Identification of a novel membrane transporter associated with intracellular membranes by phenotypic complementation in the yeast Saccharomyces cerevisiae

J Biol Chem. 1996 Apr 19;271(16):9801-8. doi: 10.1074/jbc.271.16.9801.


A partial mouse cDNA was isolated by its ability to functionally complement a thymidine transport deficiency in plasma membranes of the yeast, Saccharomyces cerevisiae. The full-length cDNA encoded a previously unidentified 27-kDa protein (mouse transporter protein (MTP)) with four predicted transmembrane-spanning domains. MTP mRNA was detected in cells of several mammalian species, and its predicted protein sequence exhibited near identity (98%) with that of a human cDNA (HUMORF13). MTP and its homologs evidently reside in an intracellular membrane compartment because a protein (about 24 kDa) that was recognized by MTP-specific antibodies was observed in a subcellular fraction of rat hepatocytes enriched for Golgi membranes. Deletion of the hydrophilic C terminus of MTP, which encompassed two putative signal motifs for intracellular localization (Tyr-X-X-hydrophobic amino acid), allowed expression of recombinant protein (MTP deltaC) in plasma membranes of Xenopus laevis oocytes. MTP deltaC-expressing oocytes exhibited greater fragility than nonexpressing oocytes, and those that survived the experimental manipulations were capable of mediated uptake of thymidine, uridine, and adenosine. Thymidine uptake by MTP deltaC-expressing oocytes was inhibited by thymine and dTMP. MTP may function in the transport of nucleosides and/or nucleoside derivatives between the cytosol and the lumen of an intracellular membrane-bound compartment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • DNA Primers
  • DNA, Complementary
  • Female
  • Genetic Complementation Test
  • Humans
  • Leukemia L1210 / metabolism
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Membrane Transport Proteins*
  • Mice
  • Molecular Sequence Data
  • Oocytes / physiology
  • Phenotype
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • Rats
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Subcellular Fractions
  • Thymidine / metabolism
  • Tumor Cells, Cultured
  • Uridine / metabolism
  • Xenopus laevis


  • Carrier Proteins
  • DNA Primers
  • DNA, Complementary
  • Laptm4a protein, mouse
  • Membrane Proteins
  • Membrane Transport Proteins
  • RNA, Messenger
  • Adenosine
  • Thymidine
  • Uridine

Associated data

  • GENBANK/U34259