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O35543

- HPGDS_RAT

UniProt

O35543 - HPGDS_RAT

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Protein
Hematopoietic prostaglandin D synthase
Gene
Hpgds, Gsts, Pgds, Ptgds2
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

(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.4 Publications
RX + glutathione = HX + R-S-glutathione.4 Publications

Cofactori

Glutathione. Required for the prostaglandin D synthase activity.2 Publications

Kineticsi

  1. KM=100 µM for glutathione for the prostaglandin D synthase activity2 Publications
  2. KM=500 µM for glutathione for the glutathione-conjugating activity
  3. KM=500 µM for PGH2 for the prostaglandin D synthase activity
  4. 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei8 – 81Glutathione
Binding sitei14 – 141Glutathione
Binding sitei39 – 391Glutathione
Binding sitei51 – 511Glutathione; via amide nitrogen and carbonyl oxygen

GO - Molecular functioni

  1. calcium ion binding Source: UniProtKB
  2. glutathione transferase activity Source: UniProtKB-EC
  3. magnesium ion binding Source: UniProtKB
  4. prostaglandin-D synthase activity Source: UniProtKB

GO - Biological processi

  1. prostaglandin biosynthetic process Source: RGD
  2. prostaglandin metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Transferase

Keywords - Biological processi

Fatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism

Enzyme and pathway databases

ReactomeiREACT_194948. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
SABIO-RKO35543.

Names & Taxonomyi

Protein namesi
Recommended name:
Hematopoietic prostaglandin D synthase (EC:5.3.99.2)
Short name:
H-PGDS
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 namesi
Name:Hpgds
Synonyms:Gsts, Pgds, Ptgds2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 4

Organism-specific databases

RGDi69251. Hpgds.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-SubCell
  2. nucleus Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi8 – 81Y → F: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. 1 Publication
Mutagenesisi14 – 141R → E: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. 1 Publication
Mutagenesisi14 – 141R → K: Moderate reduction of protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. 1 Publication
Mutagenesisi104 – 1041W → I: No significant effect on protein expression levels. Abolishes both prostaglandin D synthase and glutathione-conjugating activities. 1 Publication
Mutagenesisi112 – 1121K → E: Significant reduction of protein expression levels. Significantly reduces prostaglandin D synthase and moderately reduces glutathione-conjugating activities. 1 Publication
Mutagenesisi152 – 1521Y → F: Significant reduction of protein expression levels. Moderately reduces prostaglandin D synthase activity. 1 Publication
Mutagenesisi156 – 1561C → L: No significant effect on protein expression levels. Abolishes prostaglandin D synthase and significantly reduces glutathione-conjugating activities. 1 Publication
Mutagenesisi156 – 1561C → Y: Significant reduction of protein expression levels. Abolishes prostaglandin D synthase and significantly reduces glutathione-conjugating activities. 1 Publication
Mutagenesisi198 – 1981K → E: Moderate reduction of protein expression levels. No significant effect on catalytic activities. 1 Publication
Mutagenesisi199 – 1991L → F: Moderate reduction of protein expression levels. No significant effect on catalytic activities. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 199199Hematopoietic prostaglandin D synthase
PRO_0000185936Add
BLAST

Proteomic databases

PRIDEiO35543.

Expressioni

Tissue specificityi

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).2 Publications

Gene expression databases

GenevestigatoriO35543.

Interactioni

Subunit structurei

Homodimer.1 Publication

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 129
Turni13 – 153
Helixi16 – 249
Beta strandi30 – 345
Turni36 – 383
Helixi39 – 424
Helixi43 – 453
Beta strandi53 – 564
Beta strandi59 – 624
Helixi64 – 718
Turni72 – 743
Helixi76 – 783
Helixi82 – 9918
Helixi109 – 12214
Helixi124 – 13512
Beta strandi139 – 1457
Helixi148 – 16316
Turni165 – 1706
Helixi172 – 18312
Helixi185 – 1939

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1PD2X-ray2.301/21-199[»]
ProteinModelPortaliO35543.
SMRiO35543. Positions 1-199.

Miscellaneous databases

EvolutionaryTraceiO35543.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 7978GST N-terminal
Add
BLAST
Domaini81 – 199119GST C-terminal
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni63 – 642Glutathione binding

Sequence similaritiesi

Belongs to the GST superfamily. Sigma family.

Phylogenomic databases

eggNOGiNOG122057.
GeneTreeiENSGT00670000097856.
HOGENOMiHOG000115733.
HOVERGENiHBG105321.
InParanoidiO35543.
KOiK01830.
OMAiNIEMKAN.
OrthoDBiEOG78WKT1.
PhylomeDBiO35543.
TreeFamiTF105321.

Family and domain databases

Gene3Di1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProiIPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PfamiPF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]
SUPFAMiSSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEiPS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O35543-1 [UniParc]FASTAAdd to Basket

« Hide

MPNYKLLYFN MRGRAEIIRY IFAYLDIKYE DHRIEQADWP KIKPTLPFGK    50
IPVLEVEGLT LHQSLAIARY LTKNTDLAGK TELEQCQVDA VVDTLDDFMS 100
LFPWAEENQD LKERTFNDLL TRQAPHLLKD LDTYLGDKEW FIGNYVTWAD 150
FYWDICSTTL LVLKPDLLGI YPRLVSLRNK VQAIPAISAW ILKRPQTKL 199
Length:199
Mass (Da):23,297
Last modified:January 23, 2007 - v3
Checksum:iE5EF934D89DC240F
GO

Sequence cautioni

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti194 – 1941R → S in AAB72099. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D82071 mRNA. Translation: BAA22898.1.
BC087590 mRNA. Translation: AAH87590.1.
AF021882 mRNA. Translation: AAB72099.1. Frameshift.
RefSeqiNP_113832.1. NM_031644.2.
UniGeneiRn.10837.

Genome annotation databases

EnsembliENSRNOT00000008826; ENSRNOP00000008826; ENSRNOG00000006583.
GeneIDi58962.
KEGGirno:58962.
UCSCiRGD:69251. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
D82071 mRNA. Translation: BAA22898.1 .
BC087590 mRNA. Translation: AAH87590.1 .
AF021882 mRNA. Translation: AAB72099.1 . Frameshift.
RefSeqi NP_113832.1. NM_031644.2.
UniGenei Rn.10837.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1PD2 X-ray 2.30 1/2 1-199 [» ]
ProteinModelPortali O35543.
SMRi O35543. Positions 1-199.
ModBasei Search...
MobiDBi Search...

Proteomic databases

PRIDEi O35543.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000008826 ; ENSRNOP00000008826 ; ENSRNOG00000006583 .
GeneIDi 58962.
KEGGi rno:58962.
UCSCi RGD:69251. rat.

Organism-specific databases

CTDi 27306.
RGDi 69251. Hpgds.

Phylogenomic databases

eggNOGi NOG122057.
GeneTreei ENSGT00670000097856.
HOGENOMi HOG000115733.
HOVERGENi HBG105321.
InParanoidi O35543.
KOi K01830.
OMAi NIEMKAN.
OrthoDBi EOG78WKT1.
PhylomeDBi O35543.
TreeFami TF105321.

Enzyme and pathway databases

Reactomei REACT_194948. Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
SABIO-RK O35543.

Miscellaneous databases

EvolutionaryTracei O35543.
NextBioi 611604.
PROi O35543.

Gene expression databases

Genevestigatori O35543.

Family and domain databases

Gene3Di 1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.
InterProi IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR004046. GST_C.
IPR012336. Thioredoxin-like_fold.
[Graphical view ]
Pfami PF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view ]
SUPFAMi SSF47616. SSF47616. 1 hit.
SSF52833. SSF52833. 1 hit.
PROSITEi PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiHPGDS_RAT
AccessioniPrimary (citable) accession number: O35543
Secondary accession number(s): O35351
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 124 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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