Details for: PTGDR2

Gene ID: 11251

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PTGDR2

Ensembl ID: ENSG00000183134

Description: prostaglandin D2 receptor 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • group 2 innate lymphoid cell CL0001069
    CSI 2.56
    rCSI 13.84%
    PRS 99.65
  • stromal cell CL0000499
    CSI 2.13
    rCSI 5.98%
    PRS 99.26

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PTGDR2](/details-gene/11251), or Prostaglandin D2 Receptor 2, encodes a G protein-coupled receptor that functions as a key mediator of inflammatory processes, particularly those associated with type 2 immunity. Also known as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), it binds to prostaglandin D2 (PGD2), a major pro-inflammatory lipid mediator released primarily by mast cells. This interaction triggers intracellular signaling cascades, most notably through G alpha (i) proteins ([R-HSA-418594](https://reactome.org/content/detail/R-HSA-418594)), leading to cellular responses such as [chemotaxis](/details-cell/GO0006935). **Overall** expression data highlights its significant role as a defining marker for [group 2 innate lymphoid cell](/details-cell/CL0001069) (CSI: 2.56), a critical cell type in allergic inflammation, and also shows notable expression in [stromal cell](/details-cell/CL0000499) (CSI: 2.13), suggesting a broader role in tissue-level immune responses. ## Cellular Roles and Expression Landscape The expression profile of [PTGDR2](/details-gene/11251) firmly establishes its role within the immune system, particularly in cells that orchestrate type 2 allergic and inflammatory responses. In the **Overall** context, [PTGDR2](/details-gene/11251) is most significantly expressed in [group 2 innate lymphoid cell](/details-cell/CL0001069), a key source of type 2 cytokines like IL-5 and IL-13. This high significance (CSI: 2.56) suggests it is a critical receptor for initiating or amplifying ILC2-mediated responses to allergens and pathogens. This finding is consistent with a large body of research identifying [PTGDR2](/details-gene/11251) as a selective marker for human Th2 cells ([Link](https://pubmed.ncbi.nlm.nih.gov/9973380)) and as a potent chemoattractant receptor for eosinophils and basophils ([Link](https://doi.org/10.1084/jem.193.2.255), [Link](https://doi.org/10.1182/blood.v98.6.1942)). The receptor's function is to recruit these key effector cells of allergic inflammation to sites where its ligand, PGD2, is abundant. Furthermore, its significant expression in [stromal cell](/details-cell/CL0000499) may indicate a role in mediating communication between hematopoietic immune cells and non-hematopoietic tissue cells, potentially influencing processes like tissue remodeling or fibrosis during chronic inflammation. ## Pathways and Molecular Function [PTGDR2](/details-gene/11251) is an integral plasma membrane protein ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) that functions as a [prostaglandin d receptor activity](/details-cell/GO0004956). It belongs to the Class A/1 (Rhodopsin-like) family of G protein-coupled receptors ([R-HSA-373076](https://reactome.org/content/detail/R-HSA-373076)). Upon binding PGD2, it couples to inhibitory G proteins (Gαi), initiating [G alpha (i) signalling events](/details-cell/R-HSA-418594) that lead to the inhibition of adenylate cyclase and a decrease in intracellular cAMP levels ([GO:0007193](https://www.ebi.ac.uk/QuickGO/term/GO:0007193)). This signaling cascade also involves [calcium-mediated signaling](/details-cell/GO0019722) and is crucial for its primary biological function: orchestrating [chemotaxis](/details-cell/GO0006935) of specific leukocyte populations. The molecular pharmacology and differential regulation of [PTGDR2](/details-gene/11251) signaling and trafficking have been characterized, highlighting its distinct properties compared to the other PGD2 receptor, PTGDR1 ([Link](https://doi.org/10.1038/sj.bjp.0704973), [Link](https://doi.org/10.1016/j.ejphar.2006.11.058)). This places the receptor as a central node in the [immune response](/details-cell/GO0006955), specifically translating the lipid mediator signal of PGD2 into directed cell migration and activation. ## Research Directions The specific expression of [PTGDR2](/details-gene/11251) on key cell types involved in allergic diseases makes it a subject of intense research and a compelling therapeutic target. **Proposed Hypotheses:** 1. Given its high significance in [group 2 innate lymphoid cell](/details-cell/CL0001069), signaling through [PTGDR2](/details-gene/11251) is a primary mechanism for the recruitment and activation of ILC2s in peripheral tissues (e.g., lung, gut) during the early phases of an allergic response, directly contributing to the amplification of type 2 inflammation. 2. The expression of [PTGDR2](/details-gene/11251) on [stromal cell](/details-cell/CL0000499), such as lung fibroblasts, mediates pro-fibrotic signaling in response to PGD2 released during chronic allergic inflammation, thereby contributing to airway or tissue remodeling seen in severe asthma. **Key Experimental Approach:** To test the first hypothesis regarding the role of [PTGDR2](/details-gene/11251) in ILC2 function, a mouse model of allergic airway inflammation (e.g., house dust mite or papain-induced) could be employed. Wild-type and *Ptgdr2*-knockout mice would be sensitized and challenged. The impact of [PTGDR2](/details-gene/11251) ablation could be assessed by quantifying ILC2 numbers, activation markers (e.g., ICOS, KLRG1), and intracellular cytokine production (IL-5, IL-13) in the lung tissue and bronchoalveolar lavage fluid using multi-parameter flow cytometry. Concurrently, RNA-seq on sorted lung ILC2s from both genotypes would reveal the downstream transcriptional programs regulated by [PTGDR2](/details-gene/11251) signaling. **Therapeutic Potential:** [PTGDR2](/details-gene/11251) is a highly attractive therapeutic target for type 2 inflammatory diseases, including asthma, atopic dermatitis, and eosinophilic esophagitis. Its restricted expression on key pro-inflammatory effector cells suggests that targeting it could offer high efficacy with a favorable safety profile. The therapeutic strategy is **inhibition** via small molecule antagonists that block PGD2 binding. Several oral antagonists for [PTGDR2](/details-gene/11251) have been developed and tested in clinical trials, aiming to reduce the recruitment and activation of eosinophils, basophils, and Th2/ILC2 cells, thereby dampening the allergic inflammatory cascade.

Genular Protein ID: 1437236942

Symbol: PD2R2_HUMAN

Name: Prostaglandin D2 receptor 2

UniProtKB Accession Codes:

Q9Y5Y4 O94765 Q4QRI6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 9 DrugCentral 1 EMBL 6 Ensembl 1 GO 15 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 3 PDBsum 3 PRINTS 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissLipids 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10036181

Title: Discovery of three novel orphan G-protein-coupled receptors.

PubMed ID: 10036181

DOI: 10.1006/geno.1998.5655

PubMed ID: 9973380

Title: Selective expression of a novel surface molecule by human Th2 cells in vivo.

PubMed ID: 9973380

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11535533

Title: Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor.

PubMed ID: 11535533

DOI: 10.1182/blood.v98.6.1942

PubMed ID: 11168006

Title: A novel surface molecule of Th2- and Tc2-type cells, CRTH2 expression on human peripheral and decidual CD4+ and CD8+ T cells during the early stage of pregnancy.

PubMed ID: 11168006

DOI: 10.1046/j.1365-2249.2001.01422.x

PubMed ID: 11208866

Title: Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2.

PubMed ID: 11208866

DOI: 10.1084/jem.193.2.255

PubMed ID: 12466225

Title: Molecular pharmacology of the human prostaglandin D2 receptor, CRTH2.

PubMed ID: 12466225

DOI: 10.1038/sj.bjp.0704973

PubMed ID: 17196174

Title: Inhibition of PI3K and calcineurin suppresses chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)-dependent responses of Th2 lymphocytes to prostaglandin D(2).

PubMed ID: 17196174

DOI: 10.1016/j.bcp.2006.11.021

PubMed ID: 17207480

Title: Differential regulation of the signaling and trafficking of the two prostaglandin D2 receptors, prostanoid DP receptor and CRTH2.

PubMed ID: 17207480

DOI: 10.1016/j.ejphar.2006.11.058

PubMed ID: 20035740

Title: Characterization of C-terminal tail determinants involved in CRTH2 receptor trafficking: identification of a recycling motif.

PubMed ID: 20035740

DOI: 10.1016/j.ejphar.2009.12.022

Sequence Information:

  • Length: 395
  • Mass: 43268
  • Checksum: 99A63CBDA418DEC9
  • Sequence:
    • MSANATLKPL CPILEQMSRL QSHSNTSIRY IDHAAVLLHG LASLLGLVEN GVILFVVGCR 
MRQTVVTTWV LHLALSDLLA SASLPFFTYF LAVGHSWELG TTFCKLHSSI FFLNMFASGF 
LLSAISLDRC LQVVRPVWAQ NHRTVAAAHK VCLVLWALAV LNTVPYFVFR DTISRLDGRI 
MCYYNVLLLN PGPDRDATCN SRQVALAVSK FLLAFLVPLA IIASSHAAVS LRLQHRGRRR 
PGRFVRLVAA VVAAFALCWG PYHVFSLLEA RAHANPGLRP LVWRGLPFVT SLAFFNSVAN 
PVLYVLTCPD MLRKLRRSLR TVLESVLVDD SELGGAGSSR RRRTSSTARS ASPLALCSRP 
EEPRGPARLL GWLLGSCAAS PQTGPLNRAL SSTSS