ArticleThe Journal of biological chemistry2009
Human copper transporter 1 lacking O-linked glycosylation is proteolytically cleaved in a Rab9-positive endosomal compartment.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Cu(I) and Cu(II) binding by hyperactive variants of the human CTR1 N-terminus: Insights from cellular and model peptide studies.Journal of inorganic biochemistry · 2026Article
- 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
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- SLC31A1 Identifying a Novel Biomarker with Potential Prognostic and Immunotherapeutic Potential in Pan-Cancer.Biomedicines · 2023Article
- Crossroads between membrane trafficking machinery and copper homeostasis in the nerve system.Open biology · 2021Review
- Copper trafficking in eukaryotic systems: current knowledge from experimental and computational efforts.Current opinion in structural biology · 2019Review
- Copper transporters and copper chaperones: roles in cardiovascular physiology and disease.American journal of physiology. Cell physiology · 2018Review
- Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2.The Journal of biological chemistry · 2017Article
- Cathepsin Protease Controls Copper and Cisplatin Accumulation via Cleavage of the Ctr1 Metal-binding Ectodomain.The Journal of biological chemistry · 2016Article
- Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus.The Journal of biological chemistry · 2016Article
- How copper traverses cellular membranes through the mammalian copper transporter 1, Ctr1.Annals of the New York Academy of Sciences · 2014Article
- Characterization of a monoclonal antibody capable of reliably quantifying expression of human Copper Transporter 1 (hCTR1).Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2014Article
- Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- A role for the copper transporter Ctr1 in the synergistic interaction between hyperthermia and cisplatin treatment.International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group · 2013Article
- Rate and regulation of copper transport by human copper transporter 1 (hCTR1).The Journal of biological chemistry · 2013Article
- A sensor of protein O-glycosylation based on sequential processing in the Golgi apparatus.Traffic (Copenhagen, Denmark) · 2013Article
- Polymorphic transporters and platinum pharmacodynamics.Drug metabolism and pharmacokinetics · 2013Review
- Model peptides provide new insights into the role of histidine residues as potential ligands in human cellular copper acquisition via Ctr1.Journal of the American Chemical Society · 2011Article
- Ctr1 is an apical copper transporter in mammalian intestinal epithelial cells in vivo that is controlled at the level of protein stability.The Journal of biological chemistry · 2010Article
- Copper transporters and the cellular pharmacology of the platinum-containing cancer drugs.Molecular pharmacology · 2010Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The human copper transporter hCTR1 is a homotrimer composed of a plasma membrane protein of 190 amino acids that contains three transmembrane segments. The extracellular 65-amino acid amino terminus of hCTR1 contains both N-linked (at Asn(15)) and O-linked (at Thr(27)) sites of glycosylation. If O-glycosylation at Thr(27) is prevented, hCTR1 is efficiently cleaved, removing approximately 30 amino acids from the amino terminus. We have now investigated (i) the site of this cleavage, determining which peptide bonds are cleaved, (ii) the mechanism by which glycosylation prevents cleavage, and (iii) where in the cell the proteolytic cleavage takes place. Cleavage occurs in the sequence Ala-Ser-His-Ser-His (residues 29-33), which does not contain previously recognized protease cleavage sites. Using a series of hCTR1 mutants, we show that cleavage occurs preferentially between residues Ala(29)-Ser(30)-His(31). We also show that the O-linked polysaccharide at Thr(27) blocks proteolysis due to its proximity to the cleavage site. Moving the cleavage site away from the Thr(27) polysaccharide by insertion of as few as 5 amino acids allows cleavage to occur in the presence of glycosylation. Imaging studies using immunofluorescence in fixed cells and a functional green fluorescent protein-tagged hCTR1 transporter in live cells showed that the cleaved peptide accumulates in punctate structures in the cytoplasm. These puncta overlap compartments were stained by Rab9, indicating that hCTR1 cleavage occurs in a late endosomal compartment prior to delivery of the transporter to the plasma membrane.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.