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Protein

Hematopoietic prostaglandin D synthase

Gene

HPGDS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.8 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.7 Publications
RX + glutathione = HX + R-S-glutathione.3 Publications

Cofactori

glutathione4 PublicationsNote: Glutathione is required for the prostaglandin D synthase activity.4 Publications

Activity regulationi

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.1 Publication

Kineticsi

  1. KM=8 mM for glutathione for the glutathione-conjugating activity3 Publications
  2. KM=0.6 mM for glutathione for the prostaglandin D synthase activity in the presence of EDTA3 Publications
  3. KM=0.14 mM for glutathione for the prostaglandin D synthase activity in the presence of magnesium ions3 Publications
  1. Vmax=8.6 µmol/min/mg enzyme with 1-bromo-2,4-dinitrobenzene as substrate3 Publications
  2. Vmax=5.1 µmol/min/mg enzyme with 1-chloro-2,4-dinitrobenzene as substrate3 Publications
  3. Vmax=44.3 µmol/min/mg enzyme with 1-fluoro-2,4-dinitrobenzene as substrate3 Publications
  4. Vmax=10.7 µmol/min/mg enzyme with 1-iodo-2,4-dinitrobenzene as substrate3 Publications
  5. Vmax=6.8 µmol/min/mg enzyme with allyl isothiocyanate as substrate3 Publications
  6. Vmax=6.3 µmol/min/mg enzyme with benzyl isothiocyanate as substrate3 Publications
  7. Vmax=0.05 µmol/min/mg enzyme with cumene hydroperoxide as substrate3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei8Glutathione5 Publications1
Binding sitei14Glutathione5 Publications1
Binding sitei39Glutathione5 Publications1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • glutathione transferase activity Source: Reactome
  • magnesium ion binding Source: UniProtKB
  • prostaglandin-D synthase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionIsomerase, Transferase
Biological processFatty acid biosynthesis, Fatty acid metabolism, Lipid biosynthesis, Lipid metabolism, Prostaglandin biosynthesis, Prostaglandin metabolism
LigandCalcium, Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08788-MONOMER
BRENDAi2.5.1.18 2681
5.3.99.2 2681
ReactomeiR-HSA-156590 Glutathione conjugation
R-HSA-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
SABIO-RKiO60760

Chemistry databases

SwissLipidsiSLP:000000828

Names & Taxonomyi

Protein namesi
Recommended name:
Hematopoietic prostaglandin D synthase (EC:5.3.99.27 Publications)
Short name:
H-PGDS
Alternative name(s):
GST class-sigma
Glutathione S-transferase (EC:2.5.1.183 Publications)
Glutathione-dependent PGD synthase
Glutathione-requiring prostaglandin D synthase
Prostaglandin-H2 D-isomerase
Gene namesi
Name:HPGDS
Synonyms:GSTS, PGDS, PTGDS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000163106.10
HGNCiHGNC:17890 HPGDS
MIMi602598 gene
neXtProtiNX_O60760

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi93D → N: Loss of activation by calcium or magnesium ions. 1 Publication1
Mutagenesisi96D → N: Increases PGD2 synthesis. Loss of activation by calcium or magnesium ions. 1 Publication1
Mutagenesisi97D → N: Reduces PGD2 synthesis by 99%. Loss of activation by calcium or magnesium ions. 1 Publication1

Organism-specific databases

DisGeNETi27306
OpenTargetsiENSG00000163106
PharmGKBiPA165664133

Chemistry databases

ChEMBLiCHEMBL5879
DrugBankiDB08790 1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC ACID
DB01897 2-(2f-Benzothiazolyl)-5-Styryl-3-(4f-Phthalhydrazidyl)Tetrazolium Chloride
DB08695 3-(4-nitrophenyl)-1H-pyrazole
DB07613 3-phenyl-5-(1H-pyrazol-3-yl)isoxazole
DB07917 4-(BENZHYDRYLOXY)-1-[3-(1H-TETRAAZOL-5-YL)PROPYL]PIPERIDINE
DB00143 Glutathione
DB04077 Glycerol
DB08313 nocodazole
DB07615 Tranilast
GuidetoPHARMACOLOGYi1381

Polymorphism and mutation databases

BioMutaiHPGDS

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001859341 – 199Hematopoietic prostaglandin D synthaseAdd BLAST199

Proteomic databases

PaxDbiO60760
PeptideAtlasiO60760
PRIDEiO60760
ProteomicsDBi49588

PTM databases

PhosphoSitePlusiO60760

Expressioni

Tissue specificityi

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.4 Publications

Developmental stagei

Highest levels in immature megakaryocytic cells. Disappears after final differentiation to platelets.1 Publication

Inductioni

By 12-O-tetradecanoylphorbol-13-acetate (TPA).1 Publication

Gene expression databases

BgeeiENSG00000163106 Expressed in 168 organ(s), highest expression level in placenta
GenevisibleiO60760 HS

Organism-specific databases

HPAiHPA024035

Interactioni

Subunit structurei

Homodimer.5 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118128, 4 interactors
IntActiO60760, 7 interactors
STRINGi9606.ENSP00000295256

Chemistry databases

BindingDBiO60760

Structurei

Secondary structure

1199
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO60760
SMRiO60760
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO60760

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 79GST N-terminalAdd BLAST78
Domaini81 – 199GST C-terminalAdd BLAST119

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni49 – 51Glutathione binding5 Publications3
Regioni63 – 64Glutathione binding5 Publications2

Sequence similaritiesi

Belongs to the GST superfamily. Sigma family.Curated

Phylogenomic databases

eggNOGiKOG1695 Eukaryota
ENOG4111VAU LUCA
GeneTreeiENSGT00670000097856
HOGENOMiHOG000115733
HOVERGENiHBG105321
InParanoidiO60760
KOiK04097
OMAiTEMEQCH
OrthoDBiEOG091G0MBB
PhylomeDBiO60760
TreeFamiTF105321

Family and domain databases

InterProiView protein in InterPro
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR040079 Glutathione_S-Trfase
IPR004045 Glutathione_S-Trfase_N
IPR004046 GST_C
IPR036249 Thioredoxin-like_sf
PfamiView protein in Pfam
PF14497 GST_C_3, 1 hit
PF02798 GST_N, 1 hit
SFLDiSFLDS00019 Glutathione_Transferase_(cytos, 1 hit
SUPFAMiSSF47616 SSF47616, 1 hit
SSF52833 SSF52833, 1 hit
PROSITEiView protein in PROSITE
PS50405 GST_CTER, 1 hit
PS50404 GST_NTER, 1 hit

Sequencei

Sequence statusi: Complete.

O60760-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPNYKLTYFN MRGRAEIIRY IFAYLDIQYE DHRIEQADWP EIKSTLPFGK
60 70 80 90 100
IPILEVDGLT LHQSLAIARY LTKNTDLAGN TEMEQCHVDA IVDTLDDFMS
110 120 130 140 150
CFPWAEKKQD VKEQMFNELL TYNAPHLMQD LDTYLGGREW LIGNSVTWAD
160 170 180 190
FYWEICSTTL LVFKPDLLDN HPRLVTLRKK VQAIPAVANW IKRRPQTKL
Length:199
Mass (Da):23,344
Last modified:January 23, 2007 - v3
Checksum:iA4ED2476B16CC5C3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti187V → I no nucleotide entry (PubMed:11672424).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS3640.1
RefSeqiNP_055300.1, NM_014485.2
UniGeneiHs.128433

Genome annotation databases

EnsembliENST00000295256; ENSP00000295256; ENSG00000163106
GeneIDi27306
KEGGihsa:27306
UCSCiuc003hte.2 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS3640.1
RefSeqiNP_055300.1, NM_014485.2
UniGeneiHs.128433

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5AISX-ray1.85A/B/C/D2-199[»]
5AIVX-ray2.04A/B/C/D2-199[»]
5AIXX-ray2.10A/B/C/D2-199[»]
5YWXX-ray1.74A/B/C/D2-199[»]
ProteinModelPortaliO60760
SMRiO60760
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118128, 4 interactors
IntActiO60760, 7 interactors
STRINGi9606.ENSP00000295256

Chemistry databases

BindingDBiO60760
ChEMBLiCHEMBL5879
DrugBankiDB08790 1-PHENYL-1H-PYRAZOLE-4-CARBOXYLIC ACID
DB01897 2-(2f-Benzothiazolyl)-5-Styryl-3-(4f-Phthalhydrazidyl)Tetrazolium Chloride
DB08695 3-(4-nitrophenyl)-1H-pyrazole
DB07613 3-phenyl-5-(1H-pyrazol-3-yl)isoxazole
DB07917 4-(BENZHYDRYLOXY)-1-[3-(1H-TETRAAZOL-5-YL)PROPYL]PIPERIDINE
DB00143 Glutathione
DB04077 Glycerol
DB08313 nocodazole
DB07615 Tranilast
GuidetoPHARMACOLOGYi1381
SwissLipidsiSLP:000000828

PTM databases

PhosphoSitePlusiO60760

Polymorphism and mutation databases

BioMutaiHPGDS

Proteomic databases

PaxDbiO60760
PeptideAtlasiO60760
PRIDEiO60760
ProteomicsDBi49588

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295256; ENSP00000295256; ENSG00000163106
GeneIDi27306
KEGGihsa:27306
UCSCiuc003hte.2 human

Organism-specific databases

CTDi27306
DisGeNETi27306
EuPathDBiHostDB:ENSG00000163106.10
GeneCardsiHPGDS
HGNCiHGNC:17890 HPGDS
HPAiHPA024035
MIMi602598 gene
neXtProtiNX_O60760
OpenTargetsiENSG00000163106
PharmGKBiPA165664133
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1695 Eukaryota
ENOG4111VAU LUCA
GeneTreeiENSGT00670000097856
HOGENOMiHOG000115733
HOVERGENiHBG105321
InParanoidiO60760
KOiK04097
OMAiTEMEQCH
OrthoDBiEOG091G0MBB
PhylomeDBiO60760
TreeFamiTF105321

Enzyme and pathway databases

BioCyciMetaCyc:HS08788-MONOMER
BRENDAi2.5.1.18 2681
5.3.99.2 2681
ReactomeiR-HSA-156590 Glutathione conjugation
R-HSA-2162123 Synthesis of Prostaglandins (PG) and Thromboxanes (TX)
SABIO-RKiO60760

Miscellaneous databases

EvolutionaryTraceiO60760
GeneWikiiPGDS
GenomeRNAii27306
PROiPR:O60760
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163106 Expressed in 168 organ(s), highest expression level in placenta
GenevisibleiO60760 HS

Family and domain databases

InterProiView protein in InterPro
IPR010987 Glutathione-S-Trfase_C-like
IPR036282 Glutathione-S-Trfase_C_sf
IPR040079 Glutathione_S-Trfase
IPR004045 Glutathione_S-Trfase_N
IPR004046 GST_C
IPR036249 Thioredoxin-like_sf
PfamiView protein in Pfam
PF14497 GST_C_3, 1 hit
PF02798 GST_N, 1 hit
SFLDiSFLDS00019 Glutathione_Transferase_(cytos, 1 hit
SUPFAMiSSF47616 SSF47616, 1 hit
SSF52833 SSF52833, 1 hit
PROSITEiView protein in PROSITE
PS50405 GST_CTER, 1 hit
PS50404 GST_NTER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHPGDS_HUMAN
AccessioniPrimary (citable) accession number: O60760
Secondary accession number(s): Q6FHT9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 170 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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