Structural organization of the human prostaglandin EP₃ receptor subtype gene (PTGER3)

Prostaglandin EP₃ receptor subtype is a seven-membrane-spanning protein with multiple C-terminal tails generated by alternative mRNA splicing. We report here the structural organization of the human EP₃ gene (PTGER3). The human EP₃ gene spanned more than 80 kb and was composed of 10 exons separated by nine introns. Exon 1 and the 5' 180-bp portion of exon 2 (exon 2a) encoded the seven transmembrane domains and 10 amino acid residues of the cytoplasmic tail, which are common to all EP₃ isoforms. The 3' 3461-bp portion of exon 2 (exon 2b) or combinations of exons 3-10 encoded the EP₃ isoform-specific C termini and formed their 3'-untranslated regions by multiple fashions of alternative mRNA splicing. Exons 2b, 4, 6, and 10 contained polyadenylation sites. The EP₃ gene formed nine distinct mRNAs encoding eight EP₃ isoforms, two of which were novel ones tentatively designated EP(3-V) and EP(3-VI). The transcription initiation sites of the human EP₃ gene were mapped 227 to ~231 bp upstream of the ATG start codon. The 360-bp 5'flanking region contained a TATA box-like sequence, a GC box, and several cis-acting regulatory elements. The present study provides insight into the molecular mechanisms underlying the prostanoid receptor family.