Functional characterization of two novel mammalian electrogenic proton-dependent amino acid cotransporters

J Biol Chem. 2002 Jun 21;277(25):22966-73. doi: 10.1074/jbc.M200374200. Epub 2002 Apr 16.


We cloned two cDNAs encoding proton/amino acid cotransporters, designated as mPAT1 and mPAT2, from murine tissues. They were identified by sequence similarity to the amino acid/auxin permease family member of lower eukaryotes. We functionally characterized both transporters by flux studies and electrophysiology after expression in Xenopus laevis oocytes. Both mPAT1 and mPAT2 induced a pH-dependent electrogenic transport activity for small amino acids (glycine, alanine, and proline) that is altered by membrane potential. Direct evidence for amino acid/H(+)-symport was shown by intracellular acidification, and a flux coupling stoichiometry for proline/H(+)-symport of 1:1 was determined for both transporters. Besides small apolar L-amino acids, the transporters also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid. The mPAT1 transporter, the murine orthologue of the recently cloned rat LYAAT-1 transporter, can be considered as a low affinity system when compared with mPAT2. The mRNA of mPAT1 is highly expressed in small intestine, colon, kidney, and brain; the mPAT2-mRNA is mainly found in heart and lung. Phenotypically, the PAT1 transporter possesses the same functional characteristics as the previously described proton-dependent amino acid transport process in apical membranes of intestinal and renal epithelial cells.

MeSH terms

  • Alanine / chemistry
  • Amino Acid Sequence
  • Amino Acid Transport Systems, Neutral*
  • Amino Acids / chemistry
  • Amino Acids / metabolism
  • Animals
  • Biological Transport
  • Blotting, Northern
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Electrophysiology
  • Epithelial Cells / metabolism
  • Glycine / chemistry
  • Green Fluorescent Proteins
  • HeLa Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Ions
  • Kinetics
  • Luminescent Proteins / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / metabolism
  • Membrane Transport Proteins*
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Proline / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Complementary / metabolism
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Sulfate Transporters
  • Symporters*
  • Tissue Distribution
  • Transfection
  • Xenopus laevis


  • Amino Acid Transport Systems, Neutral
  • Amino Acids
  • Carrier Proteins
  • DNA, Complementary
  • Ions
  • Luminescent Proteins
  • Membrane Proteins
  • Membrane Transport Proteins
  • RNA, Complementary
  • RNA, Messenger
  • SLC26A6 protein, human
  • Slc36a2 protein, mouse
  • Sulfate Transporters
  • Symporters
  • Green Fluorescent Proteins
  • Proline
  • Alanine
  • Glycine

Associated data

  • GENBANK/AF453743
  • GENBANK/AF453744