Structural organization of the human prostaglandin EP(3) receptor subtype gene (PTGER3)

Prostaglandin EP(3) 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 EP(3) gene (PTGER3). The human EP(3) 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 EP(3) isoforms. The 3' 3461-bp portion of exon 2 (exon 2b) or combinations of exons 3-10 encoded the EP(3) 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 EP(3) gene formed nine distinct mRNAs encoding eight EP(3) isoforms, two of which were novel ones tentatively designated EP(3-V) and EP(3-VI). The transcription initiation sites of the human EP(3) gene were mapped 227 to similar to 251 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. (C) 1997 Academic Press.