PTGIS_DANRE
ID PTGIS_DANRE Reviewed; 480 AA.
AC F1RE08; A1XBQ5; A9LLA5;
DT 07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Prostacyclin synthase {ECO:0000303|PubMed:18032380};
DE EC=5.3.99.4 {ECO:0000269|PubMed:18032380};
DE AltName: Full=Hydroperoxy icosatetraenoate dehydratase;
DE EC=4.2.1.152 {ECO:0000250|UniProtKB:Q16647};
DE AltName: Full=Prostaglandin I2 synthase {ECO:0000303|PubMed:18032380};
DE Short=PGIS {ECO:0000303|PubMed:18032380};
GN Name=ptgis {ECO:0000312|ZFIN:ZDB-GENE-070116-1};
GN Synonyms=ptgisl {ECO:0000312|ZFIN:ZDB-GENE-070116-1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|Proteomes:UP000000437};
RN [1] {ECO:0007744|PDB:3B98, ECO:0007744|PDB:3B99}
RP NUCLEOTIDE SEQUENCE [MRNA], X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF
RP 17-480 IN COMPLEX WITH HEME AND SUBSTRATE ANALOG U51605, FUNCTION,
RP CATALYTIC ACTIVITY, COFACTOR, AND 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).
RN [2] {ECO:0000312|EMBL:ABC59225.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lee D.S., Nioche P., Herzog W., Hunt R.D., Stainier D., Raman C.;
RT "Role of prostacyclin in vasculogenesis and a structural-mechanism for its
RT biosynthesis.";
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Catalyzes the isomerization of prostaglandin H2 to
CC prostacyclin (= prostaglandin I2). {ECO:0000269|PubMed:18032380}.
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). Additionally, displays
CC dehydratase activity, toward hydroperoxyeicosatetraenoates (HPETEs),
CC especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate
CC (15(S)-HPETE) (By similarity). {ECO:0000250|UniProtKB:Q16647,
CC ECO:0000269|PubMed:18032380}.
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:18032380};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23581;
CC Evidence={ECO:0000305|PubMed:18032380};
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:0000255|PIRNR:PIRNR000047,
CC ECO:0000255|PIRSR:PIRSR000047-1, ECO:0000269|PubMed:18032380};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=25 uM for prostaglandin H2 (at 23 degrees Celsius)
CC {ECO:0000269|PubMed:18032380};
CC Vmax=1100 mol/min/mol enzyme (at 23 degrees Celsius)
CC {ECO:0000269|PubMed:18032380};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q29626, ECO:0000255|PIRNR:PIRNR000047}; Single-
CC pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family.
CC {ECO:0000255|PIRNR:PIRNR000047, ECO:0000305}.
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DR EMBL; EU236593; ABX51998.1; -; mRNA.
DR EMBL; DQ324855; ABC59225.1; -; mRNA.
DR EMBL; BX546446; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001104630.1; NM_001111160.1.
DR PDB; 3B98; X-ray; 2.08 A; A/B=17-480.
DR PDB; 3B99; X-ray; 2.50 A; A/B=17-480.
DR PDBsum; 3B98; -.
DR PDBsum; 3B99; -.
DR AlphaFoldDB; F1RE08; -.
DR SMR; F1RE08; -.
DR STRING; 7955.ENSDARP00000078769; -.
DR PaxDb; F1RE08; -.
DR Ensembl; ENSDART00000084334; ENSDARP00000078769; ENSDARG00000060094.
DR Ensembl; ENSDART00000180836; ENSDARP00000156731; ENSDARG00000113227.
DR GeneID; 559148; -.
DR KEGG; dre:559148; -.
DR CTD; 5740; -.
DR ZFIN; ZDB-GENE-070116-1; ptgis.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153709; -.
DR HOGENOM; CLU_018012_1_3_1; -.
DR InParanoid; F1RE08; -.
DR OMA; ARMKDKH; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; F1RE08; -.
DR TreeFam; TF105090; -.
DR Reactome; R-DRE-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-DRE-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-DRE-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-DRE-197264; Nicotinamide salvaging.
DR Reactome; R-DRE-211979; Eicosanoids.
DR Reactome; R-DRE-211994; Sterols are 12-hydroxylated by CYP8B1.
DR Reactome; R-DRE-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR PRO; PR:F1RE08; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 6.
DR Bgee; ENSDARG00000060094; Expressed in pharyngeal gill and 15 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
DR DisProt; DP02884; -.
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 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..480
FT /note="Prostacyclin synthase"
FT /id="PRO_0000440095"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 104
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18032380"
FT BINDING 110
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18032380"
FT BINDING 277
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18032380"
FT BINDING 338..339
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18032380"
FT BINDING 362
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18032380"
FT BINDING 421
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:0000255|PIRSR:PIRSR000047-1,
FT ECO:0000269|PubMed:18032380, ECO:0007744|PDB:3B98,
FT ECO:0007744|PDB:3B99"
FT CONFLICT 186
FT /note="D -> N (in Ref. 1; ABX51998 and 2; ABC59225)"
FT /evidence="ECO:0000305"
FT CONFLICT 212
FT /note="I -> V (in Ref. 1; ABX51998 and 2; ABC59225)"
FT /evidence="ECO:0000305"
FT CONFLICT 348
FT /note="R -> C (in Ref. 1; ABX51998)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="E -> D (in Ref. 2; ABC59225)"
FT /evidence="ECO:0000305"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 49..60
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 71..76
FT /evidence="ECO:0007829|PDB:3B98"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 82..86
FT /evidence="ECO:0007829|PDB:3B98"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 95..104
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 115..125
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 128..145
FT /evidence="ECO:0007829|PDB:3B98"
FT TURN 148..152
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:3B99"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 163..180
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 187..208
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 214..231
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 245..255
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 260..275
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 278..290
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 293..303
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 319..332
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 337..341
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 345..348
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 354..357
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 368..372
FT /evidence="ECO:0007829|PDB:3B98"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:3B98"
FT TURN 386..389
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 401..404
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 424..441
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 442..448
FT /evidence="ECO:0007829|PDB:3B98"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 462..465
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:3B98"
FT STRAND 473..478
FT /evidence="ECO:0007829|PDB:3B98"
SQ SEQUENCE 480 AA; 55308 MW; E7C896F114F9540D CRC64;
MMWTALLLVG LSILVIVLYG RRTRRRNEPP LDKGMIPWLG HALEFGKDAA KFLTRMKEKH
GDIFTVRAAG LYITVLLDSN CYDAVLSDVA SLDQTSYAQV LMKRIFNMIL PSHNPESEKK
RAEMHFQGAS LTQLSNSMQN NLRLLMTPSE MGLKTSEWKK DGLFNLCYSL LFKTGYLTVF
GAENNDSAAL TQIYEEFRRF DKLLPKLART TINKEEKQIA SAAREKLWKW LTPSGLDRKP
REQSWLGSYV KQLQDEGIDA EMQRRAMLLQ LWVTQGNAGP AAFWVMGYLL THPEALRAVR
EEIQGGKHLR LEERQKNTPV FDSVLWETLR LTAAALITRD VTQDKKIRLS NGQEYHLRRG
DRLCVFPFIS PQMDPQIHQQ PEMFQFDRFL NADRTEKKDF FKNGARVKYP SVPWGTEDNL
CPGRHFAVHA IKELVFTILT RFDVELCDKN ATVPLVDPSR YGFGILQPAG DLEIRYRIRF
