Structural Organization of the Human Prostaglandin EP3Receptor 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 EP3-V and EP3-VI. The transcription initiation sites of the human EP3 gene were mapped 227 to approximately 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.