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O35543 (HPGDS_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

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.5 Ref.6

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.5 Ref.6

RX + glutathione = HX + R-S-glutathione. Ref.1 Ref.2 Ref.5 Ref.6

Cofactor

Glutathione. Required for the prostaglandin D synthase activity. Ref.2 Ref.5

Subunit structure

Homodimer. Ref.1

Subcellular location

Cytoplasm.

Tissue specificity

Highly expressed in spleen and bone marrow. Lower levels of expression in small intestine, colon, liver, pancreas and skin. Not detected in brain, heart, lung or kidney (at protein level). Ref.1 Ref.2

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=100 µM for glutathione for the prostaglandin D synthase activity Ref.2 Ref.5

KM=500 µM for glutathione for the glutathione-conjugating activity

KM=500 µM for PGH2 for the prostaglandin D synthase activity

KM=3 mM for 1-chloro-2,4-dinitrobenzene

Vmax=17.6 µmol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate

Vmax=9.2 µmol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate

Vmax=48.3 µmol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate

Vmax=17.9 µmol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate

Vmax=0.35 µmol/min/mg enzyme with cumene hydroperoxide as substrate

Vmax=10.2 µmol/min/mg enzyme with allyl isothiocyanate as substrate

Vmax=11.3 µmol/min/mg enzyme with benzyl isothiocyanate as substrate

Sequence caution

The sequence AAB72099.1 differs from that shown. Reason: Frameshift at positions 73 and 113.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 199199Hematopoietic prostaglandin D synthase
PRO_0000185936

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

Mutagenesis81Y → F: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5
Mutagenesis141R → E: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5
Mutagenesis141R → K: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5
Mutagenesis1041W → I: No significant effect on protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. Ref.5
Mutagenesis1121K → E: Significant reduction of protein expression levels. Significantly reduces prostaglandin D synthase and moderately reduces glutathione-conjugating activities. Ref.5
Mutagenesis1521Y → F: Significant reduction of protein expression levels. Moderately reduces prostaglandin D synthase activity. Ref.5
Mutagenesis1561C → L: No significant effect on protein expression levels. Abolishes prostaglandin D synthase and significantly reduces glutathione-conjugating activities. Ref.5
Mutagenesis1561C → Y: Significant reduction of protein expression levels. Abolishes prostaglandin D synthase and significantly reduces glutathione-conjugating activities. Ref.5
Mutagenesis1981K → E: Moderate reduction of protein expression levels. No significant effect on catalytic activities. Ref.5
Mutagenesis1991L → F: Moderate reduction of protein expression levels. No significant effect on catalytic activities. Ref.5
Sequence conflict1941R → S in AAB72099. Ref.4

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
O35543 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E5EF934D89DC240F

FASTA19923,297
        10         20         30         40         50         60 
MPNYKLLYFN MRGRAEIIRY IFAYLDIKYE DHRIEQADWP KIKPTLPFGK IPVLEVEGLT 

        70         80         90        100        110        120 
LHQSLAIARY LTKNTDLAGK TELEQCQVDA VVDTLDDFMS LFPWAEENQD LKERTFNDLL 

       130        140        150        160        170        180 
TRQAPHLLKD LDTYLGDKEW FIGNYVTWAD FYWDICSTTL LVLKPDLLGI YPRLVSLRNK 

       190 
VQAIPAISAW ILKRPQTKL 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and crystal structure of hematopoietic prostaglandin D synthase."
Kanaoka Y., Ago H., Inagaki E., Nanayama T., Miyano M., Kikuno R., Fujii Y., Eguchi N., Toh H., Urade Y., Hayaishi O.
Cell 90:1085-1095(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, TISSUE SPECIFICITY.
Strain: Sprague-Dawley.
Tissue: Spleen.
[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: Spleen.
[3]"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: Ovary.
[4]"Purification and cloning of rat glutathione-dependent prostaglandin D synthase."
Yuan Y., Reddy R.G., Kim H.
Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 39-198.
Strain: Sprague-Dawley.
Tissue: Spleen.
[5]"Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis."
Pinzar E., Miyano M., Kanaoka Y., Urade Y., Hayaishi O.
J. Biol. Chem. 275:31239-31244(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-8; ARG-14; TRP-104; LYS-112; TYR-152; CYS-156; LYS-198 AND LEU-199.
[6]"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: FUNCTION, CATALYTIC ACTIVITY.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D82071 mRNA. Translation: BAA22898.1.
BC087590 mRNA. Translation: AAH87590.1.
AF021882 mRNA. Translation: AAB72099.1. Frameshift.
RefSeqNP_113832.1. NM_031644.2.
UniGeneRn.10837.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1PD2X-ray2.301/21-199[»]
ProteinModelPortalO35543.
SMRO35543. Positions 1-199.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PRIDEO35543.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000008826; ENSRNOP00000008826; ENSRNOG00000006583.
GeneID58962.
KEGGrno:58962.
UCSCRGD:69251. rat.

Organism-specific databases

CTD27306.
RGD69251. Hpgds.

Phylogenomic databases

eggNOGNOG122057.
GeneTreeENSGT00670000097856.
HOGENOMHOG000115733.
HOVERGENHBG105321.
InParanoidO35543.
KOK01830.
OMAAIAAWIQ.
OrthoDBEOG78WKT1.
PhylomeDBO35543.
TreeFamTF105321.

Enzyme and pathway databases

SABIO-RKO35543.

Gene expression databases

GenevestigatorO35543.

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

EvolutionaryTraceO35543.
NextBio611604.
PROO35543.

Entry information

Entry nameHPGDS_RAT
AccessionPrimary (citable) accession number: O35543
Secondary accession number(s): O35351
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 122 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references