The SLC39 (ZIP) family of zinc transporters have now been identified at all phylogenetic levels. SLC39 transporters are responsible for zinc transport into the cytoplasm across cellular membranes, i.e. either influx from the extracellular space or efflux from intracellular organelles.
Zinc is a trace element nutrient which is vital for life. This mineral acts as a cofactor for enzymes involved in critical biochemical processes and it also plays numerous structural roles. At the cellular level, zinc is tightly regulated and destruction of zinc homeostasis leads to serious physiological or pathological problems. Although zinc is highly demanded in cells, free or labile zinc must be kept at very low levels. Two major zinc transporter families in humans, the SLC30 (ZnT) family and SLC39 family control cellular zinc homeostasis. SLC39 transporters are primarily used to transfer zinc into the cytoplasm and play key roles in maintaining cellular zinc homeostasis.
ZIP transporters play different roles in the physiology of cells and organisms. Their genes are expressed in a variety of tissues and cell types, and their proteins are localized to distinct subcellular compartments. Some ZIPs are regulated by dietary zinc, while others are responsive to hormonal signaling. This differential expression, subcellular localization, and transcriptional or post-transcriptional regulation offer clues to understanding the unique physiological roles of each ZIP transporter.
Fig.1 Subcellular localization of human ZIP transporters. (Jeong, 2013)
SLC39 proteins have been grouped into four subfamilies. There are 14 members of the SLC39 transporters encoded in the human genome, which are designated SLC39A1-SLC39A14 and encode the proteins ZIP1-ZIP14, respectively.
Human SLC39 (ZIP) Family Members | |||||
SLC39A1 | SLC39A2 | SLC39A3 | SLC39A4 | SLC39A5 | SLC39A6 |
SLC39A8 | SLC39A9 | SLC39A10 | SLC39A13 | SLC39A14 |
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