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Gene Review

ZRT1  -  high-affinity Zn(2+) transporter ZRT1

Saccharomyces cerevisiae S288c

Synonyms: High-affinity zinc transport protein ZRT1, NRC376, YGL255W, Zinc-regulated transporter 1
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Disease relevance of ZRT1

  • Using mutant alleles defective for metal-responsive inactivation, we also show that Zrt1 inactivation may be an important mechanism for preventing cadmium uptake and toxicity in zinc-limited cells [1].

High impact information on ZRT1

  • While ZRT1 is maximally induced during zinc limitation, ZRT2 is repressed in low zinc but remains induced upon zinc supplementation [2].
  • We used a genetic approach to isolate mutants whose ZRT1 expression is no longer repressed in zinc-replete cells, and a new gene, ZAP1, was identified [3].
  • To further understand this process at a molecular level, we mapped a region of Zrt1 required for ubiquitination and endocytosis in response to zinc to a domain located on the intracellular surface of the plasma membrane [1].
  • During the transition from zinc-limiting to zinc-replete growth conditions (i.e. zinc shock), the Zrt1 transporter is ubiquitinated, endocytosed, and subsequently degraded in the vacuole [1].
  • We show here that post-translational inactivation of the yeast Zrt1 zinc uptake transporter is important for zinc homeostasis [1].

Biological context of ZRT1


Anatomical context of ZRT1


Associations of ZRT1 with chemical compounds

  • In this work, we verified that yeast cells deleted in ZRT1 were not capable of transporting cadmium, suggesting that the transport of this metal into the cell would be carried out through this zinc transporter [6].
  • Finally, mutation of a specific lysine residue in ZRT1 blocks both ubiquitination and endocytosis [5].

Other interactions of ZRT1

  • In yeast, zinc uptake is mediated by Zrt1p and Zrt2p, which belong to the ZIP family of metal transporters [7].
  • Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter [5].


  1. A cytosolic domain of the yeast Zrt1 zinc transporter is required for its post-translational inactivation in response to zinc and cadmium. Gitan, R.S., Shababi, M., Kramer, M., Eide, D.J. J. Biol. Chem. (2003) [Pubmed]
  2. The Zap1 transcriptional activator also acts as a repressor by binding downstream of the TATA box in ZRT2. Bird, A.J., Blankman, E., Stillman, D.J., Eide, D.J., Winge, D.R. EMBO J. (2004) [Pubmed]
  3. Zap1p, a metalloregulatory protein involved in zinc-responsive transcriptional regulation in Saccharomyces cerevisiae. Zhao, H., Eide, D.J. Mol. Cell. Biol. (1997) [Pubmed]
  4. Zinc-induced inactivation of the yeast ZRT1 zinc transporter occurs through endocytosis and vacuolar degradation. Gitan, R.S., Luo, H., Rodgers, J., Broderius, M., Eide, D. J. Biol. Chem. (1998) [Pubmed]
  5. Zinc-regulated ubiquitin conjugation signals endocytosis of the yeast ZRT1 zinc transporter. Gitan, R.S., Eide, D.J. Biochem. J. (2000) [Pubmed]
  6. Regulation of cadmium uptake by Saccharomyces cerevisiae. Gomes, D.S., Fragoso, L.C., Riger, C.J., Panek, A.D., Eleutherio, E.C. Biochim. Biophys. Acta (2002) [Pubmed]
  7. Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae. MacDiarmid, C.W., Gaither, L.A., Eide, D. EMBO J. (2000) [Pubmed]
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