Expression cloning of a mammalian proton-coupled oligopeptide transporter

Nature. 1994 Apr 7;368(6471):563-6. doi: 10.1038/368563a0.


In mammals, active transport of organic solutes across plasma membranes was thought to be primarily driven by the Na+ gradient. Here we report the cloning and functional characterization of a H(+)-coupled transporter of oligopeptides and peptide-derived antibiotics from rabbit small intestine. This new protein, named PepT1, displays an unusually broad substrate specificity. PepT1-mediated uptake is electrogenic, independent of extracellular Na+, K+ and Cl-, and of membrane potential. PepT1 messenger RNA was found in intestine, kidney and liver and in small amounts in brain. In the intestine, the PepT1 pathway constitutes a major mechanism for absorption of the products of protein digestion. To our knowledge, the PepT1 primary structure is the first reported for a proton-coupled organic solute transporter in vertebrates and represents an interesting evolutionary link between prokaryotic H(+)-coupled and vertebrate Na(+)-coupled transporters of organic solutes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • Intestine, Small / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Membrane Potentials
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Oligopeptides / metabolism*
  • Oocytes
  • Peptide Transporter 1
  • Protein Conformation
  • Rabbits
  • Symporters*
  • Xenopus


  • Carrier Proteins
  • Membrane Proteins
  • Oligopeptides
  • Peptide Transporter 1
  • Symporters

Associated data

  • GENBANK/U06467