| 2.A.5 The Zinc (Zn2+)-Iron (Fe2+) Permease (ZIP) Family
Members of the ZIP family consist of 220-650 amino acyl residues with eight putative transmembrane spanners. They are derived from animals, plants and yeast, bacteria and archaea. They comprise a diverse family, with several paralogues in any one organism (e.g., twelve in humans, at least five in Caenorhabditis elegans and Arabidopsis thaliana, and two in Saccharomyces cervisiae). The two S. cerevisiae proteins, Zrt1 and Zrt2, both probably transport Zn2+ with high specificity, but Zrt1 transports Zn2+ with ten-fold higher affinity than Zrt2. Some members of the ZIP family have been shown to transport Zn2+ while others transport Fe2+, and at least one transports a range of metal ions. One human protein member of the ZIP family is designated "growth arrest inducible gene product," but its presumed transport activity has not been identified. A second human protein, Zip4, is a Zn2+ uptake permease and a disease protein.
The energy source for transport has not been characterized, but these systems probably function as secondary carriers. In one study, uptake of Zn2+ via the hZip2 permease was energy independent, independent of Na+ and K+ gradients, but stimulated by HCO3- (Gaither and Eide, 2000). The authors propose a Zn2+:HCO3- symport mechanism. hZip1 is the major Zn2+ uptake system in many human tissues (Gaither and Eide, 2001).
The generalized transport reaction for members of the ZIP family is:
Me2+ (out) + (pmf) → Me2+ (in).
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| References: |
Breitwieser, W., C. Price, and T. Schuster. (1993). Identification of a gene encoding a novel zinc finger protein in Saccharomyces cerevisiae. Yeast 9: 551-556.
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Dufner-Beattie, J., F. Wang, Y.M. Kuo, J. Gitschier, D. Eide, and G.K. Andrews. (2003). The Acrodermatitis enteropathica gene ZIP4 encodes a tissue-specific, zinc-regulated zinc transporter in mice. J. Biol Chem. 278: 33474-33481.
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Eide, D. and M.L. Guerinot. (1997). Metal ion uptake in eukaryotes. ASM News 63: 199-205.
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Eide, D., M. Broderius, J. Fett, and M.L. Guerinot. (1996). A novel iron-regulated metal transporter from plants identified by functional expression in yeast. Proc. Natl. Acad. Sci. USA 93: 5624-5628.
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Eng, B.H., M.L. Guerinot, D. Eide, and M.H. Saier, Jr. (1998). Sequence analyses and phylogenetic characterization of the ZIP family of metal ion transport proteins. J. Membr. Biol. 166: 1-7.
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Gaither, L.A. and D.J. Eide. (2000). Functional expression of the human hZIP2 zinc transporter. J. Biol. Chem. 275: 5560-5564.
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Gaither, L.A. and D.J. Eide. (2001). The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. J. Biol. Chem. 276: 22258-22264.
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Korshunova, Y.O., D. Eide, W.G. Clark, M.L. Guerinot, and H.B. Pakrasi. (1999). The IRT1 protein from Arabidopsis thaliana is a metal transporter with a broad substrate range. Plant Mol. Biol. 40: 37-44.
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Lin, S.J. and V.C. Culotta. (1996). Suppression of oxidative damage by Saccharomyces cerevisiae ATX2, which encodes a manganese-trafficking protein that localizes to Golgi-like vesicles. Mol. Cell. Biol. 16: 6303-6312.
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Radisky, D. and J. Kaplan. (1999). Regulation of transition metal transport across the yeast plasma membrane. J. Biol. Chem. 274: 4481-4484.
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Taylor, K.M. and R.I. Nicholson. (2003). The LZT proteins: the LIV-1 subfamily of zinc transporters. Biochim. Biophys. Acta 1611: 16-30.
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Yamashita, S., C. Miyagi, T. Fukada, N. Kagara, Y.-S. Che, and T. Hirano. (2004). Zinc transporter LIVI controls epithelial-mesenchymal transition in zebrafish gastrula organizer. Nature 429: 298-302.
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Zhao, H. and D. Eide. (1996). The ZRT2 gene encodes the low affinity zinc transporter in Saccharomyces cerevisiae. J. Biol. Chem. 271: 23203-23210.
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| Examples: |
| TC# | Name | Organismal Type | Example |
| 2.A.5.1.1 | High affinity zinc uptake transporter, Zrt1 | Yeast, animals, plants | Zrt1 of Saccharomyces cerevisiae |
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| 2.A.5.1.2 | Iron regulated metal ion uptake transporter, Irt1 (Fe2+, Mn2+, Zn2+ and possibly Cd2+ and Co2+ are transported) | Plants, animals, yeast | Irt1 of Arabidopsis thaliana |
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| 2.A.5.2.1 | Golgi Mn2+ homeostasis protein (probably pumps Mn2+ into cytoplasm), ATX2 | Yeast | ATX2 of Saccharomyces cerevisiae |
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| 2.A.5.3.1 | Growth arrest-inducible protein | Animals | Growth arrest-inducible protein of Homo sapiens |
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| 2.A.5.4.1 | Zip4 Zn2+ uptake transporter (Acrodermatitis enteropathica zinc-deficiency disease protein) (Dufner-Beattie et al., 2003) | Animals | Zip4 of Homo sapiens |
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| 2.A.5.4.2 | Zinc transporter, LIV1 (essential for the nuclear localization of the zinc-finger protein Snail, a master regulator of the epithelial-mesenchymal transition in zebrafish gastrulation) (Yamashita et al., 2004) | Animals | LIV1 in Danio rerio (BAD18961) |
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