BACKGROUND/AIMS Wilson disease (WD, MIM# 277900) is an autosomal recessive disorder of copper transport resulting from the defective function of a copper transporting P-type ATPase. Detecting mutations and single nucleotide polymorphisms (SNPs) of the ATP7B gene in Turkish pediatric WD patients (n=32) and controls (n=52) is the aim of this research. MATERIALS AND METHODS For screening mutatio...

BACKGROUND Wilson's disease (WD) is a genetic disorder involving the metabolism of copper. WD patients exhibit a wide range of disease phenotypes, including Kayser-Fleischer rings in the cornea, predominant progressive hepatic disease, neurological diseases, and/or psychiatric illnesses, among others. Patients with exon12 mutations of the ATP7B gene have progressive hepatic disease. An ATP7B ge...

Copper is essential for brain metabolism, serving as a cofactor to superoxide dismutase, dopamine-beta-hydroxylase, amyloid precursor protein, ceruloplasmin, and other proteins required for normal brain function. The copper-transporting ATPases ATP7A and ATP7B play a central role in distribution of copper in the central nervous system; genetic mutations in ATP7A and ATP7B lead to severe neurode...

We have previously developed a functional assay in yeast for the copper transporter, ATP7B, defective in Wilson disease (WND). Analysis of WND variant ATP7B proteins revealed that several were able to completely, or nearly completely, complement a mutant yeast strain in which the ATP7B ortholog CCC2 was disrupted, indicating that these ATP7B proteins retained copper transport activity. We analy...

OBJECTIVE To analyze ATP7B mutations in Wilson's disease (WD) patients from the Indian subcontinent and to correlate these with WD phenotype. METHODS We studied 27 WD patients from 25 unrelated families. Twenty-two families were from three southern Indian states - Tamil Nadu andhra Pradesh and Kerala. We applied conformation- sensitive gel electrophoresis (CSGE) to screen for the mutations in...

Previous work has demonstrated that the copper (Cu) transporters Ctr1, Atp7a and Atp7b regulate the cellular pharmacology of cisplatin (CDDP) by mediating its uptake and efflux. It was also shown that, in the process of uptake by Ctr1, CDDP triggers the rapid proteasomal degradation of its own transporter. The current study examined the role of the metallochaperone Atox1 in the regulation of up...

ATP7A and ATP7B are copper-transporting P-type ATPases that are essential to eukaryotic copper homeostasis and must traffic between intracellular compartments to carry out their functions. Previously, we identified a nine-amino acid sequence (F37-E45) in the NH(2) terminus of ATP7B that is required to retain the protein in the Golgi when copper levels are low and target it apically in polarized...

ATP7B is a P-type ATPase involved in copper transport and homeostasis. In experiments with microsomes isolated from COS-1 cells or HepG2 hepatocytes sustaining ATP7B heterologous expression, we found that ATP7B utilization of ATP includes autophosphorylation of an aspartyl residue serving as ATPase catalytic intermediate as well as phosphorylation of serine residues by protein kinase D (PKD). T...

ATP7A and ATP7B are P-type ATPases required for copper homeostasis and involved in the etiology of Menkes and Wilson diseases. We used heterologous expression of ATP7A or ATP7B in COS-1 cells infected with adenovirus vectors to characterize differential features pertinent to each protein expressed in the same mammalian cell type, rather than to extrinsic factors related to different cells susta...