FIGURE 1: Predicted topology of the eukaryotic UPF0016 members. The eukaryotic UPF0016 members are predicted to consist of two clusters of three transmembrane spans assembled in an antiparallel orientation and separated by a central loop enriched in negatively charged residues found at the cytosolic side in yeast, human, and bacteria. The featured UPF0016 motif Glu-φ-Gly-Asp-(Arg/Lys)-(Ser/Thr) is found in two copies, in the transmembrane spans one and four. Due to the hydrophilic nature of the residues found in this motif, and its localization in hydrophobic transmembrane spans, their two copies were hypothesized to form the pore of the protein through which the transported ions would cross the membrane [1].

1. Demaegd D, Colinet AS, Deschamps A, Morsomme P (2014). Molecular evolution of a novel family of putative calcium transporters. PLoS ONE 9(6). 10.1371/journal.pone.0100851