Fig. 3.

Eukaryotic metalloreductases and low valent copper and iron permeases. (a) The dominant plasma membrane metallo-reductase in fungi is a FRE protein, Fre1 in S. cerevisiae. Fungi express a canonical cuprous copper transporter, Ctr1, and a low-affinity ferrous iron uptake protein, Fet4. (b) Mammals express at least two distinct metalloreductases, Dcytb and a least two members of the Steap protein family, Steap3 and 4. The fungal and mammalian proteins share little homology but all contain inter-membrane porphyrins that function in shuttling electrons from cytosol to the exoplasm. For uptake, mammals express a canonical Ctr protein as well as two distinct families of ferrous iron transporters represented by DMT1 and Zip8/14.