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Gene and Protein Information | ||||||
class A G protein-coupled receptor | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | 7 | 390 | 1p31.1 | PTGER3 | prostaglandin E receptor 3 | 2,57-58,60,104,148 |
Mouse | 7 | 365 | 3 81.32 cM | Ptger3 | prostaglandin E receptor 3 (subtype EP3) | 119,126 |
Rat | 7 | 365 | 2q45 | Ptger3 | prostaglandin E receptor 3 | 16,127 |
Gene and Protein Information Comments | ||||||
Many isoforms are described for the EP3 receptor due to mRNA splicing variants. NC-IUPHAR nomenclature for these isoforms should be respected- see the "Biologically Significant Variants" section below. |
Previous and Unofficial Names |
PGE receptor EP3 subtype | prostaglandin E receptor 3 | prostanoid EP3 receptor |
Database Links | |
Specialist databases | |
GPCRdb | pe2r3_human (Hs), pe2r3_mouse (Mm), pe2r3_rat (Rn) |
Other databases | |
Alphafold | P43115 (Hs), P30557 (Mm), P34980 (Rn) |
ChEMBL Target | CHEMBL3710 (Hs), CHEMBL4336 (Mm), CHEMBL5674 (Rn) |
DrugBank Target | P43115 (Hs) |
Ensembl Gene | ENSG00000050628 (Hs), ENSMUSG00000040016 (Mm), ENSRNOG00000010325 (Rn) |
Entrez Gene | 5733 (Hs), 19218 (Mm), 24929 (Rn) |
Human Protein Atlas | ENSG00000050628 (Hs) |
KEGG Gene | hsa:5733 (Hs), mmu:19218 (Mm), rno:24929 (Rn) |
OMIM | 176806 (Hs) |
Pharos | P43115 (Hs) |
RefSeq Nucleotide | NM_198716 (Hs), NM_001126044 (Hs), NM_198714 (Hs), NM_198717 (Hs), NM_198718 (Hs), NM_198719 (Hs), NR_028293 (Hs), NR_028294 (Hs), NM_198715 (Hs), NM_011196 (Mm), NM_012704 (Rn) |
RefSeq Protein | NP_001119516 (Hs), NP_035326 (Mm), NP_036836 (Rn) |
UniProtKB | P43115 (Hs), P30557 (Mm), P34980 (Rn) |
Wikipedia | PTGER3 (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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
The pKi for endogenous agonists, PGE2 and PGE1 are dependent on EP3 receptor isoform: PGE2 pKi 9.1 for EP3III [1]; PGE1 pKi 9.0 (rat) for EP3alpha [16]. Further potent and selective ligands of the human EP3 receptor have been identified, see [32-33,51]. Sulprostone has been commonly used as an EP3 agonist but shows considerable EP1 agonism [22]; SC46275 [48,108] and ONO-AE-248 [19] are more selective agents. ONO-AP-324 is closely related to the non-prostanoid prostacyclin mimetic ONO-1301; it shows EP3 partial agonism on smooth muscle preparations, while retaining a small degree of IP agonism [48]. Although M&B28767 is a highly potent EP3 agonist, it also shows significant TP agonism [66] In the mouse, the three EP3 isoforms show similar ligand binding properties but have different signal transduction properties [121]. Reference [114] uses human platelet preparations instead of transfected cells. Agonist misoprostol is an effective gastric ulcer therapy [102,106]. |
Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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View species-specific antagonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Further potent and selective ligands of the human EP3 receptor have been identified, see [32-33,51]. L-796,106 (pA2 = 7.4 - 8.10) [21,40] and ONO-AE3-240 [4,125] are recently developed selective EP3 antagonists. Care is required in the use of L-826266 and DG-041 owing to their high lipophilicity [49]. Antagonist DG-04, a potential inhibitor of human platelet aggregation, is currently in human clinical trials for the treatment of atherothrombosis [30,116]. |
Immunopharmacology Comments |
Foudi et al. (2012) [28] review the presence and role of EP1-4 receptors in human inflammation and immune cells. Studies in mice suggest that EP3 receptors may participate in reducing allergic reactivity. |
Immuno Process Associations | ||
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Primary Transduction Mechanisms | |
Transducer | Effector/Response |
Gi/Go family | Adenylyl cyclase inhibition |
References: 5,90,107,112 |
Secondary Transduction Mechanisms | |
Transducer | Effector/Response |
Gq/G11 family | Phospholipase C stimulation |
References: 5,147 |
Tissue Distribution | ||||||||
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Tissue Distribution Comments | ||||||||
Prostanoid receptor antibodies, are not very selective for immunochemistry experiments, results with other experimental approaches in parallel are necessary. |
Expression Datasets | |
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Physiological Functions | ||||||||
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Physiological Consequences of Altering Gene Expression | ||||||||||
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Phenotypes, Alleles and Disease Models | Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Clinically-Relevant Mutations and Pathophysiology | ||||||||||||||||||
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Biologically Significant Variants | ||||||||||||
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Biologically Significant Variant Comments | ||||||||||||
List of EP3 variants with their respective mRNA and protein RefSeq IDs Human variants: EP3-Ia (transcript variant 9, NM_198719; NP_942012), EP3-Ib (transcript variant 4, NM_198714; NP_942007), EP3-Ic (transcript variant 11, NM_001126044; NP_001119516), EP3-II (transcript variant 5, NM_198715;NP_942008), EP3-III (transcript variant 7, NM_198717; NP_942010), EP3-IV (transcript variant 6, NM_198716; NP_942009), EP3-e (transcript variant 8, NM_198718, NP_942011) Mouse variants: EP3α (isoform CRA_a) EDL11860, EP3β (isoform CRA_c) EDL11862;NP_035326, EP3γ (isoform CRA_b) EDL11861 Rat variants: EP3α (isoform CRA_b) EDL82565, EP3β (isoform CRA_c) EDL82566;NP_036836EP3γ (isoform CRA_a) EDL82564, EP3δ (isoform CRA_d) EDL82567 Notes: Isoform CRA_ a, b, c and d correspond to the nomenclature found in NCBI Nucleotide. NCBI describe human transcript variants 1-3 (corresponding previously to EP3-V; EP3-VI and EP3-f) as "non-coding because the use of the 5'-most supported translational start codon, as used in variant 7, renders the transcript a candidate for nonsense-mediated mRNA decay". In the article by Kotani et al (1997) EP3e amino acid sequence is incomplete, 25 amino acids are missing [58]. |
1. Abramovitz M, Adam M, Boie Y, Carrière M, Denis D, Godbout C, Lamontagne S, Rochette C, Sawyer N, Tremblay NM et al.. (2000) The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs. Biochim Biophys Acta, 1483 (2): 285-93. [PMID:10634944]
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