Complete sequence of the human mucin MUC4: a putative cell membrane-associated mucin

The MUC4 gene, which encodes a human epithelial mucin, is expressed in vari ous epithelial tissues, just as well in adult as in poorly differentiated c ells in the embryo and fetus. Its N-terminus and central sequences have pre viously been reported as comprising a 27-residue peptide signal, followed b y a large domain varying in length from 3285 to 7285 amino acid residues. T he present study establishes the whole coding sequence of MUC4 in which the C-terminus is 1156 amino acid residues long and shares a high degree of si milarity with the rat sialomucin complex (SMC). SMC is a heterodimeric glyc oprotein complex composed of mucin (ascites sialoglycoprotein 1, ASGP-1) an d transmembrane (ASGP-2) subunits. The same organization is found in MUC4, where the presence of a GlyAspProHis proteolytic site may cleave the large precursor into two subunits, MUC4 alpha and MUC4 beta. Like ASGP-2, which b inds the receptor tyrosine kinase p185(neu), MUC4 beta possesses two epider mal growth factor-like domains, a transmembrane sequence and a potential ph osphorylated site. MUC4, the human homologue of rat SMC, may be a heterodim eric bifunctional cell-surface glycoprotein of 2.12 mu m. These results con fer a new biological role for MUC4 as a ligand for ErbB2 in cell signalling .