SEQUENCE ANALYSES AND PHYLOGENETIC CHARACTERIZATION OF THE ZIP FAMILYOF METAL-ION TRANSPORT PROTEINS

Several novel but similar heavy metal ion transporters, Zrt1, Zrt2, Zi p1-4 and Irt1, have recently been characterized. Zrt1, Zrt2 and Zip1-4 are probably zinc transporters in Saccharomyces cerevisiae and Arabid opsis thaliana whereas Irt1 appears to play a role in iron uptake in A . thaliana. The family of proteins including these functionally charac terized transporters has been designated the Zrt- and Irt-related prot ein (ZIP) family. In this report, ZIP family proteins in the current d atabases were identified and multiply aligned, and a phylogenetic tree for the family was constructed. A family specific signature sequence was derived, and the available sequences were analyzed for residues of potential functional significance. A fully conserved intramembranous histidyl residue, present within a putative amphipathic, alpha-helical , transmembrane spanning segment, was identified which may serve as a part of an intrachannel heavy metal ion binding site. The occurrence o f a proposed extramembranal metal binding motif (H X H X H) was examin ed in order to evaluate its potential functional significance for vari ous members of the family. The computational analyses reported in this topical review should serve as a guide to future researchers interest ed in the structure-function relationships of ZIP family proteins.