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Description

Zinc transporter 8 (UniProt: Q8IWU4, also known as ZnT-8, Solute carrier family 30 member 8) is encoded by the SLC30A8 (also known as ZNT8) gene (Gene ID: 169026) in human. Zinc is required for insulin crystallization, storage, and secretion in the secretory granules of pancreatic beta-cells. Delivery of Zn2+ into the insulin-containing granules is largely accomplished by the ZnT8 protein. ZnT8 is a homodimeric, multi-pass membrane protein with four cytoplasmic domains, six transmembrane domains, and three extracellular domains. It serves as a granule-specific Zn2+ transporter that is abundantly expressed in pancreatic islet cells. It contains a histidine-rich region, HXXXXXHNH-motif, in its third cytoplasmic domain, which serves as a ligand for zinc. ZnT8 is expressed in both a and b cells, but not in ? cells. It plays a major role in Zn2+ uptake into the secretory granules. During stimulated secretion, Zn2+ is shown to be co-released with other granular content into the extracellular medium.Loss of ZnT8 function is reported to reduce total islet Zn2+ content as well as free Zn2+ in the cytosol and granules. Loss of ZnT8 also results in reduced dense core granules and increased granule diameter. Studies have shown that the expression of ZnT8 is significantly reduced in the islets of diabetic murine models. Two isoforms of ZnT8 have been described that are produced by alternative splicing. (Ref.: Ghazvini Zadeh, EH., et al. (2020). Cell Reports 32(2), 107904, Dwivedi, OP., et al. (2019). Nat. Genetics. 51(11), 1596-1606).