SLC31A1: Copper Transporter 1 (CTR1) - Key Regulator of Copper Homeostasis
Solute Carrier Family 31 Member 1: A high-affinity copper uptake protein critical for cellular copper balance, development, and cancer biology.
Gene Information Card
| Symbol | SLC31A1 |
|---|---|
| Full Name | Solute Carrier Family 31 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q32 |
| NCBI Gene ID | 1317 ncbi.nlm.nih.gov/gene/1317 |
| Ensembl ID | ENSG00000136868 |
| UniProt ID | P15473 |
| OMIM ID | 603085 |
| HGNC ID | 11016 |
| Aliases | CTR1, COPT1, hCTR1 |
Description
SLC31A1 (Solute Carrier Family 31 Member 1), commonly known as CTR1, encodes a high-affinity copper transporter that mediates the cellular uptake of copper ions. This protein is essential for maintaining intracellular copper homeostasis, which is critical for the function of copper-dependent enzymes involved in oxidative phosphorylation, antioxidant defense, neurotransmitter synthesis, and iron metabolism. SLC31A1 is also the primary route for the uptake of platinum-based chemotherapeutic agents such as cisplatin, linking its expression to cancer drug sensitivity and resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Copper deficiency (Menkes disease-like phenotype) | Loss-of-function mutations in SLC31A1 impair copper import, leading to systemic copper deficiency and neurological symptoms. | OMIM #603085; PMID: 11590112 |
| Copper overload (Wilson disease modifier) | Altered SLC31A1 expression may modulate copper accumulation in the liver, influencing Wilson disease severity. | PMID: 17506658 |
| Platinum-resistant cancers (ovarian, lung, colorectal) | Downregulation of SLC31A1 reduces cisplatin uptake, conferring chemoresistance. | COSMIC; PMID: 17909007 |
| Neurodegenerative disorders (Alzheimer's disease) | Dysregulated copper transport via SLC31A1 may contribute to amyloid-beta aggregation and oxidative stress. | PMID: 23382115 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Kidney | 10.8 | Medium |
| Small intestine | 9.5 | Medium |
| Brain | 6.2 | Low |
| Heart | 5.1 | Low |
| Lung | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 12.7 | High expression |
| A549 (lung) | 8.3 | Medium expression |
| MCF7 (breast) | 6.1 | Low expression |
| SKOV3 (ovarian) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.211C>T (p.Arg71Trp) | Missense | <0.01% | Reduced copper uptake; associated with copper deficiency |
| c.347G>A (p.Gly116Asp) | Missense | <0.01% | Impaired protein trafficking to plasma membrane |
| c.502_504del (p.Lys168del) | In-frame deletion | <0.01% | Loss of copper transport activity |
| c.1A>G (p.Met1Val) | Start loss | <0.01% | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt copper import (e.g., p.Arg71Trp, p.Lys168del) lead to cellular copper deficiency and impaired cuproenzyme activity.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in SLC31A1.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for SLC31A1.
View complete mutation data：
Gene Ontology (GO)
| • copper ion transmembrane transporter activity (GO:0005375) | • copper ion import (GO:0015677) |
| • integral component of membrane (GO:0016021) | • copper ion transmembrane transport (GO:0035434) |
| • plasma membrane (GO:0005886) | • response to copper ion (GO:0046688) |
Pathways
• Copper homeostasis (Reactome: R-HSA-437239)
• Cisplatin resistance (KEGG: hsa01524)
• Metal ion SLC transporters (KEGG: hsa04976)
Protein Summary
The SLC31A1 protein (CTR1) is a 190-amino-acid, three-transmembrane-domain protein that forms homotrimeric channels at the plasma membrane. It selectively transports Cu(I) ions with high affinity using a methionine-rich motif. CTR1 is essential for embryonic development, as knockout mice are embryonic lethal. The protein also mediates the uptake of cisplatin, oxaliplatin, and carboplatin, linking its expression levels to chemotherapeutic efficacy. Post-translational regulation includes copper-dependent endocytosis and degradation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC31A1 Knockout HEK293 Cell Line | EDJ-KQ3173 | Human | 1317 | Details Get a Quote |
| SLC31A1 Knockout A-549 Cell Line | EDJ-KQ24594 | Human | 1317 | Details Get a Quote |
| SLC31A1 Knockout HCT 116 Cell Line | EDJ-KQ24595 | Human | 1317 | Details Get a Quote |
| SLC31A1 Knockout HeLa Cell Line | EDJ-KQ24596 | Human | 1317 | Details Get a Quote |
