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Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 488 | 5p13.1 | PTGER4 | prostaglandin E receptor 4 | 6,12 |
| Mouse | 7 | 513 | 15 1.99 cM | Ptger4 | prostaglandin E receptor 4 (subtype EP4) | 48 |
| Rat | 7 | 488 | 2q16 | Ptger4 | prostaglandin E receptor 4 | 18,116 |
| Previous and Unofficial Names |
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| EP2 [6,12,43,48,116] | PGE receptor EP4 subtype | prostanoid EP4 receptor | |
| Database Links |
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| Specialist databases | |
| GPCRdb | pe2r4_human (Hs), pe2r4_mouse (Mm), pe2r4_rat (Rn) |
| Other databases | |
| Alphafold | P35408 (Hs), P32240 (Mm), P43114 (Rn) |
| ChEMBL Target | CHEMBL1836 (Hs), CHEMBL2489 (Mm), CHEMBL4086 (Rn) |
| DrugBank Target | P35408 (Hs) |
| Ensembl Gene | ENSG00000171522 (Hs), ENSMUSG00000039942 (Mm), ENSRNOG00000013240 (Rn) |
| Entrez Gene | 5734 (Hs), 19219 (Mm), 84023 (Rn) |
| Human Protein Atlas | ENSG00000171522 (Hs) |
| KEGG Gene | hsa:5734 (Hs), mmu:19219 (Mm), rno:84023 (Rn) |
| OMIM | 601586 (Hs) |
| Pharos | P35408 (Hs) |
| RefSeq Nucleotide | NM_000958 (Hs), NM_008965 (Mm), NM_032076 (Rn) |
| RefSeq Protein | NP_000949 (Hs), NP_032991 (Mm), NP_114465 (Rn) |
| UniProtKB | P35408 (Hs), P32240 (Mm), P43114 (Rn) |
| Wikipedia | PTGER4 (Hs) |
| Selected 3D Structures |
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| Natural/Endogenous Ligands |
| PGD2 |
| PGE1 |
| PGE2 |
| PGF2α |
| PGI2 |
| Comments: PGE2 is the principal endogenous agonist |
| Potency order of endogenous ligands |
| PGE2 = PGE1 > PGF2α, PGI2 > PGD2, thromboxane A2 |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ONO-AE1-329, TCS-2510 and L-902688 are useful selective EP4 agonists. Analogues with optimized EP2 / EP4 agonism have been recently developed [59]. ONO-4232, a selective EP4 agonist is in Phase I clinical trials in acute heart failure [133]. A conjugate of an EP4a agonist that reverses osteopenia in a rat model [74] should not be confused with the L-161,982 (EP4A) antagonist in the table below. Chemistry of EP4 agonist conjugates in disclosed in Arns et al. (2012) [7]. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The archetypal EP4 antagonist AH-23848 has been superseded by more potent and selective agents: CJ-023423, GW-627368, L-161982, ONO-AE3-208. The NH group in antagonists containing an acyl-sulphonamido moiety (e.g. GW-627368) is acidic. The EP4 antagonist grapiprant is approved for the treatment of pain and inflammation in osteoarthritis in dogs [110]. |
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| Allosteric Modulators | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immunopharmacology Comments |
| The EP4 prostanoid receptor is one of four receptor subtypes for prostaglandin PGE2. The anti- and pro-inflammatory (and non-inflammatory) activities of this receptor are reviewed in [144]. Foudi et al. (2012) [35] review the presence and role of EP1-4 receptors in human inflammation and immune cells. The PGE2/EP4 receptor axis appears to act as an amplifier of cytokine (like IL-6) activity and induces the differentiation and expansion of inflammatory T-helper (Th) lymphocytes. Results from several mouse models indicate that the PGE2/EP4 receptor axis is important in regulating the inflammatory response across a range of tissues [29,31,112,122,142]. PGE2, acting via EP2 and EP4 receptors in synovial tissue appears to contribute to the progression of rheumatoid arthritis (RA) in a rat model [139]. Blocking EP4 and EP2 using their antagonists or genetically modified animals prevents inflammation in CNS, gut and skin in animal models for multiple sclerosis, colitis, psoriasis, atopic dermatitis and contact hypersensitivity [31,70,77,112,140]. EP4 antagonists with anti-inflammatory action are discussed in [56]. CR6086 is an example of a EP4 antagonist that is in clinical development for RA. The EP4 receptor is discussed in this review of immuno-oncology [2].The roles of PGE2 in chronic immune-mediated inflammation is reviewed here [141]. |
| Immuno Process Associations | ||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| References: 94 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gi/Go family | Other - See Comments |
| Comments: A second EP4 signaling pathway is PI3K dependent via G protein Gi activation. | |
| References: 38,40,111,114 | |
| Tissue Distribution
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| Functional Assays
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| Physiological Consequences of Altering Gene Expression
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| Physiological Consequences of Altering Gene Expression Comments | ||||||||||
| Deletion of this single gene has been reported to create a mouse model of patent ductus arteriosus, a congenital heart disorder where the ductus arteriosus fails to close spontaneously in neonates (see OMIM:607411) [96]. | ||||||||||
| Phenotypes, Alleles and Disease Models
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The recombinant EP4 receptor was originally identified as EP2 [12,48]. The EP2 and EP4 receptors are thought to mediate most of the hemodynamic responses to PGE2 in the female but not the male mouse [9]. |
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target has curated data in GtoImmuPdb
