TY - JOUR
T1 - Intracellular pathways of copper trafficking in yeast and humans
AU - Culotta, Valeria Cizewski
AU - Lin, Su Ju
AU - Schmidt, Paul
AU - Klomp, Leo W.J.
AU - Casareno, Ruby Leah B.
AU - Gitlin, Jonathan
PY - 1999
Y1 - 1999
N2 - In the bakers yeast S. cerevisiae, there at least four intracellular targets requiring copper ions- 1) Ccc2p and Fet3p in the secretory pathway (homologues to Menkes/Wilson proteins and ceruloplasmin); 2) cytochrome oxidase in the mitochondria; 3) copper transcription factors in the nucleus; and 4) Cu/Zn superoxide dismutase (SOD1) in the cytosol. We have discovered a small soluble copper carrier that specifically delivers copper ions to the secretory pathway. This 8.2 kDa factor known as Atx1p, exhibits striking homology to the MERp mercury carrier of bacteria and contains a single MTCXXC metal binding site also found in the Menkes/Wilson family of copper transporting ATPases: Our studies show that Atx1p is cytosolic and facilitates the delivery of copper ions from the cell surface copper transporter to Ccc2p and Fet3p in the secretory pathway; furthermore, it is not involved in the delivery of copper ions to the mitochondria, the nucleus or cytosolic SOD1, implicating specific signals directing Atx1p to the secretory pathway. Homologues to Atx1p have been found in invertebrates, plants and humans, and the human gene is abundantly expressed in all tissues. In addition to Atx1p, we have recently uncovered an additional metal trafficking protein that appears to specifically deliver copper ions to SOD1. Mutants in the corresponding gene (lys7) are defective for SOD1 activity, and are unable to incorporate copper into SOD1, while there is no obvious impairment in copper delivery to cytochrome oxidase or Fet3p. The encoded 27 kDa protein contains a single MHCXXC consensus copper binding sequence and close homologues have been identified in a wide array of eukaryotic species including humans.
AB - In the bakers yeast S. cerevisiae, there at least four intracellular targets requiring copper ions- 1) Ccc2p and Fet3p in the secretory pathway (homologues to Menkes/Wilson proteins and ceruloplasmin); 2) cytochrome oxidase in the mitochondria; 3) copper transcription factors in the nucleus; and 4) Cu/Zn superoxide dismutase (SOD1) in the cytosol. We have discovered a small soluble copper carrier that specifically delivers copper ions to the secretory pathway. This 8.2 kDa factor known as Atx1p, exhibits striking homology to the MERp mercury carrier of bacteria and contains a single MTCXXC metal binding site also found in the Menkes/Wilson family of copper transporting ATPases: Our studies show that Atx1p is cytosolic and facilitates the delivery of copper ions from the cell surface copper transporter to Ccc2p and Fet3p in the secretory pathway; furthermore, it is not involved in the delivery of copper ions to the mitochondria, the nucleus or cytosolic SOD1, implicating specific signals directing Atx1p to the secretory pathway. Homologues to Atx1p have been found in invertebrates, plants and humans, and the human gene is abundantly expressed in all tissues. In addition to Atx1p, we have recently uncovered an additional metal trafficking protein that appears to specifically deliver copper ions to SOD1. Mutants in the corresponding gene (lys7) are defective for SOD1 activity, and are unable to incorporate copper into SOD1, while there is no obvious impairment in copper delivery to cytochrome oxidase or Fet3p. The encoded 27 kDa protein contains a single MHCXXC consensus copper binding sequence and close homologues have been identified in a wide array of eukaryotic species including humans.
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U2 - 10.1007/978-1-4615-4859-1_22
DO - 10.1007/978-1-4615-4859-1_22
M3 - Article
C2 - 10079832
AN - SCOPUS:0033278379
SN - 0065-2598
VL - 448
SP - 247
EP - 254
JO - Advances in experimental medicine and biology
JF - Advances in experimental medicine and biology
ER -