91..93 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 94..96 FT /evidence="ECO:0007829|PDB:2IAG" FT HELIX 98..106 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 117..125 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 130..155 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 160..163 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 164..181 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 190..219 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 224..240 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 243..246 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 254..265 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 270..285 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 288..300 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 303..318 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 333..336 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 339..352 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 357..361 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 365..368 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 374..377 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 382..385 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 388..392 FT /evidence="ECO:0007829|PDB:3B6H" FT TURN 395..397 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 398..400 FT /evidence="ECO:0007829|PDB:3B6H" FT TURN 406..409 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 414..416 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 444..460 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 462..468 FT /evidence="ECO:0007829|PDB:3B6H" FT HELIX 478..480 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 482..485 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 488..490 FT /evidence="ECO:0007829|PDB:3B6H" FT STRAND 493..498 FT /evidence="ECO:0007829|PDB:3B6H" SQ SEQUENCE 500 AA; 57104 MW; 39595442BFC0B625 CRC64; MAWAALLGLL AALLLLLLLS RRRTRRPGEP PLDLGSIPWL GYALDFGKDA ASFLTRMKEK HGDIFTILVG GRYVTVLLDP HSYDAVVWEP RTRLDFHAYA IFLMERIFDV QLPHYSPSDE KARMKLTLLH RELQALTEAM YTNLHAVLLG DATEAGSGWH EMGLLDFSYS FLLRAGYLTL YGIEALPRTH ESQAQDRVHS ADVFHTFRQL DRLLPKLARG SLSVGDKDHM CSVKSRLWKL LSPARLARRA HRSKWLESYL LHLEEMGVSE EMQARALVLQ LWATQGNMGP AAFWLLLFLL KNPEALAAVR GELESILWQA EQPVSQTTTL PQKVLDSTPV LDSVLSESLR LTAAPFITRE VVVDLAMPMA DGREFNLRRG DRLLLFPFLS PQRDPEIYTD PEVFKYNRFL NPDGSEKKDF YKDGKRLKNY NMPWGAGHNH CLGRSYAVNS IKQFVFLVLV HLDLELINAD VEIPEFDLSR YGFGLMQPEH DVPVRYRIRP //