Primary Structure of the Human Proenkephalin Gene

The nucleotide sequence of a 6.8-kb region of human DNA containing the proenkephalin gene and flanking regions is reported. The gene consists of four exons separated by three introns and spans approximately 5.3 kb of DNA. Location and identification of several repetitive DNA sequences within and flanking the gene are also described. The distribution of CpG dinucleotides as well as the extent of CpG methylation at several restriction sites within and surrounding the gene is also presented. The structural organization of the human proenkephalin gene exhibits striking similarities to the organization of the human pro-opiomelanocortin (POMC) gene. Nucleotide sequence homologies suggest that two opioid peptide precursors, proenkephalin and prodynorphin, may have arisen by duplication from a common ancestral gene.