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MIM.603864 11q13

Sunday 20 April 2008

Copper (Cu) is required for aerobic life and yet, paradoxically, is highly toxic. This apparent contradiction has been rationalized by assuming that Cu, like other redox-active metals, is sequestered in nonreactive forms as it is transported into cells and moves through cellular compartments.

One such Cu chaperone protein, Lys7, specifically delivers Cu to copper/zinc superoxide dismutase (Sod1) (MIM.147450) in S. cerevisiae. The human Lys7 homolog has been named CCS (copper chaperone for SOD1). The predicted 274-amino acid human protein is 28% identical to Lys7.

CCS complemented a yeast Lys7 mutation, demonstrating that CCS is a functional homolog of Lys7. Northern blot analysis revealed that CCS was expressed as a 1.2-kb mRNA in all tissues and cell lines tested. 30 PubMed Neighbors

The region of CCS encompassing amino acids 86-234 shares 47% identity with human SOD1. The residues of SOD1 identical to those of CCS include all of the known Cu and zinc ligands, the dimerization interface, and most of the amino acid residues mutated in familial ALS (MIM.105400).

Binding assays and coimmunoprecipitation studies indicated that SOD1 and CCS directly interact in vitro and in vivo via the homologous domains in each protein.

Immunofluorescence analysis experiments showed that CCS and SOD1 were distributed in an identical pattern throughout the cytoplasm and nucleus of mammalian cells. Cu delivery to SOD1 is mediated via a direct interaction with CCS.