High-affinity copper uptake protein 1 (CTR1) (CTR1)

High-affinity copper uptake protein 1 (CTR1), encoded by the SLC31A1 gene, is the primary transporter responsible for the influx of copper into mammalian cells (UniProt P44673). It exists as a homotrimer on the plasma membrane, where its extracellular N-terminal domain contains methionine-rich motifs (Mets motifs) that serve as essential copper-binding sites to facilitate ion translocation (PubMed 22506070). Beyond its physiological role in maintaining copper homeostasis, CTR1 is clinically significant as the major gateway for the cellular entry of platinum-based chemotherapeutic agents, such as cisplatin and carboplatin (PubMed 11830656). Reduced expression of CTR1 is frequently associated with the development of platinum resistance in various cancers, making it a critical factor in oncology treatment efficacy (PubMed 20154306). Furthermore, dysregulation of CTR1-mediated copper transport is linked to metabolic disorders like Menkes and Wilson diseases, as well as certain neurodegenerative conditions (PubMed 24123360). Targeting or modulating CTR1 activity offers potential strategies for enhancing chemotherapy sensitivity or managing copper-related pathologies.

Other names

Solute carrier family 31 member 1SLC31A1Copper transporter 1COPT1Copper ion binding site of CTR1

Facilitates the high-affinity uptake of cuprous copper (Cu+) and platinum-based chemotherapeutic agents across the plasma membrane into the cytoplasm via a pore formed by the CTR1 homotrimer (PubMed 11830656, PubMed 22506070).