TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
1.A.56.1.1









Plasma membrane copper uptake transporter; takes up Cu2+ into the cytoplasm (Andrés-Colás et al. 2010).  Met-rich motifs in the N-terminal region, an MXXXM motif in TMS-2, and a GXXXG motif in TMS-3 could be essential for Cu transport since they are highly conserved in all analyzed species (Vatansever et al. 2016). High-affinity copper transporters in Solanum lycopersicum have been characterized (Romero et al. 2021).

Eukaryota
Viridiplantae, Streptophyta
CopT1 of Arabidopsis thaliana
1.A.56.1.2









High affinity copper (Cu+) and silver (Ag+) uptake transporter, Ctr1 of 190 aas and 3 TMSs.  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). Ctr1 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).  ctr1 is 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). Once in the cytosol, enzyme-specific chaperones receive copper from the CTR1 C-terminal domain and deliver it to their apoenzymes (Ilyechova et al. 2019). Ctr1 is part of the Sp1-Slc31a1/Ctr1 copper-sensing system, and carnosine, a brain dipeptide, influences copper homeostasis in murine CNS-derived cells (Barca et al. 2019). A proteomic view of cellular responses of macrophages to copper has appeared (Dalzon et al. 2021). Tetrahedral framework nucleic acid delivered RNA therapeutics significantly attenuate pancreatic cancer progression via inhibition of CTR1-dependent copper absorption (Song et al. 2021). Electron paramagnetic resonance (EPR) has been used to study conformational changes during transport (Hofmann and Ruthstein 2022). Ctr1 is the main entry point for Cu' ions in eukaryotes. It  contains intrinsically disordered regions, IDRs, both at its N-terminal (Nterm) and C-terminal ends. The former delivers copper ions from the extracellular matrix to the selectivity filter in the Ctr1 lumen. Aupič et al. 2022 showed that Cu+ ions and a lipidic environment drive the insertion of the N-terminus into the Ctr1 selectivity filter, causing its opening. Through a lipid-aided conformational switch of one of the transmembrane helices, the conformational change of the selectivity filter propagates down to the cytosolic gate of Ctr1. Polymorphic renal transporters and cisplatin's toxicity in urinary bladder cancer patients have been reviewed (Selim et al. 2023).  Rosmarinic acid has a protective effect on Ctr1 expression in cisplatin-treated mice (Akhter et al. 2023).

Eukaryota
Metazoa, Chordata
SLC31A1 or Ctr1 of Homo sapiens
1.A.56.1.3









Vacuolar copper transporter (exports Cu+ from the vacuole to the cytoplasm; acts with Fre6 (Q12473: TC# 5.B.1.7.1) (metalo-reductase that reduces Cu2+ to Cu+ in the vacuole) (Rees and Thiele, 2007).
Eukaryota
Fungi, Ascomycota
Ctr2p of Saccharomyces cerevisiae
1.A.56.1.4









Copper uptake transporter
Eukaryota
Fungi, Ascomycota
Ctr3p of Saccharomyces cerevisiae
1.A.56.1.5









The heterodimeric high affinity copper uptake transporter, Ctr4/Ctr5. The Ctr4 central domain may mediate Cu2+ transport in this hetero-complex, whereas the Ctr5 carboxyl-terminal domain functions in the regulation of trafficking of the Cu2+ transport complex to the cell surface (Beaudoin et al., 2011).

Eukaryota
Fungi, Ascomycota
Ctr4/Ctr5 of Schizosaccharomyces pombe
Ctr4
Ctr5
1.A.56.1.6









Vacuolar, trimeric copper release protein (Beaudoin et al. 2013).

Eukaryota
Fungi, Ascomycota
Ctr6 of Schizosaccharomyces pombe
1.A.56.1.7









The CtrlB Copper transporter (expressed during late embryonic and larval stages of development in response to copper deprivation (Zhou et al., 2003).
Eukaryota
Metazoa, Arthropoda
CtrlB of Drosophila melanogaster
(Q9VHS6)
1.A.56.1.8









The plasma membrane copper import transporter, Ctr1A (3 isoforms in Drosophila, Ctr1A, 1B and 1C; Ctr1A but not Ctr1B is required for development) (Turski and Thiele, 2007)
Eukaryota
Metazoa, Arthropoda
Ctr1A of Drosophila melanogaster (Q9W3X9)
1.A.56.1.9









Probable low affinity copper uptake protein 2 (Ctr2) (present in the plasma membrane and interbal membranes where it stimulates copper uptake into the cytoplasm) (Bertinato et al., 2007; Wee et al. 2013).

Eukaryota
Metazoa, Chordata
SLC31A2 of Homo sapiens
1.A.56.1.10









The vacuolar copper transporter, Ctr2 (Involved in spore germination and pathogenesis (Barhoom et al., 2008))
Eukaryota
Fungi
Ctr2 of Colletotrichum gloeosporioides (A9XIK8)
1.A.56.1.11









Vacuolar/tonoplast copper transporter 5 (AtCOPT5).  It exports copper from the vacuole to the cytoplasm and is required for photosynthetic electron transport under comditions of copper deficiency.  It also promotes interorgan allocation of copper (Garcia-Molina et al. 2011; Klaumann et al. 2011Klaumann et al. 2011).

Eukaryota
Viridiplantae, Streptophyta
COPT5 of Arabidopsis thaliana
1.A.56.1.12









Putative copper transporter 5.2 (OsCOPT5.2)
Eukaryota
Viridiplantae, Streptophyta
COPT5.2 of Oryza sativa subsp. japonica
1.A.56.1.13









Copper transporter 3 (OsCOPT3)
Eukaryota
Viridiplantae, Streptophyta
COPT3 of Oryza sativa subsp. japonica
1.A.56.1.14









Copper uptake system, COPT6. Interacts with itself and its homologue, COPT1. Regulated by copper availability by using SPL7 (Jung et al., 2012). 

Eukaryota
Viridiplantae, Streptophyta
COPT6 of Arabidopsis thaliana (Q8GWP3)
1.A.56.1.15









Copper transport channel, PF14_0369 or CTR1 of 235 aas and 4 TMSs in a 1 (N-terminal) + 1 (central) + 2 (C-terminal) TMS arrangement (Choveaux et al. 2012). It binds Cu+ and is present in both the erythrocyte and parasite plasma membranes (Choveaux et al. 2012).

Eukaryota
Apicomplexa
Copper transporter of Plasmodium falciparum
1.A.56.1.16









Plasma membrane copper uptake channel of 257 aas, CtrC (Park et al. 2014).

Eukaryota
Fungi, Ascomycota
CtrC of Neosartorya fumigata (Aspergillus fumigatus)
1.A.56.1.17









Grape vacuolar copper transporter, Ctr1 (Martins et al. 2012).

Eukaryota
Viridiplantae, Streptophyta
Ctr1 of Vitis vinifera
1.A.56.1.18









Putative copper uptake transporter of 242 aas, CtrB (Park et al. 2014).

Eukaryota
Fungi, Ascomycota
CtrB of Neosartorya fumigata (Aspergillus fumigatus)
1.A.56.1.19









High affinity copper uptake transporter, Ctr-1, Ctr1 or Slc31a1 of 188 aas and 3 or 4 TMSs in a 1 or 2 + 2 TMS arrangement. It is maternally loaded, and transcripts can be detected throughout development and in adult fish. Distribution of ctr1 message appears ubiquitous during early stages, becoming restricted to the brain and ventral tissues by 24 h post fertilization. Beginning at 3 days post fertilization, expression is found mainly in the developing intestine. Knockdown of ctr1 by antisense morpholino oligonucleotides causes early larval lethality (Mackenzie et al. 2004).

Eukaryota
Metazoa, Chordata
Ctr1 of Danio rerio (Zebrafish) (Brachydanio rerio)
1.A.56.1.20









CTR2 of 160 aas and 4 TMSs in a 1 (N=terminal) + 1 (middle) + 2 TMS (C-terminal) arrangement (Wunderlich 2022).

Eukaryota
Apicomplexa
CTR2 of Plasmodium falciparum
1.A.56.2.1









Plasma membrane high affinity copper transporter, Ctr1p (Puig et al., 2002); acts with Fre1 (P32791: TC# 5.B.1.5.1) (metalo-reductase that reduces Cu2+ to Cu+ at the cell surface (Rees and Thiele, 2007).
Eukaryota
Fungi, Ascomycota
Ctr1p of Saccharomyces cerevisiae
1.A.56.2.2









High affinity copper transporter, Ctr1p (Marvin et al., 2004)
Eukaryota
Fungi, Ascomycota
Ctr1p of Candida albicans (CAB878806)
1.A.56.3.1









Ctr1 assimilatory copper transporter (has a Cx2(Mx2)2 (C-x)5 motif) (Page et al. 2009).
Eukaryota
Viridiplantae, Chlorophyta
Ctr1 of Chlamydomonas reinhardtii (Q4U0V9)
1.A.56.3.2









Copper uptake porter, CtrA2 (Park et al. 2014).

Eukaryota
Fungi, Ascomycota
CtrA2 of Neosartorya fumigata (Aspergillus fumigatus)
1.A.56.3.3









Uncharacterized protein of 244 aas and 3 TMSs

Eukaryota
UP of Vitrella brassicaformis