Genomic organization and structure of the 3 ' region of human MUC3: Alternative splicing predicts membrane-bound and soluble forms of the mucin

The MUC3 gene encodes a large, glycosylated mucin produced by intestinal ep ithelial cells to form a protective barrier against the external environmen t. Recently published cDNA sequences for the carboyl-terminal region of MUC 3 polypeptide indicated that rodent Muc3 possesses two epidermal growth fac tor (EGF)-like domains, and putative transmembrane and cytoplasmic domains, whereas the sequence of human MUC3 predicted termination after the first E GF-like domain. Here we describe the complete genomic sequence encompassing the carboxyl terminal region of human MUC3, revealing the boundaries of 11 exons. RT-PCR and cDNA library cloning experiments indicate that the gene is alternatively spliced, yielding a major membrane-bound form as well as m ultiple soluble forms. Thus, this work indicates that both membrane-bound a nd soluble MUC3 mucin proteins are produced by alternative splicing of a si ngle gene. A potenially important polymorphism involving a Tyr residue with a proposed role in signalling is described as well, (C) 1999 Academic Pres s.