ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration

EMBO J. 1996 Apr 15;15(8):1784-91.


A cDNA encoding a second zinc transporter (ZnT-2) was isolated from a rat kidney cDNA expression library by complementation of a zinc-sensitive BHK cell line. The protein predicted from the open reading frame of ZnT-2 cDNA has 359 amino acids and initiates with a CTG codon. It resembles ZnT-1 (a plasma membrane protein that stimulates zinc efflux) in overall topology in that it has six membrane-spanning domains, a histidine-rich intracellular loop and a long C-terminal tail; however, the overall amino acid identity is only 26%. Unlike ZnT-1, which is in the plasma membrane and lowers cellular zinc by stimulating zinc efflux, ZnT-2 is localized on vesicles and allows the zinc-sensitive BHK cells to accumulate zinc to levels that are much higher than non-transformed cells can tolerate. Zinc was visualized within these vesicles with zinquin, a zinc-specific fluorescent probe. The intracellular compartment that accumulates zinc is acidic as revealed by staining with acridine orange or LysoTracker. Prolonged exposure of cells expressing ZnT-2 to zinc causes an accretion of intracellular vesicles. We suggest that ZnT-2 protects these cells from zinc toxicity by facilitating zinc transport into an endosomal/lysosomal compartment.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport, Active
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Cation Transport Proteins*
  • Cell Line
  • Chromosome Mapping
  • Cricetinae
  • DNA, Complementary / genetics
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Muridae
  • Mutation
  • Rats
  • Sequence Homology, Amino Acid
  • Subcellular Fractions / metabolism
  • Transfection
  • Zinc / metabolism*
  • Zinc / toxicity


  • Carrier Proteins
  • Cation Transport Proteins
  • DNA, Complementary
  • Membrane Proteins
  • Slc30a1 protein, mouse
  • Slc30a2 protein, rat
  • Slc30a1 protein, rat
  • Zinc

Associated data

  • GENBANK/U50927