GO:0004667 prostaglandin-D synthase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0004667 (prostaglandin-D synthase activity) is a molecular_function term defined as catalysis of the reaction prostaglandin H2 = prostaglandin D2 [QuickGO].
• The reaction is an isomerization that converts the unstable endoperoxide PGH2 into PGD2, a key prostanoid mediator.
• Enzymes annotated with this activity include hematopoietic prostaglandin D synthase (HPGDS/PTGDS) and some glutathione transferases [1,5].
• PGD2 signaling is implicated in allergic inflammation, tumor immune evasion, diabetic nephropathy, and Duchenne muscular dystrophy [2,4,6,8].
• PTGDS has been linked to diffuse large B-cell lymphoma tumorigenesis through MYH9-mediated Wnt-beta-catenin-STAT3 signaling.
• CRISPR knockout, point-mutation, knock-in, and overexpression models enable causal dissection of PGD2 synthase function in disease [2,4,7].
Description
Prostaglandin-D synthase activity (GO:0004667) is a molecular function that catalyzes the isomerization of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2) [QuickGO]. This activity is central to the biosynthesis of PGD2, a lipid mediator involved in allergic responses, immune regulation, and tissue homeostasis. Enzymes with this activity, such as hematopoietic prostaglandin D synthase (HPGDS), have been studied in parasitic trematodes, allergic inflammation, and tumor immunology [1,2,6]. Understanding GO:0004667 is important because PGD2 and its synthases influence diverse pathological processes, including cancer, nephropathy, and muscular dystrophy [4,7,8]. Researchers use this term to annotate gene products that directly catalyze PGD2 formation, distinguishing them from other prostanoid synthases [QuickGO]. The availability of CRISPR-based models now allows precise interrogation of genes encoding this activity in human disease contexts [2,4,7].
prostaglandin-D synthase activity At A Glance
| GO ID | GO:0004667 |
|---|---|
| GO term | prostaglandin-D synthase activity |
| Ontology | molecular_function |
| Synonym | PGD2 synthase activity; PGH-PGD isomerase activity; prostaglandin-H2 D-isomerase activity; prostaglandin D2 synthase activity |
| Definition | Catalysis of the reaction: prostaglandin H(2) = prostaglandin D(2). |
| Major function | Isomerization of PGH2 to PGD2, a key prostanoid mediator. |
| Representative enzymes | Hematopoietic prostaglandin D synthase (HPGDS/PTGDS); some glutathione transferases [1,5]. |
| Related diseases | Allergic inflammation, diffuse large B-cell lymphoma, diabetic nephropathy, Duchenne muscular dystrophy [4,6,7,8]. |
What Is GO:0004667?
In our own words, GO:0004667 describes the enzymatic activity that converts prostaglandin H2 (PGH2) into prostaglandin D2 (PGD2) [QuickGO]. This is an isomerization reaction, meaning the substrate's molecular formula is rearranged without adding or removing atoms. The activity is classified under molecular_function and is synonymous with PGD2 synthase activity, PGH-PGD isomerase activity, and prostaglandin-H2 D-isomerase activity [QuickGO]. It is distinct from other prostanoid synthase activities that produce prostaglandin E2, F2alpha, or thromboxane A2 [QuickGO].
Why Is prostaglandin-D synthase activity Important in Cell Biology?
GO:0004667 is important because it defines the enzymatic step that produces PGD2, a lipid mediator with broad roles in allergy, immunity, and cancer. Dysregulation of PGD2 synthase activity has been linked to exacerbated diabetic nephropathy in periodontitis, tumor immune evasion, and muscular dystrophy pathology [2,4,8]. Targeting this activity with degraders or inhibitors is an active therapeutic strategy. Thus, precise annotation and experimental modeling of GO:0004667 are essential for understanding and manipulating PGD2-driven biology [1,5].
• Defines the biosynthetic route to PGD2, a major prostanoid.
• Enables annotation of HPGDS/PTGDS and related glutathione transferases [1,5].
• Links to allergic inflammation and mast cell biology [6,8].
• Implicated in tumor immunosuppression and macrophage reeducation.
• Associated with diabetic nephropathy exacerbation by periodontitis.
• Relevant to Duchenne muscular dystrophy myocardial pathology.
• Provides a target for degradation inducers and small-molecule modulators.
• Supports CRISPR-based causal studies of PGD2 synthase genes [2,4,7].
• Helps distinguish PGD2 synthesis from other prostanoid pathways [QuickGO].
• Facilitates cross-species studies, including parasitic trematodes.
Mechanism, Genes and Research Methods
Substrate binding and isomerization
In simple terms: The enzyme grabs PGH2 and rearranges it into PGD2.
Prostaglandin-D synthase activity catalyzes the isomerization of prostaglandin H2 (PGH2) to prostaglandin D2 (PGD2) [QuickGO]. This reaction is a rearrangement of the endoperoxide substrate without net addition or removal of atoms. In parasitic trematodes, sigma- and mu-class glutathione transferases exhibit prostaglandin synthase activity, demonstrating evolutionary diversity in this function.
Enzyme families and structural context
In simple terms: Different proteins can perform this reaction, including HPGDS and some glutathione transferases.
Hematopoietic prostaglandin D synthase (HPGDS) is a well-characterized enzyme with this activity, and its degradation has been explored as a therapeutic approach. Glutathione transferases from Clonorchis sinensis also display prostaglandin synthase activity, indicating that GO:0004667 can be carried out by multiple protein folds. The activity is distinct from other prostanoid synthases, as defined by the GO term [QuickGO].
Cellular roles of PGD2 produced by this activity
In simple terms: PGD2 made by this enzyme acts as a signal in immune and tissue responses.
PGD2 produced via this activity influences allergic inflammation and mast cell biology [6,8]. In tumor immunology, PGD2 signaling contributes to macrophage-mediated immunosuppression, and activated T cells can break this suppression by reeducating macrophages. In diabetic nephropathy, the glomerular HPGDS-PGD2 axis exacerbates injury in periodontitis-related models.
Regulation and therapeutic targeting
In simple terms: The activity can be turned up or down, and drugs can target the enzyme.
HPGDS expression is increased in mast cells and pericytes in Duchenne muscular dystrophy myocardial specimens, suggesting disease-associated regulation. A hematopoietic prostaglandin D synthase-degradation inducer has been developed, showing that this activity can be pharmacologically modulated. PTGDS promotes diffuse large B-cell lymphoma tumorigenesis via MYH9-mediated Wnt-beta-catenin-STAT3 signaling, linking this activity to oncogenic pathways.
Key Genes Involved in GO:0004667 prostaglandin-D synthase activity
The following genes and proteins are directly or indirectly associated with prostaglandin-D synthase activity (GO:0004667) based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| HPGDS (PTGDS) | Hematopoietic prostaglandin D synthase; catalyzes PGH2 to PGD2 | Target for degradation inducers; implicated in allergic inflammation and DMD [5,6,8] |
| PTGDS | Lipocalin-type prostaglandin D synthase; also exhibits this activity | Promotes DLBCL tumorigenesis via MYH9/Wnt/STAT3 |
| GSTA1/GSTA2 | Glutathione transferases with prostaglandin synthase activity in trematodes | Evolutionary and parasitic studies |
| GSTM1/GSTM2 | Mu-class glutathione transferases with prostaglandin synthase activity | Parasite biology and detoxification |
| MYH9 | Non-muscle myosin heavy chain; mediates PTGDS signaling | DLBCL tumorigenesis |
| CTNNB1 | Beta-catenin; downstream of PTGDS in Wnt signaling | DLBCL and cancer pathways |
| STAT3 | Signal transducer and activator of transcription 3; downstream of PTGDS | DLBCL and inflammation |
| PTGS1/COX1 | Upstream enzyme producing PGH2 | Prostanoid biosynthesis [QuickGO] |
| PTGS2/COX2 | Upstream enzyme producing PGH2 | Inflammation and cancer [QuickGO] |
| TBXAS1 | Thromboxane A synthase; related prostanoid pathway | Distinct from PGD2 synthesis [QuickGO] |
| PTGES | Prostaglandin E synthase; related pathway | Distinct from PGD2 synthesis [QuickGO] |
| HPGD | 15-hydroxyprostaglandin dehydrogenase; degrades PGD2 | Catabolism of PGD2 [QuickGO] |
| SLCO2A1 | Prostaglandin transporter | PGD2 transport [QuickGO] |
| PTGFR | PGD2 receptor (DP1) | PGD2 signaling [QuickGO] |
| CRTH2 (PTGDR2) | PGD2 receptor (DP2) | Allergic inflammation |
| MAST cells markers | Mast cells express HPGDS | Allergic inflammation and DMD [6,8] |
| Macrophages | PGD2-mediated immunosuppression | Tumor immunology |
How Is prostaglandin-D synthase activity Regulated?
Prostaglandin-D synthase activity is regulated at multiple levels. HPGDS expression is increased in mast cells and pericytes in Duchenne muscular dystrophy myocardial specimens, indicating disease-associated upregulation. A degradation inducer has been developed to reduce HPGDS levels, showing that protein stability can be pharmacologically controlled. In periodontitis-related diabetic nephropathy, the glomerular HPGDS-PGD2 axis is exacerbated, suggesting inflammatory regulation. PTGDS promotes DLBCL tumorigenesis through MYH9-mediated Wnt-beta-catenin-STAT3 signaling, linking this activity to oncogenic transcriptional programs.
prostaglandin-D synthase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HPGDS (PTGDS) | Allergic inflammation | Knockout mouse, mast cell-specific deletion |
| PTGDS | Diffuse large B-cell lymphoma | Knockout or overexpression in DLBCL cell lines |
| HPGDS | Diabetic nephropathy with periodontitis | KK-A(y) mice with periodontitis |
| HPGDS | Duchenne muscular dystrophy myocardial pathology | Human autopsy specimens, mouse models |
| Glutathione transferases | Parasitic trematode infection | Clonorchis sinensis models |
Allergic inflammation and mast cell disorders
HPGDS and PGD2 are key mediators in allergic inflammation, and therapeutic potential of hematopoietic prostaglandin D2 synthase has been reviewed. HPGDS is increased in mast cells in Duchenne muscular dystrophy myocardial specimens, linking this activity to mast cell-driven pathology.
Cancer and tumor immunosuppression
Activated T cells can break tumor immunosuppression by macrophage reeducation, a process involving PGD2 signaling. PTGDS promotes diffuse large B-cell lymphoma tumorigenesis via MYH9-mediated regulation of Wnt-beta-catenin-STAT3 signaling.
Diabetic nephropathy and periodontitis
The glomerular hematopoietic prostaglandin D synthase-PGD2 axis contributes to periodontitis-related exacerbation of diabetic nephropathy in KK-A(y) mice.
Muscular dystrophy
Hematopoietic prostaglandin D synthase is increased in mast cells and pericytes in autopsy myocardial specimens from patients with Duchenne muscular dystrophy.
From prostaglandin-D synthase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of HPGDS reduce allergic inflammation? | HPGDS knockout mouse |
| Can PTGDS drive DLBCL tumorigenesis? | PTGDS overexpression in DLBCL cell lines |
| Does HPGDS degradation ameliorate disease? | HPGDS degradation inducer in disease models |
| Is the HPGDS-PGD2 axis required for diabetic nephropathy exacerbation? | Kidney-specific knockout in KK-A(y) mice |
| What is the role of PGD2 in tumor immunosuppression? | Macrophage-specific knockout or overexpression |
| Do parasitic glutathione transferases contribute to PGD2 synthesis? | Knockout in Clonorchis sinensis |
How to Study the prostaglandin-D synthase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| LC-MS/MS | PGD2 production from PGH2 | Enzyme activity assays |
| qRT-PCR | HPGDS/PTGDS mRNA levels | Expression profiling [7,8] |
| Immunohistochemistry | Protein localization | Tissue studies |
| Western blot | Protein abundance | Cell line validation |
| CRISPR knockout | Loss-of-function effects | Causal gene studies [2,4] |
| CRISPR knock-in | Tagged or mutant alleles | Tracking and mutation studies |
| Overexpression | Gain-of-function effects | Tumorigenesis assays |
| Flow cytometry | Immune cell populations | Macrophage reeducation |
Enzymatic activity assays
Prostaglandin-D synthase activity can be measured by monitoring the conversion of PGH2 to PGD2 using mass spectrometry or spectrophotometric methods [1,5].
Expression analysis
RNA-seq and qPCR can quantify HPGDS/PTGDS transcript levels in tissues and cell models, as shown in DMD myocardial specimens and DLBCL studies [7,8].
Proteomics and immunohistochemistry
Protein expression and localization of HPGDS can be assessed by immunohistochemistry and proteomics, as demonstrated in mast cells and pericytes in DMD.
CRISPR-based perturbation
CRISPR knockout, knock-in, and overexpression models enable causal testing of genes encoding this activity in disease contexts [2,4,7].
How CRISPR Can Be Used to Study GO:0004667 prostaglandin-D synthase activity
Knockout
CRISPR knockout of HPGDS or PTGDS can abolish prostaglandin-D synthase activity, enabling studies of PGD2-dependent phenotypes in allergy, cancer, and nephropathy [2,4,6].
Point Mutation
Point mutations can be introduced into the catalytic site of HPGDS to dissect residues required for isomerization of PGH2 to PGD2 [1,5].
Knock-in
Knock-in of epitope tags or fluorescent reporters allows tracking of HPGDS expression and localization in vivo, as relevant to mast cell and pericyte studies.
Overexpression
Overexpression of PTGDS in DLBCL cell lines can drive tumorigenesis via MYH9-mediated Wnt-beta-catenin-STAT3 signaling, providing a gain-of-function model.
How EDITGENE Supports prostaglandin-D synthase activity Research
Researchers studying prostaglandin-D synthase activity-related genes often need to determine whether a candidate gene is causally involved in PGD2 production and disease phenotypes. EDITGENE provides CRISPR-based services to generate precisely engineered cell and animal models for such studies.
Contact EDITGENE today to design your custom CRISPR model for prostaglandin-D synthase activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PTGES Knockout HEK293 Cell Line | EDJ-KQ3248 | Human | 9536 | Details Get a Quote |
| PTGDS Knockout HEK293 Cell Line | EDJ-KQ5581 | Human | 5730 | Details Get a Quote |
| HPGDS Knockout HEK293 Cell Line | EDJ-KQ8757 | Human | 27306 | Details Get a Quote |
| PTGES Knockout A-549 Cell Line | EDJ-KQ24779 | Human | 9536 | Details Get a Quote |
| PTGES Knockout HCT 116 Cell Line | EDJ-KQ24780 | Human | 9536 | Details Get a Quote |
| PTGES Knockout HeLa Cell Line | EDJ-KQ24781 | Human | 9536 | Details Get a Quote |
| PTGDS Knockout HeLa Cell Line | EDJ-KQ54255 | Human | 5730 | Details Get a Quote |
| HPGDS Knockout HeLa Cell Line | EDJ-KQ56055 | Human | 27306 | Details Get a Quote |
| PTGDS Knockout A-549 Cell Line | EDJ-KQ62746 | Human | 5730 | Details Get a Quote |
| HPGDS Knockout A-549 Cell Line | EDJ-KQ64539 | Human | 27306 | Details Get a Quote |
| PTGDS Knockout HCT 116 Cell Line | EDJ-KQ71215 | Human | 5730 | Details Get a Quote |
| HPGDS Knockout HCT 116 Cell Line | EDJ-KQ72998 | Human | 27306 | Details Get a Quote |
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Frequently Asked Questions About prostaglandin-D synthase activity
What is prostaglandin-D synthase activity?
It is the enzymatic activity that catalyzes the conversion of prostaglandin H2 to prostaglandin D2, defined by GO:0004667 [QuickGO].
What genes are involved in prostaglandin-D synthase activity?
HPGDS (PTGDS) and some glutathione transferases, such as those from Clonorchis sinensis, exhibit this activity [1,5].
What is the GO ID for prostaglandin-D synthase activity?
The GO ID is GO:0004667 [QuickGO].
Which diseases are linked to prostaglandin-D synthase activity?
Allergic inflammation, diffuse large B-cell lymphoma, diabetic nephropathy, and Duchenne muscular dystrophy have been linked [4,6,7,8].
How is prostaglandin-D synthase activity regulated?
It is regulated by expression changes, protein stability, and inflammatory signals, as shown in DMD and periodontitis models [4,5,8].
What is the substrate of prostaglandin-D synthase?
The substrate is prostaglandin H2 (PGH2) [QuickGO].
What is the product of prostaglandin-D synthase activity?
The product is prostaglandin D2 (PGD2) [QuickGO].
Can CRISPR be used to study prostaglandin-D synthase activity?
Yes, CRISPR knockout, knock-in, and overexpression models enable causal studies of genes encoding this activity [2,4,7].
What cell types express hematopoietic prostaglandin D synthase?
Mast cells and pericytes express HPGDS, as shown in DMD myocardial specimens.
Is there a therapeutic targeting prostaglandin-D synthase?
A hematopoietic prostaglandin D synthase-degradation inducer has been developed, showing therapeutic potential.
Conclusion
Prostaglandin-D synthase activity (GO:0004667) is a molecular function that produces PGD2, a lipid mediator with critical roles in allergy, cancer, and tissue injury [1,6]. Its representative enzymes, HPGDS and PTGDS, are implicated in diverse diseases including DLBCL, diabetic nephropathy, and Duchenne muscular dystrophy [4,7,8]. CRISPR-based models provide powerful tools to dissect the causal roles of these genes and to evaluate therapeutic strategies targeting this activity [2,5].
References
- 1. Kim J et al.. 2024. Prostaglandin synthase activity of sigma- and mu-class glutathione transferases in a parasitic trematode, Clonorchis sinensis.. Parasites Hosts Dis 62(2):205-216 PMID: 38835261
- 2. Trotta R et al.. 2025. Activated T Cells Break Tumor Immunosuppression by Macrophage Reeducation.. Cancer Discov 15(7):1410-1436 PMID: 40094380
- 4. Sato K et al.. 2025. Glomerular Haematopoietic Prostaglandin D Synthase-Prostaglandin D2 Axis Contributes to the Periodontitis-Related Exacerbation of Diabetic Nephropathy in KK-A(y) Mice.. J Clin Periodontol 52(8):1211-1220 PMID: 40524609
- 5. Yokoo H et al.. 2021. Development of a Hematopoietic Prostaglandin D Synthase-Degradation Inducer.. ACS Med Chem Lett 12(2):236-241 PMID: 33603969
- 6. Rittchen S et al.. 2019. Therapeutic Potential of Hematopoietic Prostaglandin D(2) Synthase in Allergic Inflammation.. Cells 8(6) PMID: 31226822
- 7. Hu S et al.. 2022. Glycoprotein PTGDS promotes tumorigenesis of diffuse large B-cell lymphoma by MYH9-mediated regulation of Wnt-β-catenin-STAT3 signaling.. Cell Death Differ 29(3):642-656 PMID: 34743203
- 8. Hamamura K et al.. 2024. Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy.. Int J Mol Sci 25(3) PMID: 38339125
