Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. The reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene.

We previously identified a novel gene, reg (i.e. regenerating gene), in the screening of a rat regenerating islet-derived cDNA library, and isolated its human cDNA homologue which encodes a 166-amino acid protein (Terazono, K., Yamamoto, H., Takasawa, S., Shiga, K., Yonemura, Y., Tochino, Y., and Okamoto, H. (1988) J. Biol. Chem. 263, 2111-2114). In the present study, we have isolated the human reg gene, determined its complete nucleotide sequence, and examined its expression in human tissues. The functional human reg gene is a single copy gene, spans approximately 3.0 kilobase pairs, and is composed of six exons and five introns. TATA box and CCAAT box-like sequences are located at 27 and 100 base pairs upstream from the transcriptional initiation site. The human reg mRNA was detected predominantly in the pancreas, and at lower levels in the gastric mucosa and the kidney. Furthermore, the reg gene was found to be expressed ectopically in colon and rectal tumors. Immunoblot analysis demonstrated several molecular forms (15-18 kDa) of the reg protein in the pancreas. The 166-amino acid sequence encoded by the human reg gene contains the 144-amino acid sequence of pancreatic stone protein determined by De Caro et al. (De Caro, A. M., Adrich, Z., Fournet, B., Capon, C., Bonicel, J. J., De Caro, J. D., and Rovery, M. (1989) Biochim. Biophys. Acta 994, 281-284) and the partially determined 45-amino acid sequence of pancreatic thread protein (Gross, J., Carlson, R. I., Brauer, A. W., Margolies, M. N., Warshaw, A. L., and Wands, J. R. (1985) J. Clin. Invest. 76, 2115-2126), indicating that the reg protein, pancreatic stone protein, and pancreatic thread protein are simply different names for a single protein deriving from the reg gene.