title: Functional characterization of new mutations in Wilson disease gene (ATP7B) using the yeast model.
abstract: The Wilson disease gene, a copper transporting ATPase (Atp7b), is responsible for the sequestration of Cu into secretory vesicles, and this function is exhibited by the orthologous Ccc2p in the yeast. In this study, we aimed to characterize clinically relevant new mutations of human ATP7B (p.T788I, p.V1036I and p.R1038G-fsX83) in yeast lacking the CCC2 gene. Expression of human wild type ATP7B gene in ccc2Δ mutant yeast restored the growth deficiency and copper transport activity; however, expression of the mutant forms did not restore the copper transport functions and only partially supported the cell growth. Our data support that p.T788I, p.V1036I and p.R1038G-fsX83 mutations cause functional deficiency in ATP7B functions and suggest that these residues are important for normal ATP7B function.
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Ozlenen Simsek
authors.initials: OS
authors.lastname: Papur
authors.affiliation: Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey.
authors.forename: Orhan
authors.initials: O
authors.lastname: Terzioglu
authors.affiliation: Department of Molecular Biology and Genetics, Izmir Institute of Technology, 35430 Urla, Izmir, Turkey. Electronic address: ahmetkoc@iyte.edu.tr.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Koc
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D000073840:Copper-Transporting ATPases; D005816:Genetic Complementation Test; D006527:Hepatolenticular Degeneration / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C092974:CCC2 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7B; CCC2; Copper; Saccharomyces cerevisiae; Wilson disease