Family 9.A.12 - The Copper Transporter-2 Family       

Family ID: 52660

Four proteins, one from Arabidopsis thaliana(CopT1; 169 amino acyl residues), one from humans (hCTR1; 190 residues) and two from Saccharomyces cerevisiae(Ctr2p; 189 residues and Ctr3p; 241 residues) have been cloned, sequenced and expressed in mutant S. cerevisiae. They have three homologues in Schizosaccharomyces pombe(148, 173 and 389 residues), six homologues in the worm, C. elegans(162, 178, 252, 253, 359 and 387 residues), three in Drosophilia melanogastor(174, 220 and 274 residues), one in humans (143 residues) and two in the protozoan Theileria parva(480 and 543 residues). These proteins exhibit 1, 2 or 3 repeat units of about 124 residues each. Thus, CopT1of A. thaliana has one, Ctr3p of S. cerevisiaehas 2, and the C. elegansprotein K12C11.3 (387 residues) has 3 repeats.

The H. sapiens, A. thaliana, S. cerevisiae and T. parva proteins have 3 putative transmembrane a-helical spanners and display N-terminal hydrophilic sequences homologous to the methionine and histidine-rich Cu+ binding domains of various copper binding proteins. These copper binding proteins include the P-type copper-transporting ATPases (TC #3.A.3). It is not clear that all of these proteins are localized to the plasma membrane, but the majority of the evidence implicates them in Cu+ uptake. The energy coupling mechanism (if any) has not been investigated. However, the mouse Ctr1 transporter is essential for copper homeostasis and embryonic development (Andrews, 2001; Kuo et al., 2001; Lee et al., 2001).

In S. pombe, two proteins, Ctr4 and Ctr5, together comprise a heteromeric Cu2+ uptake transporter. Both proteins exhibit regions of strong sequence similarity with Ctr3 of S. cerevisiae. They exhibit 2 and 3 putative TMSs, respectively, and are coregulated by Cu2+ and the Cuf1 transcription factor. They have been shown to physically interact to yield the active transporter.