ArticleThe Journal of biological chemistry2015
Communication between the N and C termini is required for copper-stimulated Ser/Thr phosphorylation of Cu(I)-ATPase (ATP7B).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Wilson disease-causing mutations in the carboxyl terminus of ATP7B regulates its localization and Golgi exit selectively in the unpolarized cells.Metallomics : integrated biometal science · 2023Pooled it
- Balancing cellular copper levels via the post-translational regulation of copper transport.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Natural Copper Ion Scavenger: Investigation of the Hepatoprotective Effects of Green Tea Extract in Toxic-Milk Mice with Wilson's Disease Model.Foods (Basel, Switzerland) · 2025Article
- The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B.Frontiers in cellular and infection microbiology · 2023Review
- Structure of the Wilson disease copper transporter ATP7B.Science advances · 2022Article
- Acclimation to Nutritional Immunity and Metal Intoxication Requires Zinc, Manganese, and Copper Homeostasis in the PathogenicFrontiers in cellular and infection microbiology · 2022Review
- Article
- Dynamic and cell-specific transport networks for intracellular copper ions.Journal of cell science · 2021Review
- High dietary copper induces oxidative stress and leads to decreased egg quality and reproductive performance of Chinese Yellow broiler breeder hens.Poultry science · 2021Article
- Copper metabolism as a unique vulnerability in cancer.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Retromer retrieves the Wilson disease protein ATP7B from endolysosomes in a copper-dependent manner.Journal of cell science · 2020Article
- Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties.Scientific reports · 2020Article
- [Progress in molecular mechanism of hepatolenticular degeneration induced by ATP7B gene mutation].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2020Review
- Single nucleotide polymorphisms in the human ATP7B gene modify the properties of the ATP7B protein.Metallomics : integrated biometal science · 2019Article
- A glimpse into the regulation of the Wilson disease protein, ATP7B, sheds light on the complexity of mammalian apical trafficking pathways.Metallomics : integrated biometal science · 2018Review
- The six metal binding domains in human copper transporter, ATP7B: molecular biophysics and disease-causing mutations.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2017Review
- Human copper transporter ATP7B (Wilson disease protein) forms stable dimersThe Journal of biological chemistry · 2017Article
- Regulation of divalent metal transporter-1 by serine phosphorylation.The Biochemical journal · 2016Article
- Copper trafficking to the secretory pathway.Metallomics : integrated biometal science · 2016Review
- Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(-/-) (Wilson disease) mice.Hepatology (Baltimore, Md.) · 2016Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The Wilson disease protein ATP7B exhibits copper-dependent trafficking. In high copper, ATP7B exits the trans-Golgi network and moves to the apical domain of hepatocytes where it facilitates elimination of excess copper through the bile. Copper levels also affect ATP7B phosphorylation. ATP7B is basally phosphorylated in low copper and becomes more phosphorylated ("hyperphosphorylated") in elevated copper. The functional significance of hyperphosphorylation remains unclear. We showed that hyperphosphorylation occurs even when ATP7B is restricted to the trans-Golgi network. We performed comprehensive phosphoproteomics of ATP7B in low versus high copper, which revealed that 24 Ser/Thr residues in ATP7B could be phosphorylated, and only four of these were copper-responsive. Most of the phosphorylated sites were found in the N- and C-terminal cytoplasmic domains. Using truncation and mutagenesis, we showed that inactivation or elimination of all six N-terminal metal binding domains did not block copper-dependent, reversible, apical trafficking but did block hyperphosphorylation in hepatic cells. We showed that nine of 15 Ser/Thr residues in the C-terminal domain were phosphorylated. Inactivation of 13 C-terminal phosphorylation sites reduced basal phosphorylation and eliminated hyperphosphorylation, suggesting that copper binding at the N terminus propagates to the ATP7B C-terminal region. C-terminal mutants with either inactivating or phosphomimetic substitutions showed little effect upon copper-stimulated trafficking, indicating that trafficking does not depend on phosphorylation at these sites. Thus, our studies revealed that copper-dependent conformational changes in the N-terminal region lead to hyperphosphorylation at C-terminal sites, which seem not to affect trafficking and may instead fine-tune copper sequestration.
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