Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.

The Zrt/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent -block metal transporters that play central roles in the uptake, secretion, excretion, and distribution of several essential and toxic metals in living organisms. The past few years has witnessed rapid progress in the molecular basis of these membrane transport proteins. In this critical review, we summarize the research progress at the molecular level of the ZIP family and discuss the future prospects. Furthermore, an evolutionary path for the unique ZIP fold and a new classification of the ZIP family are proposed based on the presented structural and sequence analyses.