Aerobic organisms possess efficient systems for the transport of copper. This 
involves transporters that mediate the passage of copper across biological 
membranes to reach essential intracellular copper-requiring enzymes. In this 
report, we identify a new copper transporter in Schizosaccharomyces pombe, 
encoded by the ctr6(+) gene. The transcription of ctr6(+) is induced under 
copper-limiting conditions. This regulation is mediated by the cis-acting 
promoter element CuSE (copper-signaling element) through the copper-sensing 
transcription factor Cuf1. An S. pombe strain bearing a disrupted ctr6Delta 
allele displays a strong reduction of copper,zinc superoxide dismutase activity. 
When the ctr6+ gene is overexpressed from the thiamine-inducible nmt1(+) 
promoter, the cells are unable to grow on medium containing exogenous copper. 
Surprisingly, this copper-sensitive growth phenotype is not due to an increase 
of copper uptake at the cell surface. Instead, copper delivery across the plasma 
membrane is reduced. Consistently, this results in repressing ctr4(+) gene 
expression. By using a functional ctr6(+) epitope-tagged allele expressed under 
the control of its own promoter, we localize the Ctr6 protein on the membrane of 
vacuoles. Furthermore, we demonstrate that Ctr6 is an integral membrane protein 
that can trimerize. Moreover, we show that Ctr6 harbors a putative 
copper-binding Met-X-His-Cys-X-Met-X-Met motif in the amino terminus, which is 
essential for its function. Our findings suggest that under conditions in which 
copper is scarce, Ctr6 is required as a means to mobilize stored copper from the 
vacuole to the cytosol.