Hematopoietic prostaglandin D synthase

Details

Name
Hematopoietic prostaglandin D synthase
Synonyms
  • 5.3.99.2
  • Glutathione S-transferase
  • Glutathione-dependent PGD synthase
  • Glutathione-requiring prostaglandin D synthase
  • GST class-sigma
  • GSTS
  • H-PGDS
  • PGDS
  • Prostaglandin-H2 D-isomerase
  • PTGDS2
Gene Name
HPGDS
UniProtKB Entry
O60760Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0016335|Hematopoietic prostaglandin D synthase
MPNYKLTYFNMRGRAEIIRYIFAYLDIQYEDHRIEQADWPEIKSTLPFGKIPILEVDGLT
LHQSLAIARYLTKNTDLAGNTEMEQCHVDAIVDTLDDFMSCFPWAEKKQDVKEQMFNELL
TYNAPHLMQDLDTYLGGREWLIGNSVTWADFYWEICSTTLLVFKPDLLDNHPRLVTLRKK
VQAIPAVANWIKRRPQTKL
Number of residues
199
Molecular Weight
23343.65
Theoretical pI
5.64
GO Classification
Processes
prostaglandin biosynthetic process
Components
intracellular membrane-bounded organelle / nucleoplasm
General Function
Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides and organic isothiocyanates. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide
Specific Function
calcium ion binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016336|Hematopoietic prostaglandin D synthase (HPGDS)
ATGCCAAACTACAAACTCACTTATTTTAATATGAGGGGGAGAGCAGAAATTATTCGTTAC
ATATTTGCTTATTTGGACATACAGTATGAAGACCACAGAATAGAACAAGCTGACTGGCCT
GAAATCAAATCAACTCTCCCATTTGGAAAAATCCCCATTTTGGAAGTTGATGGACTTACT
CTTCACCAGAGCCTAGCAATAGCAAGATATTTGACCAAAAACACAGATTTGGCTGGAAAC
ACAGAAATGGAACAATGTCATGTTGATGCTATTGTGGACACTCTGGATGATTTCATGTCA
TGTTTTCCTTGGGCAGAGAAAAAGCAAGATGTGAAAGAGCAGATGTTCAATGAGCTGCTC
ACGTATAATGCGCCTCATCTTATGCAAGACTTGGACACATATTTAGGGGGGAGAGAATGG
CTTATTGGTAACTCTGTAACTTGGGCAGACTTCTACTGGGAGATTTGCAGTACCACACTT
TTGGTCTTTAAGCCTGACCTGTTAGACAACCATCCAAGGCTGGTGACTTTACGGAAGAAA
GTCCAAGCCATTCCTGCCGTCGCTAACTGGATAAAACGAAGGCCCCAAACCAAACTCTAG
Chromosome Location
4
Locus
4q22.3
External Identifiers
ResourceLink
UniProtKB IDO60760
UniProtKB Entry NameHPGDS_HUMAN
GenBank Protein ID3046817
GenBank Gene IDD82073
GeneCard IDHPGDS
HGNC IDHGNC:17890
PDB ID(s)1IYH, 1IYI, 1V40, 2CVD, 2VCQ, 2VCW, 2VCX, 2VCZ, 2VD0, 2VD1, 3EE2, 3KXO, 3VI5, 3VI7, 4EC0, 4EDY, 4EDZ, 4EE0, 5AIS, 5AIV, 5AIX, 5YWE, 5YWX, 5YX1, 6N4E, 6W58, 6W8H, 6ZTC, 7JR6, 7JR8
KEGG IDhsa:27306
IUPHAR/Guide To Pharmacology ID1381
NCBI Gene ID27306
General References
  1. Kanaoka Y, Fujimori K, Kikuno R, Sakaguchi Y, Urade Y, Hayaishi O: Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase. Conservation of the ancestral genomic structure of sigma-class glutathione S-transferase. Eur J Biochem. 2000 Jun;267(11):3315-22. [Article]
  2. Jowsey IR, Thomson AM, Flanagan JU, Murdock PR, Moore GB, Meyer DJ, Murphy GJ, Smith SA, Hayes JD: Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases. Biochem J. 2001 Nov 1;359(Pt 3):507-16. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [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. Suzuki T, Watanabe K, Kanaoka Y, Sato T, Hayaishi O: Induction of hematopoietic prostaglandin D synthase in human megakaryocytic cells by phorbol ester. Biochem Biophys Res Commun. 1997 Dec 18;241(2):288-93. [Article]
  6. Mahmud I, Ueda N, Yamaguchi H, Yamashita R, Yamamoto S, Kanaoka Y, Urade Y, Hayaishi O: Prostaglandin D synthase in human megakaryoblastic cells. J Biol Chem. 1997 Nov 7;272(45):28263-6. [Article]
  7. Inoue T, Irikura D, Okazaki N, Kinugasa S, Matsumura H, Uodome N, Yamamoto M, Kumasaka T, Miyano M, Kai Y, Urade Y: Mechanism of metal activation of human hematopoietic prostaglandin D synthase. Nat Struct Biol. 2003 Apr;10(4):291-6. [Article]
  8. Inoue T, Okano Y, Kado Y, Aritake K, Irikura D, Uodome N, Okazaki N, Kinugasa S, Shishitani H, Matsumura H, Kai Y, Urade Y: First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase. J Biochem. 2004 Mar;135(3):279-83. [Article]
  9. Aritake K, Kado Y, Inoue T, Miyano M, Urade Y: Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase. J Biol Chem. 2006 Jun 2;281(22):15277-86. Epub 2006 Mar 17. [Article]
  10. Hohwy M, Spadola L, Lundquist B, Hawtin P, Dahmen J, Groth-Clausen I, Nilsson E, Persdotter S, von Wachenfeldt K, Folmer RH, Edman K: Novel prostaglandin D synthase inhibitors generated by fragment-based drug design. J Med Chem. 2008 Apr 10;51(7):2178-86. doi: 10.1021/jm701509k. Epub 2008 Mar 15. [Article]
  11. Weber JE, Oakley AJ, Christ AN, Clark AG, Hayes JD, Hall R, Hume DA, Board PG, Smythe ML, Flanagan JU: Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase. Eur J Med Chem. 2010 Feb;45(2):447-54. doi: 10.1016/j.ejmech.2009.10.025. Epub 2009 Oct 23. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Hematopoietic prostaglandin D synthase (Humans)protein
primary
Glutathione S-transferases (Cytosolic) (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
2-(2f-Benzothiazolyl)-5-Styryl-3-(4f-Phthalhydrazidyl)Tetrazolium ChlorideexperimentalunknowntargetDetails
Glutathioneapproved, investigational, nutraceuticalunknowntargetDetails
3-phenyl-5-(1H-pyrazol-3-yl)isoxazoleexperimentalunknowntargetDetails
PHENYL-5-(1H-PYRAZOL-3-YL)-1,3-THIAZOLEexperimentalunknowntargetDetails
TranilastinvestigationalunknowntargetinhibitorDetails
4-{[4-(4-fluoro-3-methylphenyl)-1,3-thiazol-2-yl]amino}-2-hydroxybenzoic acidexperimentalunknowntargetDetails
4-(BENZHYDRYLOXY)-1-[3-(1H-TETRAAZOL-5-YL)PROPYL]PIPERIDINEexperimentalyestargetinhibitorDetails
NocodazoleexperimentalunknowntargetDetails
3-(4-nitrophenyl)-1H-pyrazoleexperimentalunknowntargetDetails
1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC ACIDexperimentalunknowntargetDetails
Formic acidexperimental, investigationalyestargetinhibitorDetails
ProtoporphyrinexperimentalyestargetinhibitorDetails
S-HexylglutathioneexperimentalyestargetinhibitorDetails
Cibacron BlueexperimentalyestargetinhibitorDetails
7-beta-HydroxyepiandrosteroneinvestigationalyestargetstimulatorDetails
Praziquantelapproved, investigational, vet_approvedyestargetinhibitorDetails
Glutathione disulfideapproved, experimental, investigationalunknowntargetactivatorDetails
Deoxycholic acidapprovedunknowntargetinhibitorDetails
AmitriptylineapprovedunknownenzymeinhibitorDetails
ChlorambucilapprovedunknownenzymesubstrateDetails