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SLC39A1  -  solute carrier family 39 (zinc...

Homo sapiens

Synonyms: CGI-08, CGI-71, IRT1, Solute carrier family 39 member 1, ZIP-1, ...
 
 
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Disease relevance of SLC39A1

  • First, we examined (65)Zn uptake activity in K562 erythroleukemia cells overexpressing hZIP1 [1].
  • We have evaluated 58 prostate cancer tissues in 2 major racial groups (30 from whites and 28 from African Americans) for their ability to express 2 major human zinc transporters, hZIP1 and hZIP2 [2].
  • We identified at least two zinc transporters in both human mesenchymal stem cells (MSCs) and in osteoblastic cells--the ubiquitous zinc transporter, ZIP1, and LIV-1, which was previously characterized as a protein that is expressed in breast cancer cells [3].
 

High impact information on SLC39A1

  • All three of these mouse ZIP proteins function to specifically increase the uptake of zinc in transfected cultured cells, similar to the previously demonstrated functions of human ZIP1 and ZIP2 (Gaither, L [4].
  • Moreover, consistent with its role in zinc uptake, hZIP1 protein was localized to the plasma membrane [1].
  • The observation that hZIP1 is the major zinc transporter in K562 cells, coupled with its expression in many normal cell types, indicates that hZIP1 plays an important role in zinc uptake in human tissues [1].
  • In this report, we describe the characterization of hZip2, a human zinc transporter identified by its similarity to zinc transporters recently characterized in fungi and plants. hZip2 is a member of the ZIP family of eukaryotic metal ion transporters that includes two other human genes, hZIP1 and hZIP3, and genes in mice and rats [5].
  • The supplement had no effect on expression of SLC30A4 or SLC39A1 mRNA [6].
 

Biological context of SLC39A1

 

Anatomical context of SLC39A1

  • Studies of SLC39A1, SLC39A2, and SLC39A4, encoding the proteins hZip1, hZip2, and hZip4, have indicated roles in zinc uptake across the plasma membrane of various cell types [11].
  • After administration of a zinc supplement (22 mg zinc gluconate/d for 27 d), ZIP1 expression decreased by 17% (P < 0.01) and 21% (P < 0.05) in the peripheral leukocytes collected from 15 young (20-25 y) and 10 elderly (64-75 y) subjects, respectively [12].
  • Finally, following overexpression of ZIP1 in MSCs, cDNA microarray analysis revealed differential regulation of several genes associated with the proliferation of osteoprogenitor cells and osteoblast differentiation [3].
  • These changes occur early in malignancy and are sustained during its progression in the peripheral zone. hZIP1 is also expressed in the malignant cell lines LNCaP, PC-3, DU-145; and in the nonmalignant cell lines HPr-1 and BPH-1 [9].
  • The reduction in capacity for accumulation of intracellular zinc in tumorigenic prostate epithelial cells may be caused by the decrease in the ZIP1 protein expression and the intracellular redistribution of ZIP3 in RWPE2 [10].
 

Other interactions of SLC39A1

  • Based on mRNA quantities, Zip1 and ZnT-5 were the most highly expressed [13].
  • Furthermore, we exclude ZIRTL as a JH candidate gene showing that it maps outside the critical interval and that its genomic sequence is normal in three patients [14].
  • Exclusion of ZIRTL as candidate gene of juvenile hemochromatosis and refinement of the critical interval on 1q21 [14].
  • Our results show that hZIP1 overexpression has a functional effect on the malignant potential of prostate cancer cells via inhibition of NF-kappaB-dependent pathways and support the concept that hZIP1 may function as a tumor suppressor gene in prostate cancer [15].

References

  1. The human ZIP1 transporter mediates zinc uptake in human K562 erythroleukemia cells. Gaither, L.A., Eide, D.J. J. Biol. Chem. (2001) [Pubmed]
  2. Prostate cancer in African American men is associated with downregulation of zinc transporters. Rishi, I., Baidouri, H., Abbasi, J.A., Bullard-Dillard, R., Kajdacsy-Balla, A., Pestaner, J.P., Skacel, M., Tubbs, R., Bagasra, O. Appl. Immunohistochem. Mol. Morphol. (2003) [Pubmed]
  3. Overexpression of the ZIP1 zinc transporter induces an osteogenic phenotype in mesenchymal stem cells. Tang, Z., Sahu, S.N., Khadeer, M.A., Bai, G., Franklin, R.B., Gupta, A. Bone (2006) [Pubmed]
  4. Structure, function, and regulation of a subfamily of mouse zinc transporter genes. Dufner-Beattie, J., Langmade, S.J., Wang, F., Eide, D., Andrews, G.K. J. Biol. Chem. (2003) [Pubmed]
  5. Functional expression of the human hZIP2 zinc transporter. Gaither, L.A., Eide, D.J. J. Biol. Chem. (2000) [Pubmed]
  6. Homeostatic regulation of zinc transporters in the human small intestine by dietary zinc supplementation. Cragg, R.A., Phillips, S.R., Piper, J.M., Varma, J.S., Campbell, F.C., Mathers, J.C., Ford, D. Gut (2005) [Pubmed]
  7. Human ZIP1 is a major zinc uptake transporter for the accumulation of zinc in prostate cells. Franklin, R.B., Ma, J., Zou, J., Guan, Z., Kukoyi, B.I., Feng, P., Costello, L.C. J. Inorg. Biochem. (2003) [Pubmed]
  8. Evidence for pH dependent Zn2+influx in K562 erythroleukemia cells: studies using ZnAF-2F fluorescence and 65Zn2+ uptake. Colvin, R.A., Fontaine, C.P., Thomas, D., Hirano, T., Nagano, T., Kikuchi, K. Arch. Biochem. Biophys. (2005) [Pubmed]
  9. hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Franklin, R.B., Feng, P., Milon, B., Desouki, M.M., Singh, K.K., Kajdacsy-Balla, A., Bagasra, O., Costello, L.C. Mol. Cancer (2005) [Pubmed]
  10. Decreased intracellular zinc in human tumorigenic prostate epithelial cells: a possible role in prostate cancer progression. Huang, L., Kirschke, C.P., Zhang, Y. Cancer Cell Int. (2006) [Pubmed]
  11. The SLC39 family of metal ion transporters. Eide, D.J. Pflugers Arch. (2004) [Pubmed]
  12. Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans. Andree, K.B., Kim, J., Kirschke, C.P., Gregg, J.P., Paik, H., Joung, H., Woodhouse, L., King, J.C., Huang, L. J. Nutr. (2004) [Pubmed]
  13. Regulation of zinc metabolism and genomic outcomes. Cousins, R.J., Blanchard, R.K., Moore, J.B., Cui, L., Green, C.L., Liuzzi, J.P., Cao, J., Bobo, J.A. J. Nutr. (2003) [Pubmed]
  14. Exclusion of ZIRTL as candidate gene of juvenile hemochromatosis and refinement of the critical interval on 1q21. Roetto, A., Alberti, F., Daraio, F., Cali, A., Cazzola, M., Totaro, A., Gasparini, P., Camaschella, C. Blood Cells Mol. Dis. (2000) [Pubmed]
  15. Overexpression of the zinc uptake transporter hZIP1 inhibits nuclear factor-kappaB and reduces the malignant potential of prostate cancer cells in vitro and in vivo. Golovine, K., Makhov, P., Uzzo, R.G., Shaw, T., Kunkle, D., Kolenko, V.M. Clin. Cancer Res. (2008) [Pubmed]
 
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