ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
Apical targeting and Golgi retention signals reside within a 9-amino acid sequence in the copper-ATPase, ATP7B.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 88 citations in OpenAlex.
- Clinical Exome Sequencing in Unexplained Hyperferritinemia Reveals Digenic and Oligogenic Inheritance Beyond Iron Homeostasis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- The interactions of copper, glutamate, and cuproptosis: insights into brain health and Alzheimer's disease pathology.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- TRIM14 Regulation of Copper Homeostasis and Cuproptosis: A New Strategy to Overcome Chemoresistance in Glioblastoma.Biomedicines · 2025Article
- Novel and less invasive biomarker assays to measure liver ATP7B in Wilson disease patients.Scientific reports · 2025Article
- Progress in Research on Regulated Cell Death in Cerebral Ischaemic Injury After Cardiac Arrest.Journal of cellular and molecular medicine · 2025Review
- Functional Screen of Wilson Disease ATP7B Variants Reveals Residual Transport Activities.Human mutation · 2025Article
- The physiological and pathophysiological roles of copper in the nervous system.The European journal of neuroscience · 2024Review
- Regulation of the apico-basolateral trafficking polarity of the homologous copper-ATPases ATP7A and ATP7B.Journal of cell science · 2024Article
- Copper in the colorectal cancer microenvironment: pioneering a new era of cuproptosis-based therapy.Frontiers in oncology · 2024Review
- Abnormalities in Copper Status Associated with an Elevated Risk of Parkinson's Phenotype Development.Antioxidants (Basel, Switzerland) · 2023Review
- Copper binding leads to increased dynamics in the regulatory N-terminal domain of full-length human copper transporter ATP7B.PLoS computational biology · 2022Article
- Review
- At sixes and sevens: cryptic domain in the metal binding chain of the human copper transporter ATP7A.Biophysical journal · 2021Article
- Review
- 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
- [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
- ATP7B Binds Ruthenium(II)Inorganic chemistry · 2019Article
- Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
ATP7B is a copper-transporting P-type ATPase present predominantly in liver. In basal copper, hepatic ATP7B is in a post-trans-Golgi network (TGN) compartment where it loads cytoplasmic Cu(I) onto newly synthesized ceruloplasmin. When copper levels rise, the protein redistributes via unique vesicles to the apical periphery where it exports intracellular Cu(I) into bile. We want to understand the mechanisms regulating the copper-sensitive trafficking of ATP7B. Earlier, our laboratory reported the presence of apical targeting/TGN retention information within residues 1-63 of human ATP7B; deletion of these residues resulted in a mutant protein that was not efficiently retained in the post-TGN in low copper and constitutively trafficked to the basolateral membrane of polarized, hepatic WIF-B cells with and without copper (13). In this study, we used mutagenesis and adenovirus infection of WIF-B cells followed by confocal immunofluorescence microscopy analysis to identify the precise retention/targeting sequences in the context of full-length ATP7B. We also analyzed the expression of selected mutants in livers of copper-deficient and -loaded mice. Our combined results clearly demonstrate that nine amino acids, F(37)AFDNVGYE(45), comprise an essential apical targeting determinant for ATP7B in elevated copper and participate in the TGN retention of the protein under low-copper conditions. The signal is novel, does not require phosphorylation, and is highly conserved in approximately 24 species of ATP7B. Furthermore, N41S, which is part of the signal we identified, is the first and only Wilson disease-causing missense mutation in residues 1-63 of ATP7B. Expression of N41S-ATP7B in WIF-B cells severely disabled the targeting and retention of the protein. We present a working model of how this physiologically relevant signal might work.
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