Vol. 183, No. 2, 1992 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS March 16, 1992 Pages 821-828 Human Intestinal Mucin-like Protein (MLP) is Homologous With Rat MLP in the C-Terminal Region, and is Encoded by a Gene on Chromosome 11 p US1 G. Xu, L. Huan, I. Khatri, U.S. Satian, D. McCool, D. Wang, C. Jones*, G. Forstner, and J. ForstnerZ Research Institute, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8 and University of Toronto, Toronto, Ontario, Canada *Eleanor Roosevelt Institute, Denver, Colorado Received January 27, 1992 SUMMARY: A cDNA specific for a human intestinal mucin (MLP) wasamplified by PCR from cDNA of cultured human colonic adenocarcinoma cells, LS174T. The human cDNA shared high sequence homology with a corresponding rat intestinalmucin (MLP) cDNA in the 3’ terminal region, and hybridized to the same mRNA (- 9.0 Kb) that wasrecognized by a probefor the MUC-2 human intestinalmucin gene. The gene encoding our human mucin peptide alsomapped to chromosome 11 p 15.5, the known locusof MUC-2. Our findings suggest that humanMLP and MUC-2 areencoded by the same gene andthat rat and human intestinalmucin share a common C-terminal aminoacid structure. Q 1992 Academic Press, ~nc. Purified intestinal mucins of human,rabbit, rat and other species, have beenshownto producetwo major components by SDSPAGE underreducing conditions (1). One of these,a glycopeptideof Mr 118,000,has beentermeda putative ‘link’ glycopeptide on the assumption that it is involved in some manner in disulfide-linkedpolymerization of mucin molecules (2,3). Polymerization in turn is requiredfor the development of the viscoelastic properties which allow mucinsto act asa protective lubricant over epithelial surfaces. In a recent report (4) we have identified the primary peptidestructureof the 118kDa glycopeptide of rat intestinal mucin, and shownthat it represents the cysteine-rich carboxyl terminal 689 amino acidsof a very much larger mucin-like peptide (MLP). This is the first car-boxy1 terminal sequence to be reportedfor an intestinalmucin. A peptide bond cleavage site waspresent at the N-terminal proline of the 118kDa ‘link’ region which permittedisolation of this component from thiol reducednative mucin. Northern blots revealed a mRNA of approximately ‘;, Kb for MLP. There was no homology of the C-terminus of rat MLP with published sequences ot tandem repeatand flanking regions of either of the two human intestinalmucins MUC-2 or ML’C- 1 Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. M86523. *To whom correspondence shouldbe addressed. Fax (416) 591-5022.