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Protein

Hematopoietic prostaglandin D synthase

Gene

HPGDS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.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

Enzyme 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

  • cyclooxygenase pathway Source: Reactome
  • glutathione derivative biosynthetic process Source: Reactome
  • locomotory behavior Source: ProtInc
  • negative regulation of male germ cell proliferation Source: Ensembl
  • prostaglandin metabolic process Source: UniProtKB
  • signal transduction Source: ProtInc
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

Keywords - Ligandi

Calcium, Magnesium, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08788-MONOMER.
ZFISH: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-RKO60760.

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

HGNCiHGNC:17890. HPGDS.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: ProtInc
  • cytosol Source: Reactome
Complete GO annotation...

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.
DrugBankiDB00143. Glutathione.
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.

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.
GenevisibleiO60760. HS.

Organism-specific databases

HPAiHPA024035.

Interactioni

Subunit structurei

Homodimer.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ABHD17AQ96GS63EBI-10187349,EBI-2870273
ARRDC3Q96B673EBI-10187349,EBI-2875665
MELTFP08582-23EBI-10187349,EBI-10195914

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi118128. 4 interactors.
IntActiO60760. 5 interactors.
STRINGi9606.ENSP00000295256.

Chemistry databases

BindingDBiO60760.

Structurei

Secondary structure

1199
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 12Combined sources9
Helixi13 – 15Combined sources3
Helixi16 – 24Combined sources9
Beta strandi30 – 34Combined sources5
Helixi36 – 38Combined sources3
Helixi39 – 43Combined sources5
Beta strandi46 – 49Combined sources4
Beta strandi53 – 56Combined sources4
Beta strandi59 – 62Combined sources4
Helixi64 – 72Combined sources9
Helixi76 – 78Combined sources3
Helixi82 – 100Combined sources19
Helixi109 – 121Combined sources13
Helixi123 – 135Combined sources13
Beta strandi139 – 142Combined sources4
Helixi148 – 163Combined sources16
Turni165 – 170Combined sources6
Helixi172 – 182Combined sources11
Helixi185 – 193Combined sources9

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[»]
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
Contains 1 GST C-terminal domain.Curated
Contains 1 GST N-terminal domain.Curated

Phylogenomic databases

eggNOGiKOG1695. Eukaryota.
ENOG4111VAU. LUCA.
GeneTreeiENSGT00670000097856.
HOGENOMiHOG000115733.
HOVERGENiHBG105321.
InParanoidiO60760.
KOiK04097.
OMAiYLGENEW.
OrthoDBiEOG091G0MBB.
PhylomeDBiO60760.
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]
PfamiPF14497. GST_C_3. 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.

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.

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[»]
ProteinModelPortaliO60760.
SMRiO60760.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118128. 4 interactors.
IntActiO60760. 5 interactors.
STRINGi9606.ENSP00000295256.

Chemistry databases

BindingDBiO60760.
ChEMBLiCHEMBL5879.
DrugBankiDB00143. Glutathione.
DB07615. Tranilast.
GuidetoPHARMACOLOGYi1381.
SwissLipidsiSLP:000000828.

PTM databases

PhosphoSitePlusiO60760.

Polymorphism and mutation databases

BioMutaiHPGDS.

Proteomic databases

PaxDbiO60760.
PeptideAtlasiO60760.
PRIDEiO60760.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

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

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciMetaCyc:HS08788-MONOMER.
ZFISH: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-RKO60760.

Miscellaneous databases

EvolutionaryTraceiO60760.
GeneWikiiPGDS.
GenomeRNAii27306.
PROiO60760.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163106.
GenevisibleiO60760. HS.

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]
PfamiPF14497. GST_C_3. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiHPGDS_HUMAN
AccessioniPrimary (citable) accession number: O60760
Secondary accession number(s): Q6FHT9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 160 of the entry and version 3 of the sequence. [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. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.