Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces cerevisiae.

Wilson disease is a genetic disorder of copper metabolism characterized by the toxic accumulation of copper in the liver. The ATP7B gene, which encodes a copper transporting P-type ATPase, is defective in patients with Wilson disease. To investigate the function of ATP7B, wild type or mutated ATP7B cDNA was introduced into a yeast strain lacking the CCC2 gene (delta ccc2), the yeast homologue of ATP7B. Wild type and the H1069Q mutant could rescue delta ccc2, however, the N1270S mutant could not, reflecting phenotypic variability of Wilson disease. In addition, the mutant containing only the sixth copper binding domain could rescue delta ccc2, indicating its functional importance.