The major form of OPRM1, called MOR-1, is coded by exons 1, 2, 3, and 4 (1). Exon 1 codes for first transmembrane domain (TMH1) and exons 2 and 3 code for the TMH2 through TMH7. However, many 5′-end and 3′-end alternatively spliced forms of OPRM1 have also been cloned (2). A common splicing pattern among the 3′-end alternatively spliced forms involves the alternative C-terminus, coded by various exons, while all seven transmembrane domains that form the binding pocket are coded by exons 1, 2, and 3, stay intact. The structural difference at the C-terminus has been proposed to drive differential cellular signaling in response to receptor activation (1–5). Alternative splicing at the 5′-end results either in an alternative TMH1 domain (via alternative exon 11) or in isoforms that start from exon 2 (6, 7), which lack an amino acid sequence of approximately 90 amino acids (N-terminus, TMH1 and part of the first intracellular loop) (8) but retain the ligand binding pocket distributed across the conserved TMH2, TMH3, and TMH7 domains.
