Prostacyclin synthase

Details

Name
Prostacyclin synthase
Synonyms
  • 5.3.99.4
  • CYP8
  • CYP8A1
  • Prostaglandin I2 synthase
Gene Name
PTGIS
Organism
Humans
Amino acid sequence
>lcl|BSEQ0018917|Prostacyclin synthase
MAWAALLGLLAALLLLLLLSRRRTRRPGEPPLDLGSIPWLGYALDFGKDAASFLTRMKEK
HGDIFTILVGGRYVTVLLDPHSYDAVVWEPRTRLDFHAYAIFLMERIFDVQLPHYSPSDE
KARMKLTLLHRELQALTEAMYTNLHAVLLGDATEAGSGWHEMGLLDFSYSFLLRAGYLTL
YGIEALPRTHESQAQDRVHSADVFHTFRQLDRLLPKLARGSLSVGDKDHMCSVKSRLWKL
LSPARLARRAHRSKWLESYLLHLEEMGVSEEMQARALVLQLWATQGNMGPAAFWLLLFLL
KNPEALAAVRGELESILWQAEQPVSQTTTLPQKVLDSTPVLDSVLSESLRLTAAPFITRE
VVVDLAMPMADGREFNLRRGDRLLLFPFLSPQRDPEIYTDPEVFKYNRFLNPDGSEKKDF
YKDGKRLKNYNMPWGAGHNHCLGRSYAVNSIKQFVFLVLVHLDLELINADVEIPEFDLSR
YGFGLMQPEHDVPVRYRIRP
Number of residues
500
Molecular Weight
57103.385
Theoretical pI
7.33
GO Classification
Functions
heme binding / iron ion binding / monooxygenase activity / oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen / prostaglandin-I synthase activity
Processes
apoptotic signaling pathway / arachidonic acid metabolic process / cellular response to hypoxia / cellular response to interleukin-1 / cellular response to interleukin-6 / cyclooxygenase pathway / decidualization / embryo implantation / icosanoid metabolic process / NAD metabolic process / negative regulation of inflammatory response / negative regulation of NF-kappaB transcription factor activity / negative regulation of nitric oxide biosynthetic process / nicotinamide metabolic process / positive regulation of angiogenesis / positive regulation of execution phase of apoptosis / positive regulation of peroxisome proliferator activated receptor signaling pathway / prostaglandin biosynthetic process / small molecule metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process / xenobiotic metabolic process
Components
caveola / endoplasmic reticulum / endoplasmic reticulum membrane / extracellular space / integral component of membrane / nucleus
General Function
Prostaglandin-i synthase activity
Specific Function
Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).
Pfam Domain Function
Transmembrane Regions
1-20
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0018918|Prostacyclin synthase (PTGIS)
ATGGCTTGGGCCGCGCTCCTCGGCCTCCTGGCCGCACTGTTGCTGCTGCTGCTACTGAGC
CGCCGCCGCACGCGGCGACCTGGTGAGCCTCCCCTGGACCTGGGCAGCATCCCCTGGTTG
GGGTATGCCTTGGACTTTGGAAAAGATGCTGCCAGCTTCCTCACGAGGATGAAGGAGAAG
CACGGTGACATCTTTACTATACTGGTTGGGGGCAGGTATGTCACCGTTCTCCTGGACCCA
CACTCCTACGACGCGGTGGTGTGGGAGCCTCGCACCAGGCTCGACTTCCATGCCTATGCC
ATCTTCCTCATGGAGAGGATTTTTGATGTGCAGCTTCCACATTACAGCCCCAGTGATGAA
AAGGCCAGGATGAAACTGACTCTTCTCCACAGAGAGCTCCAGGCACTCACAGAAGCCATG
TATACCAACCTCCATGCAGTGCTGTTGGGCGATGCTACAGAAGCAGGCAGTGGCTGGCAC
GAGATGGGTCTCCTCGACTTCTCCTACAGCTTCCTGCTCAGAGCCGGCTACCTGACTCTT
TACGGAATTGAGGCGCTGCCACGCACCCATGAAAGCCAGGCCCAGGACCGCGTCCACTCA
GCTGATGTCTTCCACACCTTTCGCCAGCTCGACCGGCTGCTCCCCAAACTGGCCCGTGGC
TCCCTGTCAGTGGGGGACAAGGACCACATGTGCAGTGTCAAAAGTCGCCTGTGGAAGCTG
CTATCCCCAGCCAGGCTGGCCAGGCGGGCCCACCGGAGCAAATGGCTGGAGAGTTACCTG
CTGCACCTGGAGGAGATGGGTGTGTCAGAGGAGATGCAGGCACGGGCCCTGGTGCTGCAG
CTGTGGGCCACACAGGGGAATATGGGTCCCGCTGCCTTCTGGCTCCTGCTCTTCCTTCTC
AAGAATCCTGAAGCCCTGGCTGCTGTCCGCGGAGAGCTCGAGAGTATCCTTTGGCAAGCG
GAGCAGCCTGTCTCGCAGACGACCACTCTCCCACAGAAGGTTCTAGACAGCACACCTGTG
CTTGATAGCGTGCTGAGTGAGAGCCTCAGGCTTACAGCTGCCCCCTTCATCACCCGCGAG
GTTGTGGTGGACCTGGCCATGCCCATGGCAGACGGGCGAGAATTCAACCTGCGACGTGGT
GACCGCCTCCTCCTCTTCCCCTTCCTGAGCCCCCAGAGAGACCCAGAAATCTACACAGAC
CCAGAGGTATTTAAATACAACCGATTCCTGAACCCTGACGGATCAGAGAAGAAAGACTTT
TACAAGGATGGGAAACGGCTGAAGAATTACAACATGCCCTGGGGGGCGGGGCACAATCAC
TGCCTGGGGAGGAGTTATGCGGTCAACAGCATCAAACAATTTGTGTTCCTTGTGCTGGTG
CACTTGGACTTGGAGCTGATCAACGCAGATGTGGAGATCCCTGAGTTTGACCTCAGCAGG
TACGGCTTCGGTCTGATGCAGCCGGAACACGACGTGCCCGTCCGCTACCGCATCCGCCCA
TGA
Chromosome Location
20
Locus
20q13.13
External Identifiers
ResourceLink
UniProtKB IDQ16647
UniProtKB Entry NamePTGIS_HUMAN
GenBank Protein ID10944956
GenBank Gene IDD38145
GenAtlas IDPTGIS
HGNC IDHGNC:9603
General References
  1. Miyata A, Hara S, Yokoyama C, Inoue H, Ullrich V, Tanabe T: Molecular cloning and expression of human prostacyclin synthase. Biochem Biophys Res Commun. 1994 May 16;200(3):1728-34. [Article]
  2. Chevalier D, Cauffiez C, Bernard C, Lo-Guidice JM, Allorge D, Fazio F, Ferrari N, Libersa C, Lhermitte M, D'Halluin JC, Broly F: Characterization of new mutations in the coding sequence and 5'-untranslated region of the human prostacylcin synthase gene (CYP8A1). Hum Genet. 2001 Feb;108(2):148-55. [Article]
  3. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Nakayama T, Soma M, Watanabe Y, Hasimu B, Sato M, Aoi N, Kosuge K, Kanmatsuse K, Kokubun S, Marrow JD, Oates JA: Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. Biochem Biophys Res Commun. 2002 Oct 11;297(5):1135-9. [Article]
  6. Cho SA, Rohn-Glowacki KJ, Jarrar YB, Yi M, Kim WY, Shin JG, Lee SJ: Analysis of genetic polymorphism and biochemical characterization of a functionally decreased variant in prostacyclin synthase gene (CYP8A1) in humans. Arch Biochem Biophys. 2015 Mar 1;569:10-8. doi: 10.1016/j.abb.2015.01.012. Epub 2015 Jan 23. [Article]
  7. Chiang CW, Yeh HC, Wang LH, Chan NL: Crystal structure of the human prostacyclin synthase. J Mol Biol. 2006 Dec 1;364(3):266-74. Epub 2006 Sep 20. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00812Phenylbutazoneapproved, vet_approvedyesinhibitorDetails
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 acidexperimentalunknownDetails
DB01240EpoprostenolapprovedyesinducerDetails