HUMAN INTESTINAL H+ PEPTIDE COTRANSPORTER - CLONING, FUNCTIONAL EXPRESSION, AND CHROMOSOMAL LOCALIZATION/

In mammalian small intestine, a H+-coupled peptide transporter is resp onsible for the absorption of small peptides arising from digestion of dietary proteins. Recently a cDNA clone encoding a H+/peptide cotrans porter has been isolated from a rabbit intestinal cDNA library (Fei, Y , J., Kanai, Y., Nussberger, S., Ganapathy, V., Leibach, F. H., Romero , M. F., Singh, S. K., Boron, W. F., and Hediger, M. A. (1994) Nature 368, 563-566). Screening of a human intestinal cDNA library with a pro be derived from the rabbit H+/peptide cotransporter cDNA resulted in t he identification of a cDNA which when expressed in HeLa cells or in X enopus laevis oocytes induced H+-dependent peptide transport activity. The predicted protein consists of 708 amino acids with 12 membrane-sp anning domains and two putative sites for protein kinase C-dependent p hosphorylation. The cDNA-induced transport process accepts dipeptides, tripeptides, and amino beta-lactam antibiotics but not free amino aci ds as substrates. The human H+/peptide cotransporter exhibits a high d egree of homology (81% identity and 92% similarity) to the rabbit H+/p eptide cotransporter. But surprisingly these transporters show only a weak homology to the H+-coupled peptide transport proteins present in bacteria and yeast. Chromosomal assignment studies with somatic cell h ybrid analysis and in situ hybridization have located the gene encodin g the cloned human H+/peptide cotransporter to chromosome 13 q33-->q34 .