1.A.56.1.2
Copper (Cu⁺) and silver (Ag⁺) uptake transporter, Ctr1. The trimeric channel Eisses and Kaplan, 2005) forms an oligomeric pore with each subunit displaying 3 TMSs and 2 metal binding motifs (Lee et al., 2007). TMS2 is sufficient to form the trimer and the MXXM motif bind Ag⁺ (Dong et al. 2015). Ctr1 mediates basolateral uptakes of Cu⁺ in enterocytes (Zimnicka et al., 2007) and shows copper-dependent internalization and recycling which provides a reversible mechanism for the regulation of cellular copper entry (Molloy and Kaplan, 2009). It acts as a receptor for the two extinct viruses, CERV1 and CERV2 (Soll et al., 2010). Ctrl takes up platinum anticancer drugs, cisplatin and carboplatin (Du et al., 2012). The 3-d structure is known (Yang et al., 2012).  Ctr1 has a low turn over number of about 10 ions/second/trimer (Maryon et al. 2013).  Methionine and histidine residues in the transmembrane domain are essential for transport of copper, but when mutated, they stimulated uptake of cisplatin (Larson et al. 2010).  Plays important roles in the developing embryo as well as in adult ionic homeostasis (Wee et al. 2013). (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells. EGCG inhibits the rapid degradation of CTR1 induced by cisplatin (cDDP). The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer (Wang et al. 2015). Steroid inhibitors may be able to overcome cycplatin resistance (Kadioglu et al. 2015).  Upregulated in colorectal cancer cells (Barresi et al. 2016). The N-terminus of CTR1 binds Cu²⁺ following transfer from blood copper carriers such as human serum albumin to the transporter (Bossak et al. 2018).