PTGER3 Gene – Prostaglandin E Receptor 3 (EP3) | Function, Mutations & Disease Associations

PTGER3 (Prostaglandin E Receptor 3) encodes a G-protein-coupled receptor (GPCR) of the rhodopsin-like family that binds prostaglandin E2 (PGE2). The receptor, also known as EP3, mediates diverse physiological effects including smooth muscle contraction, inhibition of gastric acid secretion, modulation of neurotransmitter release, and regulation of immune responses. Multiple splice variants (EP3-I through EP3-IV) differ in their C-terminal tails, leading to distinct G-protein coupling and signaling outcomes. PTGER3 is implicated in pain perception, inflammation, cancer progression, and reproductive functions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Prostanoid signaling (Reactome: R-HSA-416476)

• GPCR downstream signaling (Reactome: R-HSA-388396)

• PGE2-induced pain sensitization (KEGG: hsa04742)

• cAMP signaling pathway (KEGG: hsa04024)

The PTGER3 protein (EP3 receptor) is a 390-amino-acid GPCR with seven transmembrane domains. It preferentially couples to Gi proteins, inhibiting adenylate cyclase and reducing intracellular cAMP levels. Alternative splicing generates four major isoforms (EP3-I, EP3-II, EP3-III, EP3-IV) that differ in the C-terminal intracellular tail, affecting desensitization, internalization, and G-protein selectivity. The receptor is widely expressed in kidney, lung, uterus, and brain, and plays a critical role in mediating PGE2 effects on pain, inflammation, and smooth muscle tone.