ArticleThe Journal of biological chemistry2013
Rate and regulation of copper transport by human copper transporter 1 (hCTR1).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 93 citations in OpenAlex.
- 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
- From copper transport to cuproptosis: emerging therapeutic targets in cardiovascular disease.Molecular and cellular biochemistry · 2026Review
- Emerging role of copper in the pathophysiology of spinal cord injury.Neural regeneration research · 2026Article
- Amyloid beta 42 disrupts cardiac function in Alzheimer's disease mice via SLC31A1 upregulation-mediated cuproptosis.Basic research in cardiology · 2026Article
- Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer.Cellular & molecular immunology · 2026Review
- Copper homeostasis and organelle-dependent mechanisms in bone metabolism: implications for osteoporosis therapy.Frontiers in cell and developmental biology · 2026Review
- Human CTR1 Through the Ages: Milestones and Emerging Roles in Disease and Therapy.Biomolecules · 2025Review
- Copper Homeostasis and Cuproptosis As Potential Intervention Strategy in Atherosclerosis.Journal of cardiovascular translational research · 2025Review
- Copper in cancer: friend or foe? Metabolism, dysregulation, and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Exploring the Gating Mechanism of the Human Copper Transporter, hCtr1, Using EPR Spectroscopy.Biomolecules · 2025Article
- Clinical and molecular characterization of SLC31A1-related developmental and epileptic encephalopathy: insights from 13 new cases.Brain communications · 2025Article
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Molecular insights into substrate translocation in an elevator-type metal transporter.Nature communications · 2024Article
- Blocking lactate regulation of the Grhl2/SLC31A1 axis inhibits trophoblast cuproptosis and preeclampsia development.Journal of assisted reproduction and genetics · 2024Article
- Molecular insights into substrate translocation in an elevator-type metal transporter.bioRxiv : the preprint server for biology · 2024Article
- Determination of metal ion transport rate of human ZIP4 using stable zinc isotopes.The Journal of biological chemistry · 2024Article
- The interplay of transition metals in ferroptosis and pyroptosis.Cell division · 2024Review
- A Systematic Genotoxicity Assessment of a Suite of Metal Oxide Nanoparticles Reveals Their DNA Damaging and Clastogenic Potential.Nanomaterials (Basel, Switzerland) · 2024Article
- Copper Homeostasis in the Model OrganismCells · 2024Review
- Comprehensive analysis of the effects of the cuprotosis-associated geneTranslational cancer research · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Human copper transporter 1 (hCTR1) is a homotrimer of a 190-amino acid monomer having three transmembrane domains believed to form a pore for copper permeation through the plasma membrane. The hCTR1-mediated copper transport mechanism is not well understood, nor has any measurement been made of the rate at which copper ions are transported by hCTR1. In this study, we estimated the rate of copper transport by the hCTR1 trimer in cultured cells using (64)Cu uptake assays and quantification of plasma membrane hCTR1. For endogenous hCTR1, we estimated a turnover number of about 10 ions/trimer/s. When overexpressed in HEK293 cells, a second transmembrane domain mutant of hCTR1 (H139R) had a 3-fold higher Km value and a 4-fold higher turnover number than WT. Truncations of the intracellular C-terminal tail and an AAA substitution of the putative metal-binding HCH C-terminal tripeptide (thought to be required for transport) also exhibited elevated transport rates and Km values when compared with WT hCTR1. Unlike WT hCTR1, H139R and the C-terminal mutants did not undergo regulatory endocytosis in elevated copper. hCTR1 mutants combining methionine substitutions that block transport (M150L,M154L) on the extracellular side of the pore and the high transport H139R or AAA intracellular side mutations exhibited the blocked transport of M150L,M154L, confirming that Cu(+) first interacts with the methionines during permeation. Our results show that hCTR1 elements on the intracellular side of the hCTR1 pore, including the carboxyl tail, are not essential for permeation, but serve to regulate the rate of copper entry.
Indexed as
Identifiers
What OpenQuestion holds
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.