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O60760 (HPGDS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hematopoietic prostaglandin D synthase

Short name=H-PGDS
EC=5.3.99.2
Alternative name(s):
GST class-sigma
Glutathione S-transferase
EC=2.5.1.18
Glutathione-dependent PGD synthase
Glutathione-requiring prostaglandin D synthase
Prostaglandin-H2 D-isomerase
Gene names
Name:HPGDS
Synonyms:GSTS, PGDS, PTGDS2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length199 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

Catalytic activity

(5Z,13E,15S)-9-alpha,11-alpha-epidioxy-15-hydroxyprosta-5,13-dienoate = (5Z,13E,15S)-9-alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

RX + glutathione = HX + R-S-glutathione. Ref.1 Ref.2 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.13

Cofactor

Glutathione. Required for the prostaglandin D synthase activity. Ref.1 Ref.2 Ref.7 Ref.8

Enzyme regulation

Prostaglandin PGD2 synthesis is stimulated by calcium and magnesium ions. One calcium or magnesium ion is bound between the subunits of the homodimer. The interactions with the protein are for the most part mediated via water molecules. Magnesium increases the affinity for glutathione, while calcium has no effect on the affinity for glutathione. Ref.9

Subunit structure

Homodimer. Ref.9 Ref.10 Ref.12

Subcellular location

Cytoplasm Ref.8.

Tissue specificity

Expressed in a number of megakaryocytic cell lines but not in platelets. Highly expressed in adipose tissue, macrophages and placenta. Also expressed at lower levels in lung, heart, lymph nodes, appendix, bone marrow and fetal liver. Ref.1 Ref.2 Ref.7 Ref.8

Developmental stage

Highest levels in immature megakaryocytic cells. Disappears after final differentiation to platelets. Ref.7

Induction

By 12-O-tetradecanoylphorbol-13-acetate (TPA). Ref.7 Ref.9

Sequence similarities

Belongs to the GST superfamily. Sigma family.

Contains 1 GST C-terminal domain.

Contains 1 GST N-terminal domain.

Biophysicochemical properties

Kinetic parameters:

KM=8 mM for glutathione for the glutathione-conjugating activity Ref.2 Ref.9 Ref.10

KM=0.6 mM for glutathione for the prostaglandin D synthase activity in the presence of EDTA

KM=0.14 mM for glutathione for the prostaglandin D synthase activity in the presence of magnesium ions

Vmax=8.6 µmol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate

Vmax=5.1 µmol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate

Vmax=44.3 µmol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate

Vmax=10.7 µmol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate

Vmax=6.8 µmol/min/mg enzyme with allyl isothiocyanate as substrate

Vmax=6.3 µmol/min/mg enzyme with benzyl isothiocyanate as substrate

Vmax=0.05 µmol/min/mg enzyme with cumene hydroperoxide as substrate

Ontologies

Keywords
   Biological processFatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Prostaglandin biosynthesis
Prostaglandin metabolism
   Cellular componentCytoplasm
   LigandCalcium
Magnesium
Metal-binding
   Molecular functionIsomerase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Traceable author statement. Source: Reactome

cyclooxygenase pathway

Traceable author statement. Source: Reactome

glutathione derivative biosynthetic process

Traceable author statement. Source: Reactome

locomotory behavior

Traceable author statement PubMed 10781097. Source: ProtInc

prostaglandin metabolic process

Inferred from direct assay Ref.9. Source: UniProtKB

signal transduction

Non-traceable author statement Ref.8. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Traceable author statement Ref.8. Source: ProtInc

cytosol

Traceable author statement. Source: Reactome

   Molecular_functioncalcium ion binding

Inferred from direct assay Ref.9. Source: UniProtKB

glutathione transferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

magnesium ion binding

Inferred from direct assay Ref.9. Source: UniProtKB

prostaglandin-D synthase activity

Inferred from direct assay Ref.9. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 199199Hematopoietic prostaglandin D synthase
PRO_0000185934

Regions

Domain2 – 7978GST N-terminal
Domain81 – 199119GST C-terminal
Region63 – 642Glutathione binding

Sites

Binding site81Glutathione
Binding site141Glutathione
Binding site391Glutathione
Binding site511Glutathione; via amide nitrogen and carbonyl oxygen

Experimental info

Mutagenesis931D → N: Loss of activation by calcium or magnesium ions. Ref.9
Mutagenesis961D → N: Increases PGD2 synthesis. Loss of activation by calcium or magnesium ions. Ref.9
Mutagenesis971D → N: Reduces PGD2 synthesis by 99%. Loss of activation by calcium or magnesium ions. Ref.9
Sequence conflict1871V → I no nucleotide entry Ref.2

Secondary structure

.................................... 199
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O60760 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: A4ED2476B16CC5C3

FASTA19923,344
        10         20         30         40         50         60 
MPNYKLTYFN MRGRAEIIRY IFAYLDIQYE DHRIEQADWP EIKSTLPFGK IPILEVDGLT 

        70         80         90        100        110        120 
LHQSLAIARY LTKNTDLAGN TEMEQCHVDA IVDTLDDFMS CFPWAEKKQD VKEQMFNELL 

       130        140        150        160        170        180 
TYNAPHLMQD LDTYLGGREW LIGNSVTWAD FYWEICSTTL LVFKPDLLDN HPRLVTLRKK 

       190 
VQAIPAVANW IKRRPQTKL 

« Hide

References

« Hide 'large scale' references
[1]"Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase."
Kanaoka Y., Fujimori K., Kikuno R., Sakaguchi Y., Urade Y., Hayaishi O.
Eur. J. Biochem. 267:3315-3322(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY.
Tissue: Placenta.
[2]"Mammalian class Sigma glutathione S-transferases: catalytic properties and tissue-specific expression of human and rat GSH-dependent prostaglandin D2 synthases."
Jowsey I.R., Thomson A.M., Flanagan J.U., Murdock P.R., Moore G.B., Meyer D.J., Murphy G.J., Smith S.A., Hayes J.D.
Biochem. J. 359:507-516(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY.
Tissue: Placenta.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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 T.-O., 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Substantia nigra.
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[7]"Induction of hematopoietic prostaglandin D synthase in human megakaryocytic cells by phorbol ester."
Suzuki T., Watanabe K., Kanaoka Y., Sato T., Hayaishi O.
Biochem. Biophys. Res. Commun. 241:288-293(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, INDUCTION.
Tissue: Megakaryocyte.
[8]"Prostaglandin D synthase in human megakaryoblastic cells."
Mahmud I., Ueda N., Yamaguchi H., Yamashita R., Yamamoto S., Kanaoka Y., Urade Y., Hayaishi O.
J. Biol. Chem. 272:28263-28266(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Megakaryocyte.
[9]"Mechanism of metal activation of human hematopoietic prostaglandin D synthase."
Inoue T., Irikura D., Okazaki N., Kinugasa S., Matsumura H., Uodome N., Yamamoto M., Kumasaka T., Miyano M., Kai Y., Urade Y.
Nat. Struct. Biol. 10:291-296(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEXES WITH CALCIUM IONS; MAGNESIUM IONS AND GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ASP-93; ASP-96 AND ASP-97.
[10]"First determination of the inhibitor complex structure of human hematopoietic prostaglandin D synthase."
Inoue T., Okano Y., Kado Y., Aritake K., Irikura D., Uodome N., Okazaki N., Kinugasa S., Shishitani H., Matsumura H., Kai Y., Urade Y.
J. Biochem. 135:279-283(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH MAGNESIUM IONS AND THE SYNTHETIC INHIBITOR BSBT, FUNCTION, SUBUNIT, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[11]"Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase."
Aritake K., Kado Y., Inoue T., Miyano M., Urade Y.
J. Biol. Chem. 281:15277-15286(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE; MAGNESIUM IONS AND THE SYNTHETIC INHIBITOR HQL-79, FUNCTION, CATALYTIC ACTIVITY.
[12]"Novel prostaglandin D synthase inhibitors generated by fragment-based drug design."
Hohwy M., Spadola L., Lundquist B., Hawtin P., Dahmen J., Groth-Clausen I., Nilsson E., Persdotter S., von Wachenfeldt K., Folmer R.H., Edman K.
J. Med. Chem. 51:2178-2186(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEXES WITH SYNTHETIC INHIBITORS, SUBUNIT.
[13]"Identification and characterisation of new inhibitors for the human hematopoietic prostaglandin D2 synthase."
Weber J.E., Oakley A.J., Christ A.N., Clark A.G., Hayes J.D., Hall R., Hume D.A., Board P.G., Smythe M.L., Flanagan J.U.
Eur. J. Med. Chem. 45:447-454(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR, CATALYTIC ACTIVITY, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D82073 mRNA. Translation: BAA25545.1.
AB008830 Genomic DNA. Translation: BAA96854.1.
AK290075 mRNA. Translation: BAF82764.1.
CR541662 mRNA. Translation: CAG46463.1.
CR541679 mRNA. Translation: CAG46480.1.
CH471057 Genomic DNA. Translation: EAX06052.1.
BC020734 mRNA. Translation: AAH20734.1.
CCDSCCDS3640.1.
RefSeqNP_055300.1. NM_014485.2.
UniGeneHs.128433.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IYHX-ray1.70A/B/C/D2-199[»]
1IYIX-ray1.80A/B/C/D2-199[»]
1V40X-ray1.90A/B/C/D2-199[»]
2CVDX-ray1.45A/B/C/D2-199[»]
2VCQX-ray1.95A/B/C/D1-199[»]
2VCWX-ray1.95A/B/C/D1-199[»]
2VCXX-ray2.10A/B/C/D1-199[»]
2VCZX-ray1.95A/B/C/D1-199[»]
2VD0X-ray2.20A/B/C/D1-199[»]
2VD1X-ray2.25A/B/C/D1-199[»]
3EE2X-ray1.91A/B1-199[»]
3KXOX-ray2.10A/B1-199[»]
3VI5X-ray2.00A/B/C/D2-199[»]
3VI7X-ray2.00A/B/C/D2-199[»]
4EC0X-ray1.85A/B1-199[»]
4EDYX-ray1.72A/B2-199[»]
4EDZX-ray2.00A/B/C/D2-199[»]
4EE0X-ray1.75A/B2-199[»]
ProteinModelPortalO60760.
SMRO60760. Positions 2-199.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118128. 1 interaction.
STRING9606.ENSP00000295256.

Chemistry

BindingDBO60760.
ChEMBLCHEMBL5879.
DrugBankDB00143. Glutathione.
GuidetoPHARMACOLOGY1381.

PTM databases

PhosphoSiteO60760.

Proteomic databases

PaxDbO60760.
PRIDEO60760.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000295256; ENSP00000295256; ENSG00000163106.
GeneID27306.
KEGGhsa:27306.
UCSCuc003hte.1. human.

Organism-specific databases

CTD27306.
GeneCardsGC04M095219.
HGNCHGNC:17890. HPGDS.
HPACAB020805.
HPA024035.
MIM602598. gene.
neXtProtNX_O60760.
PharmGKBPA165664133.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG122057.
HOGENOMHOG000115733.
HOVERGENHBG105321.
InParanoidO60760.
KOK01830.
OMAMSCFPWA.
OrthoDBEOG78WKT1.
PhylomeDBO60760.
TreeFamTF105321.

Enzyme and pathway databases

BioCycMetaCyc:HS08788-MONOMER.
ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO60760.
BgeeO60760.
GenevestigatorO60760.

Family and domain databases

Gene3D1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamPF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]
SUPFAMSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60760.
GeneWikiPGDS.
GenomeRNAi27306.
NextBio50305.
PROO60760.
SOURCESearch...

Entry information

Entry nameHPGDS_HUMAN
AccessionPrimary (citable) accession number: O60760
Secondary accession number(s): Q6FHT9
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 137 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM