PTGIS_HUMAN
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 03-AUG-2022, entry version 197.
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 (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: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="http://atlasgeneticsoncology.org/Genes/PTGISID44219ch20q13.html";
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; 5.
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; Q16647; -.
DR PeptideAtlas; Q16647; -.
DR PRIDE; Q16647; -.
DR ProteomicsDB; 60999; -.
DR Antibodypedia; 2399; 238 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 CTD; 5740; -.
DR DisGeNET; 5740; -.
DR GeneCards; PTGIS; -.
DR HGNC; HGNC:9603; PTGIS.
DR HPA; ENSG00000124212; Tissue enhanced (endometrium, fallopian tube, urinary bladder).
DR MalaCards; PTGIS; -.
DR MIM; 145500; phenotype.
DR MIM; 601699; gene.
DR neXtProt; NX_Q16647; -.
DR OpenTargets; ENSG00000124212; -.
DR Orphanet; 243761; NON RARE IN EUROPE: Essential hypertension.
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; EPQKYKY; -.
DR OrthoDB; 454773at2759; -.
DR PhylomeDB; Q16647; -.
DR TreeFam; TF105090; -.
DR BioCyc; MetaCyc:HS04738-MON; -.
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; 13 hits in 1077 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 167 other tissues.
DR Genevisible; Q16647; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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 DisProt; DP02578; -.
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 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
