Details for: PTGIR

Gene ID: 5739

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: PTGIR

Ensembl ID: ENSG00000160013

Description: prostaglandin I2 receptor

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • fibroblast of lung CL0002553
    CSI 11.99
    rCSI 11.16%
    PRS 84.2
  • tracheobronchial smooth muscle cell CL0019019
    CSI 8.07
    rCSI 14.23%
    PRS 87.85
  • hepatic stellate cell CL0000632
    CSI 6.78
    rCSI 25.38%
    PRS 76.43
  • CD14-positive, CD16-positive monocyte CL0002397
    CSI 6.54
    rCSI 8.57%
    PRS 92.22
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 6.38
    rCSI 7.73%
    PRS 63.97
  • megakaryocyte CL0000556
    CSI 6.36
    rCSI 27.59%
    PRS 87.48
  • cytotoxic T cell CL0000910
    CSI 4.71
    rCSI 27%
    PRS 85.57
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 4.61
    rCSI 3.55%
    PRS 86.4
  • bronchus fibroblast of lung CL2000093
    CSI 4.5
    rCSI 3.65%
    PRS 82.83
  • perivascular cell CL4033054
    CSI 4.39
    rCSI 6.01%
    PRS 87.57
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 3.92
    rCSI 4.74%
    PRS 89.96
  • lung pericyte CL0009089
    CSI 3.33
    rCSI 8.78%
    PRS 89.12
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.44
    rCSI 2.68%
    PRS 85.19
  • vascular associated smooth muscle cell CL0000359
    CSI 2.39
    rCSI 7.75%
    PRS 81.52
  • pancreatic stellate cell CL0002410
    CSI 2.16
    rCSI 12.54%
    PRS 86.5
  • fibroblast of cardiac tissue CL0002548
    CSI 2.09
    rCSI 10%
    PRS 83.59
  • platelet CL0000233
    CSI 2.02
    rCSI 8.39%
    PRS 80.62
  • adventitial cell CL0002503
    CSI 1.81
    rCSI 4.32%
    PRS 86.81
  • alveolar adventitial fibroblast CL4028006
    CSI 1.49
    rCSI 2.35%
    PRS 84.73
  • mesenchymal cell CL0008019
    CSI 1.36
    rCSI 3.46%
    PRS 77.22
  • basal cell of epidermis CL0002187
    CSI 1.34
    rCSI 2.37%
    PRS 52.67
  • helper T cell CL0000912
    CSI 1.17
    rCSI 1.65%
    PRS 81.58
  • microcirculation associated smooth muscle cell CL0008035
    CSI 1.16
    rCSI 3.36%
    PRS 82.6
  • dendritic cell, human CL0001056
    CSI 1.07
    rCSI 1.64%
    PRS 90.49
  • suprabasal keratinocyte CL4033013
    CSI 0.81
    rCSI 1.31%
    PRS 51.06
  • blood vessel smooth muscle cell CL0019018
    CSI 0.33
    rCSI 2.67%
    PRS 78.25
  • mesenchymal stem cell CL0000134
    CSI 0.17
    rCSI 1.82%
    PRS 87.62

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 The [PTGIR](/details-gene/5739) gene encodes the human prostacyclin (PGI2) receptor, a G-protein coupled receptor (GPCR) that plays a critical role in cardiovascular homeostasis and inflammation. As a member of the prostanoid receptor family, it mediates the effects of its ligand, prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. Initial cloning and characterization studies established its expression in the cardiovascular system ([Link](https://pubmed.ncbi.nlm.nih.gov/7923647/); [Link](https://doi.org/10.1016/s0021-9258(17)32697-2)). Expression data indicates that **Overall**, [PTGIR](/details-gene/5739) is most significantly expressed in mesenchymal cell types, particularly [fibroblast of lung](/details-cell/CL0002553) and [tracheobronchial smooth muscle cell](/details-cell/CL0019019), as well as in key hematopoietic lineages such as [megakaryocyte](/details-cell/CL0000556) and monocytes. This expression pattern is consistent with its established functions in regulating vascular tone, hemostasis, and immune responses. Clinically, it is associated with OMIM entry [600022](https://omim.org/entry/600022). ## Cellular Roles and Expression Landscape The expression profile of [PTGIR](/details-gene/5739) highlights its dual importance in structural tissue biology and hematopoiesis. **Overall**, the gene shows the highest significance in mesenchymal and stromal cells, underscored by its top rank in [fibroblast of lung](/details-cell/CL0002553) (CSI: 11.99), [tracheobronchial smooth muscle cell](/details-cell/CL0019019) (CSI: 8.07), and [hepatic stellate cell](/details-cell/CL0000632) (CSI: 6.78). This strong association with fibroblasts, smooth muscle cells, and perivascular cells ([perivascular cell](/details-cell/CL4033054), [lung pericyte](/details-cell/CL0009089)) points to a fundamental role in maintaining vascular and airway function, regulating blood pressure, and participating in tissue remodeling processes. Its function in negatively regulating smooth muscle cell proliferation ([GO:0048662](https://www.ebi.ac.uk/QuickGO/term/GO:0048662)) is directly supported by this expression pattern. Concurrently, [PTGIR](/details-gene/5739) demonstrates significant expression in specific immune and hematopoietic cell types. Its high significance in [megakaryocyte](/details-cell/CL0000556) (CSI: 6.36), the precursor to platelets, is consistent with its well-defined role in inhibiting platelet activation and aggregation, a cornerstone of hemostasis. Furthermore, its expression in monocyte populations, including [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) (CSI: 6.54), and lymphocyte subsets like [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) (CSI: 6.38) and [cytotoxic T cell](/details-cell/CL0000910) (CSI: 4.71), suggests a direct modulatory role in both innate and adaptive inflammatory responses. ## Pathways and Molecular Function [PTGIR](/details-gene/5739) functions as a canonical G-protein coupled receptor located on the [plasma membrane](/details-cell/GO:0005886). Its primary molecular function is [prostacyclin receptor activity](/details-cell/GO:0016501), which initiates a signaling cascade upon binding its ligand, PGI2. The receptor is predominantly coupled to G-alpha(s) proteins, leading to the activation of the [adenylate cyclase-activating g protein-coupled receptor signaling pathway](/details-cell/GO:0007189) and a subsequent increase in intracellular cyclic AMP (cAMP) levels. This is a central event in the [G alpha (s) signalling events](/details-cell/R-HSA-418555) pathway. The downstream effects of this cascade are pleiotropic and context-dependent, mediating key biological processes. In the context of the cardiovascular system, this signaling pathway is integral to [Hemostasis](/details-cell/R-HSA-109582), where it contributes to [Platelet homeostasis](/details-cell/R-HSA-418346) by inhibiting platelet aggregation. In vascular and airway tissues, the same pathway leads to smooth muscle relaxation, contributing to vasodilation and bronchodilation. Furthermore, its involvement in the [inflammatory response](/details-cell/GO:0006954) pathway, consistent with its expression in monocytes and T cells, indicates a role in modulating immune cell function and cytokine release. ## Research Directions The well-established role of [PTGIR](/details-gene/5739) in vasodilation and platelet inhibition has led to successful therapies, but its high expression in cell types central to fibrosis and immune regulation suggests untapped therapeutic potential. **Proposed Hypotheses:** 1. Given its high significance in multiple fibroblast and stellate cell populations ([fibroblast of lung](/details-cell/CL0002553), [hepatic stellate cell](/details-cell/CL0000632), [pancreatic stellate cell](/details-cell/CL0002410)), we hypothesize that **[PTGIR](/details-gene/5739) activation serves as a key endogenous anti-fibrotic signal.** Downregulation of [PTGIR](/details-gene/5739) or its ligand during chronic injury may be a critical step in the pathogenesis of fibrotic diseases like idiopathic pulmonary fibrosis (IPF) and liver cirrhosis by permitting unchecked fibroblast proliferation and extracellular matrix deposition. 2. The notable expression in pro-inflammatory [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) and [cytotoxic T cell](/details-cell/CL0000910) suggests that **[PTGIR](/details-gene/5739) signaling directly dampens effector functions in these cells.** We hypothesize that prostacyclin acts in a paracrine manner within inflamed tissues to limit immunopathology by inhibiting monocyte-to-macrophage differentiation or reducing the cytolytic activity of T cells. **Key Experimental Approach:** To test the first hypothesis regarding its anti-fibrotic role, a compelling experiment would be to **use an in vitro model of lung fibrosis.** Primary human lung fibroblasts isolated from healthy donors or IPF patients could be cultured and stimulated with the pro-fibrotic cytokine TGF-beta. The cells would be co-treated with a stable prostacyclin analog (e.g., iloprost, a [PTGIR](/details-gene/5739) agonist). Key readouts would include: * **Quantitative PCR and Western blotting** to measure the expression of fibrotic markers like alpha-smooth muscle actin (α-SMA), collagen type I (COL1A1), and fibronectin. * **Immunofluorescence microscopy** to visualize the formation of α-SMA-positive stress fibers, a hallmark of fibroblast-to-myofibroblast differentiation. A significant reduction in these fibrotic markers in the presence of the [PTGIR](/details-gene/5739) agonist would provide strong evidence for its direct anti-fibrotic activity. **Therapeutic Potential:** [PTGIR](/details-gene/5739) is already a validated and highly "druggable" therapeutic target, as demonstrated by the clinical use of prostacyclin analogs (agonists) for treating pulmonary arterial hypertension. The therapeutic strategy for this target is **activation (agonism)**, not inhibition. The expression data strongly supports expanding the therapeutic application of [PTGIR](/details-gene/5739) agonists to combat fibrotic diseases of the lung, liver, and other organs where fibroblasts and stellate cells drive pathology. Its role in modulating inflammation also suggests potential applications in autoimmune or chronic inflammatory conditions.

Genular Protein ID: 2583911810

Symbol: PI2R_HUMAN

Name: Prostacyclin receptor

UniProtKB Accession Codes:

P43119

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 6 DrugCentral 1 EMBL 6 EMDB 2 Ensembl 1 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 1 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 3 RefSeq 1 SABIO-RK 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7512962

Title: Cloning and expression of a cDNA for the human prostanoid IP receptor.

PubMed ID: 7512962

DOI: 10.1016/s0021-9258(17)32697-2

PubMed ID: 7514139

Title: Cloning and expression of a cDNA for the human prostacyclin receptor.

PubMed ID: 7514139

DOI: 10.1016/0014-5793(94)00355-6

PubMed ID: 7923647

Title: Molecular cloning of human prostacyclin receptor cDNA and its gene expression in the cardiovascular system.

PubMed ID: 7923647

DOI: 10.1161/01.cir.90.4.1643

PubMed ID: 7665161

Title: Structural organization and chromosomal assignment of the human prostacyclin receptor gene.

PubMed ID: 7665161

DOI: 10.1006/geno.1995.1016

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: 11895442

Title: Investigation of a functional requirement for isoprenylation by the human prostacyclin receptor.

PubMed ID: 11895442

DOI: 10.1046/j.1432-1327.2002.02817.x

PubMed ID: 12488443

Title: Palmitoylation of the human prostacyclin receptor. Functional implications of palmitoylation and isoprenylation.

PubMed ID: 12488443

DOI: 10.1074/jbc.m210637200

PubMed ID: 27613955

Title:

PubMed ID: 27613955

DOI: 10.1074/jbc.a116.210637

PubMed ID: 15194446

Title: Role of extracellular cysteine residues in dimerization/oligomerization of the human prostacyclin receptor.

PubMed ID: 15194446

DOI: 10.1016/j.ejphar.2004.04.041

Sequence Information:

  • Length: 386
  • Mass: 40956
  • Checksum: 2B6B0CDBACED1608
  • Sequence:
    • MADSCRNLTY VRGSVGPATS TLMFVAGVVG NGLALGILSA RRPARPSAFA VLVTGLAATD 
LLGTSFLSPA VFVAYARNSS LLGLARGGPA LCDAFAFAMT FFGLASMLIL FAMAVERCLA 
LSHPYLYAQL DGPRCARLAL PAIYAFCVLF CALPLLGLGQ HQQYCPGSWC FLRMRWAQPG 
GAAFSLAYAG LVALLVAAIF LCNGSVTLSL CRMYRQQKRH QGSLGPRPRT GEDEVDHLIL 
LALMTVVMAV CSLPLTIRCF TQAVAPDSSS EMGDLLAFRF YAFNPILDPW VFILFRKAVF 
QRLKLWVCCL CLGPAHGDSQ TPLSQLASGR RDPRAPSAPV GKEGSCVPLS AWGEGQVEPL 
PPTQQSSGSA VGTSSKAEAS VACSLC