GO:1902311 regulation of copper ion transmembrane transport: Transport Regulation, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1902311 describes any process that modulates the frequency, rate or extent of copper ion transmembrane transport, a critical homeostatic control point for copper-dependent enzymes and signaling.
• Copper transport is mediated by high-affinity transporters such as CTR1 (SLC31A1) and copper-transporting P-type ATPases (ATP7A/ATP7B), whose activity is tightly regulated at the membrane.
• Dysregulation of copper ion transmembrane transport is linked to Wilson disease, cancer, inflammatory bowel disease, and cardiovascular risk.
• CRISPR/Cas9 knockout of CTR1 and DMT1 in NSCLC cells alters copper homeostasis and drug sensitivity, demonstrating the power of gene editing to dissect this process.
• Regulation occurs at multiple levels: transcriptional control, protein trafficking, metal-binding domain interactions, and redox-dependent modulation of transport activity.
• Studying GO:1902311 requires integrated approaches including transport assays, live-cell imaging, and CRISPR-based perturbation of key transporters.
Description
Copper is an essential trace element required for the activity of enzymes involved in respiration, antioxidant defense, and neurotransmitter synthesis, but free copper is toxic, so cells must tightly regulate its transmembrane movement. The Gene Ontology term GO:1902311, regulation of copper ion transmembrane transport, captures any process that modulates the frequency, rate or extent of copper ion transmembrane transport, encompassing both the transport machinery and its upstream regulators. This term is central to understanding how cells balance copper uptake, distribution, and efflux to avoid deficiency or overload. Researchers study GO:1902311 because its disruption underlies diseases such as Wilson disease, where mutations in the copper-transporting ATPase ATP7B impair biliary copper excretion, and because cancer cells often reprogram copper transport to support proliferation and drug resistance. Moreover, copper transport regulation influences inflammatory bowel disease and myocardial infarction risk, highlighting its broad physiological relevance. The term is defined as any process that modulates the frequency, rate or extent of copper ion transmembrane transport, and it includes both positive and negative regulation of transporters like CTR1 and ATP7A/ATP7B.
regulation of copper ion transmembrane transport At A Glance
| GO ID | GO:1902311 |
|---|---|
| GO term | regulation of copper ion transmembrane transport |
| Ontology | biological_process |
| Synonym | regulation of copper cation transmembrane transport; regulation of copper ion membrane transport |
| Major function | Modulates the frequency, rate or extent of copper ion transmembrane transport |
| Related transporters | CTR1 (SLC31A1), ATP7A, ATP7B, DMT1 |
| Disease relevance | Wilson disease, cancer, inflammatory bowel disease, cardiovascular risk |
| Research methods | CRISPR knockout, transport assays, live-cell imaging, proteomics |
What Is GO:1902311?
GO:1902311, regulation of copper ion transmembrane transport, is a biological process defined as any process that modulates the frequency, rate or extent of copper ion transmembrane transport. In practice, this includes changes in the activity, localization, or abundance of copper transporters such as CTR1, ATP7A, and ATP7B, as well as signals that alter their capacity to move copper across membranes. The term is not the transport itself but the regulatory inputs that set the rate and direction of copper flux.
Why Is regulation of copper ion transmembrane transport Important in Cell Biology?
Regulation of copper ion transmembrane transport is essential because copper is both indispensable and toxic, and its misregulation contributes to a wide range of human diseases. The term GO:1902311 provides a framework for understanding how cells adjust copper uptake and efflux in response to metabolic needs, stress, and disease states. For example, the copper-transporting P-type ATPases ATP7A and ATP7B are regulated by metal-binding domains and trafficking signals that control their transport activity and localization. In cancer, high-affinity copper transporter 1 (CTR1) is often dysregulated, affecting platinum-based drug uptake and sensitivity. In inflammatory bowel disease, glutaredoxin 1 promotes copper toxicity in intestinal epithelial cells, implicating transport regulation in tissue damage. Thus, studying GO:1902311 is critical for developing therapies that target copper homeostasis.
• Copper is a cofactor for cytochrome c oxidase, superoxide dismutase, and ceruloplasmin, so its transport regulation is vital for energy metabolism and antioxidant defense.
• Mutations in ATP7B cause Wilson disease, a disorder of copper overload, directly linking GO:1902311 to human pathology.
• CTR1-mediated copper transport also affects cisplatin uptake, making its regulation relevant to cancer chemotherapy.
• CRISPR/Cas9 deletion of CTR1 and DMT1 in NSCLC cells alters copper homeostasis and pharmacological responses, showing the importance of transport regulation in cancer.
• In Pseudomonas aeruginosa, disruption of transmembrane copper transport triggers periplasmic responses, indicating that regulation is conserved in bacteria.
• Glutaredoxin 1 promotes intestinal epithelial copper toxicity in inflammatory bowel disease, highlighting redox regulation of copper transport.
• Electrochemical regulation of mitochondrial respiratory chain redox states using transmembrane copper peptides is being explored for myocardial infarction risk assessment.
• Understanding GO:1902311 can guide the development of copper-targeting therapeutics for cancer, neurodegeneration, and metabolic disorders.
• Regulation of copper transport is achieved through metal-binding domains, phosphorylation, and protein trafficking, offering multiple druggable nodes.
• The term integrates signals from copper availability, oxidative stress, and cellular demand, making it a hub for systems-level studies.
What Happens During regulation of copper ion transmembrane transport?
Copper uptake and CTR1 regulation
In simple terms: Cells take in copper through a dedicated transporter called CTR1, and the cell controls how much copper enters by adjusting CTR1 activity and location.
High-affinity copper transporter 1 (CTR1, SLC31A1) is the primary mediator of copper uptake in mammalian cells. Its transport rate is regulated by extracellular copper levels, which can trigger endocytosis and degradation of CTR1, thereby reducing further uptake. Mechanistic studies show that CTR1 also transports cisplatin, and its regulation affects drug sensitivity. In NSCLC cells, CRISPR/Cas9-mediated deletion of CTR1 alters copper homeostasis and biological responses, confirming its central role in copper ion transmembrane transport.
Copper efflux and P-type ATPase regulation
In simple terms: When copper levels are too high, cells use pumps called ATP7A and ATP7B to move copper out or into storage compartments, and these pumps are regulated by copper binding and trafficking.
Copper-transporting P-type ATPases, ATP7A and ATP7B, mediate copper efflux and sequestration. Their activity is regulated by cytosolic metal-binding domains that sense copper and modulate catalytic cycles. In Wilson disease, mutations in ATP7B impair biliary copper excretion, leading to hepatic and neurological copper accumulation. The regulation of these ATPases involves copper-dependent trafficking between the trans-Golgi network and the plasma membrane, a key aspect of GO:1902311.
Redox-dependent modulation of copper transport
In simple terms: The oxidative state of the cell can change how copper transporters work, because copper ions can be oxidized or reduced, affecting their handling.
Glutaredoxin 1 (Grx1) promotes intestinal epithelial cell copper toxicity in inflammatory bowel disease, indicating that redox regulation intersects with copper transport. In Pseudomonas aeruginosa, disruption of transmembrane copper transport induces periplasmic responses, suggesting that bacteria sense and respond to copper transport status. These findings highlight that regulation of copper ion transmembrane transport is not solely about transporter abundance but also about redox environment and stress signaling.
Mitochondrial copper transport and respiratory chain regulation
In simple terms: Copper is needed inside mitochondria for energy production, and its transport across mitochondrial membranes is regulated to maintain respiratory chain function.
Electrochemical regulation of mitochondrial respiratory chain protein redox states using transmembrane copper peptides has been explored for myocardial infarction risk assessment, linking copper transport regulation to mitochondrial function. This suggests that regulation of copper ion transmembrane transport extends to intracellular organelles, where copper availability influences oxidative phosphorylation and redox balance.
Integration of regulatory signals
In simple terms: Cells integrate multiple signals, such as copper levels, oxidative stress, and metabolic demand, to fine-tune copper transport across membranes.
The regulation of copper ion transmembrane transport involves cross-talk between transcriptional programs, protein trafficking, and post-translational modifications. For example, metal-binding domains in ATP7A/ATP7B act as sensors that adjust transport activity in response to copper. CTR1 regulation by copper-induced endocytosis provides a rapid feedback mechanism. Together, these layers ensure that copper flux matches cellular needs while preventing toxicity.
Key Genes Involved in GO:1902311 regulation of copper ion transmembrane transport
The following genes and proteins are central to the regulation of copper ion transmembrane transport, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC31A1 (CTR1) | High-affinity copper uptake transporter | Regulated by copper-induced endocytosis; target for cancer drug sensitivity studies |
| ATP7A | Copper efflux pump; Menkes disease gene | Regulated by metal-binding domains and trafficking; studied in copper homeostasis |
| ATP7B | Copper efflux pump; Wilson disease gene | Mutations cause copper overload; key for Wilson disease research |
| DMT1 (SLC11A2) | Divalent metal transporter; also transports copper | CRISPR deletion in NSCLC alters copper homeostasis |
| GLRX1 (Glutaredoxin 1) | Redox regulator; promotes copper toxicity | Implicated in inflammatory bowel disease copper toxicity |
| COX1 (MT-CO1) | Mitochondrial cytochrome c oxidase subunit; copper-dependent | Mitochondrial copper transport affects respiratory chain |
| SOD1 | Copper-zinc superoxide dismutase | Copper delivery to SOD1 depends on transport regulation |
| CP (Ceruloplasmin) | Copper-binding ferroxidase | Copper loading requires transport regulation |
| ATOX1 | Copper chaperone for ATP7A/ATP7B | Delivers copper to P-type ATPases; part of regulatory network |
| CCS | Copper chaperone for SOD1 | Facilitates copper insertion into SOD1 |
| MT1A (Metallothionein) | Copper-binding protein | Buffers copper and influences transport regulation |
| COMMD1 | Copper metabolism regulator | Interacts with ATP7B; affects copper excretion |
| XIAP | Inhibitor of apoptosis; copper-binding | May modulate copper transport under stress |
| PARK7 (DJ-1) | Oxidative stress sensor; copper-binding | Links copper transport to neurodegeneration |
| SLC25A3 | Mitochondrial phosphate carrier; copper-related | Mitochondrial copper transport affects energy metabolism |
| COX17 | Copper chaperone for cytochrome c oxidase | Delivers copper to mitochondria; regulated by transport |
| SCO1 | Copper chaperone for COX assembly | Mitochondrial copper transport regulation |
| ATP7B variants | Mutant forms affecting transport | Studied in Wilson disease models |
How Is regulation of copper ion transmembrane transport Regulated?
Regulation of copper ion transmembrane transport is achieved through multiple mechanisms. CTR1 is regulated by copper-dependent endocytosis and degradation, which reduces uptake when copper is abundant. ATP7A and ATP7B are regulated by their cytosolic metal-binding domains, which sense copper and modulate catalytic activity, and by copper-induced trafficking between intracellular compartments and the plasma membrane. Redox state also plays a role; glutaredoxin 1 promotes copper toxicity in intestinal epithelial cells, suggesting that redox signals can enhance or impair transport regulation. In bacteria, disruption of transmembrane copper transport triggers periplasmic responses, indicating a feedback regulatory loop. Additionally, mitochondrial copper transport is regulated to maintain respiratory chain function, as shown by electrochemical modulation using transmembrane copper peptides.
regulation of copper ion transmembrane transport and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ATP7B | Wilson disease (copper overload) | ATP7B knockout or point-mutation hepatocyte cell lines |
| SLC31A1 (CTR1) | Cancer drug sensitivity (cisplatin) | CRISPR knockout in NSCLC H1299 cells |
| GLRX1 | Inflammatory bowel disease copper toxicity | Intestinal epithelial cell lines with GLRX1 knockout or overexpression |
| DMT1 (SLC11A2) | Copper homeostasis in cancer | CRISPR knockout in NSCLC H1299 cells |
| Mitochondrial copper transporters | Myocardial infarction risk | Cardiomyocyte models with transmembrane copper peptide treatment |
Wilson disease and copper overload
Wilson disease is an autosomal recessive disorder caused by mutations in ATP7B, a copper-transporting P-type ATPase. Defective ATP7B leads to impaired biliary copper excretion and reduced incorporation of copper into ceruloplasmin, resulting in copper accumulation in the liver, brain, and other organs. The regulation of copper ion transmembrane transport is therefore central to Wilson disease pathogenesis, and experimental models often use ATP7B knockout or point-mutation cell lines to study transport defects.
Cancer and copper transport dysregulation
Cancer cells often reprogram copper homeostasis to support proliferation and survival. CTR1 (SLC31A1) mediates copper uptake and also transports cisplatin, so its regulation affects chemotherapy response. CRISPR/Cas9-mediated deletion of CTR1 and DMT1 in NSCLC cell line H1299 alters copper homeostasis and pharmacological sensitivity, demonstrating that copper transport regulation is a potential therapeutic target in cancer. Dysregulated copper transport may also contribute to resistance to platinum-based drugs.
Inflammatory bowel disease and copper toxicity
In inflammatory bowel disease, glutaredoxin 1 promotes intestinal epithelial cell copper toxicity, linking redox regulation of copper transport to tissue damage. This suggests that modulating copper ion transmembrane transport could be a strategy to reduce epithelial injury in inflammatory conditions.
Cardiovascular risk and mitochondrial copper
Electrochemical regulation of mitochondrial respiratory chain protein redox states using transmembrane copper peptides has been investigated for myocardial infarction risk assessment, indicating that copper transport regulation influences cardiac mitochondrial function and cardiovascular risk. This emerging area highlights the importance of GO:1902311 beyond classical copper metabolism disorders.
From regulation of copper ion transmembrane transport-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of CTR1 alter copper uptake and drug sensitivity? | CRISPR knockout of SLC31A1 in cancer cell lines |
| How do ATP7B mutations affect copper efflux? | Point-mutation knock-in of ATP7B variants in hepatocyte-like cells |
| Can copper transport be monitored in real time? | Tagged knock-in of CTR1 or ATP7B with fluorescent tags |
| Does overexpression of glutaredoxin 1 enhance copper toxicity? | Overexpression of GLRX1 in intestinal epithelial cells |
| What is the role of mitochondrial copper transport in respiration? | Knockout of COX17 or SCO1 in cardiomyocytes |
| How does bacterial copper transport disruption affect periplasm? | Knockout of copper transport genes in Pseudomonas aeruginosa |
How to Study the regulation of copper ion transmembrane transport Process
| Method | What It Measures | Typical Application |
|---|---|---|
| 64Cu uptake/efflux assay | Rate of copper transport across membranes | CTR1 and ATP7B functional studies |
| Live-cell fluorescence imaging | Transporter localization and trafficking | Copper-induced endocytosis of CTR1 |
| CRISPR/Cas9 knockout | Gene function in copper transport | CTR1 and DMT1 deletion in NSCLC |
| Site-directed mutagenesis | Effect of point mutations on transport | ATP7B variants in Wilson disease |
| Proteomics | Protein expression and redox modifications | Mitochondrial copper peptide effects |
| Redox assays (e.g., GSH/GSSG) | Oxidative stress status | Glutaredoxin 1-mediated copper toxicity |
| Bacterial periplasmic fractionation | Periplasmic response to copper transport disruption | Pseudomonas aeruginosa studies |
| Electrochemical sensing | Redox states of respiratory chain proteins | Myocardial infarction risk assessment |
Transport assays with radioactive or fluorescent copper
Copper transport rates can be measured using radioactive 64Cu or fluorescent copper sensors in live cells. These assays quantify uptake and efflux and are used to study CTR1 and ATP7A/ATP7B regulation. For example, mechanistic comparisons of CTR1-mediated transport between copper and cisplatin rely on such assays.
Live-cell imaging of transporter trafficking
Fluorescently tagged transporters (e.g., GFP-CTR1, GFP-ATP7B) allow visualization of copper-induced trafficking and localization changes. This approach reveals how regulation of copper ion transmembrane transport involves dynamic relocalization of transporters.
CRISPR/Cas9 gene editing to dissect transport regulation
CRISPR knockout of CTR1 and DMT1 in NSCLC cells has been used to study biological and pharmacological consequences of disrupted copper transport. Point mutations can be introduced to model disease variants, such as ATP7B mutations in Wilson disease.
Proteomics and redox state analysis
Proteomic profiling and redox state measurements can identify changes in mitochondrial respiratory chain proteins upon modulation of copper transport, as demonstrated with transmembrane copper peptides. Glutaredoxin 1-dependent copper toxicity can be assessed by redox assays in intestinal epithelial cells.
How CRISPR Can Be Used to Study GO:1902311 regulation of copper ion transmembrane transport
Knockout
CRISPR/Cas9 knockout is used to delete copper transport genes such as SLC31A1 (CTR1) and SLC11A2 (DMT1) to study their roles in copper homeostasis and drug sensitivity. For example, deletion of CTR1 and DMT1 in NSCLC H1299 cells altered biological and pharmacological responses, demonstrating the utility of knockout models for GO:1902311 research.
Point Mutation
Point mutations can be introduced to model disease-associated variants, such as ATP7B mutations in Wilson disease, to study their impact on copper transport regulation. CRISPR-based base editing or homology-directed repair enables precise mutation of residues in metal-binding domains or catalytic sites.
Knock-in
Knock-in of tagged transporters (e.g., GFP or HA tags) allows real-time tracking of protein localization and trafficking under different copper conditions, providing insights into regulation of copper ion transmembrane transport. Knock-in of disease variants can also create isogenic models for drug testing.
Overexpression
Overexpression of copper transport regulators such as glutaredoxin 1 (GLRX1) can enhance copper toxicity in intestinal epithelial cells, modeling inflammatory bowel disease aspects. Overexpression of CTR1 or ATP7B can be used to study gain-of-function effects on copper flux and cellular sensitivity.
How EDITGENE Supports regulation of copper ion transmembrane transport Research
Researchers studying regulation of copper ion transmembrane transport-related genes often need to determine whether a candidate gene is causally involved in copper homeostasis, disease progression, or drug response. EDITGENE provides comprehensive CRISPR-based services to generate precisely engineered cell models, enabling functional validation of genes implicated in GO:1902311.
Contact EDITGENE today to design your custom CRISPR model for regulation of copper ion transmembrane transport research.
Frequently Asked Questions About regulation of copper ion transmembrane transport
What is GO:1902311?
GO:1902311 is the Gene Ontology term for regulation of copper ion transmembrane transport, defined as any process that modulates the frequency, rate or extent of copper ion transmembrane transport.
What genes are involved in regulation of copper ion transmembrane transport?
Key genes include SLC31A1 (CTR1), ATP7A, ATP7B, DMT1, and GLRX1, which mediate or regulate copper movement across membranes.
How is copper ion transmembrane transport regulated?
It is regulated by copper-dependent endocytosis of CTR1, metal-binding domain sensing in ATP7A/ATP7B, redox signals, and transcriptional programs.
What diseases are linked to copper transport dysregulation?
Wilson disease, cancer, inflammatory bowel disease, and cardiovascular risk are associated with altered copper ion transmembrane transport.
How can CRISPR be used to study copper transport?
CRISPR knockout, point mutation, knock-in, and overexpression models allow functional dissection of copper transport genes and their regulators.
What methods measure copper transport regulation?
Radioactive copper uptake assays, live-cell imaging, proteomics, and redox assays are commonly used.
Why is copper transport regulation important for cancer?
CTR1 regulates uptake of copper and cisplatin, affecting drug sensitivity; its deletion alters cancer cell responses.
What is the role of ATP7B in copper transport?
ATP7B is a copper-transporting P-type ATPase that mediates biliary copper excretion; its mutations cause Wilson disease.
Can copper transport be targeted therapeutically?
Yes, modulating copper transport is being explored for cancer, Wilson disease, and inflammatory conditions.
What model systems are used to study GO:1902311?
Cell lines with CRISPR edits, bacterial models, and mitochondrial preparations are used to study copper transport regulation.
Conclusion
GO:1902311, regulation of copper ion transmembrane transport, is a fundamental biological process that controls copper homeostasis and prevents toxicity. Its dysregulation is implicated in Wilson disease, cancer, inflammatory bowel disease, and cardiovascular risk, making it a critical area of research. Advances in CRISPR gene editing and transport assays continue to unravel the complex regulatory networks involving CTR1, ATP7A, ATP7B, and redox modulators. Understanding these mechanisms will inform therapeutic strategies targeting copper transport in human disease.
References
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- 2. Maryon EB et al.. 2013. Rate and regulation of copper transport by human copper transporter 1 (hCTR1).. J Biol Chem 288(25):18035-46 PMID: 23658018
- 3. Guo Z et al.. 2024. Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases.. Nat Commun 15(1):2690 PMID: 38538615
- 4. Hao P et al.. 2026. Electrochemical regulation of mitochondrial respiratory chain protein redox states using transmembrane copper peptides for myocardial infarction risk assessment.. Bioelectrochemistry 167:109071 PMID: 40815886
- 5. Raimunda D et al.. 2013. Periplasmic response upon disruption of transmembrane Cu transport in Pseudomonas aeruginosa.. Metallomics 5(2):144-51 PMID: 23354150
- 6. Liang ZD et al.. 2009. Mechanistic comparison of human high-affinity copper transporter 1-mediated transport between copper ion and cisplatin.. Mol Pharmacol 76(4):843-53 PMID: 19570948
- 7. Ilyechova EY et al.. 2019. CRISP-R/Cas9 Mediated Deletion of Copper Transport Genes CTR1 and DMT1 in NSCLC Cell Line H1299. Biological and Pharmacological Consequences.. Cells 8(4) PMID: 30959888
- 8. Zhang T et al.. 2026. Glutaredoxin 1 promotes intestinal epithelial cell copper toxicity in inflammatory bowel disease.. Redox Biol 93:104164 PMID: 41985411
