Zinc transporter ZIP8 (short for ZIP-8), alternatively known as BCG-induced integral membrane protein in monocyte clone 103 protein, or LIV-1 subfamily of ZIP zinc transporter 6 (LZT-Hs6), is encoded by the SLC39A8 gene in human. The zinc transporter SLC39A8 is a member of the ZIP (Zrt- and Irt-like protein) family of metal ion transporters, which is also called the solute carrier family 39 (SLC39). SLC39A8 is highly expressed in the pancreas. And SLC39A8 is also found in placenta, thymus, lung, pancreas, liver, and to a smaller extent, in spleen, heart, ovary, testis, colon, small intestine, leukocyte.
|Basic Information of SLC39A8|
|Protein Name||Zinc transporter ZIP8|
|Aliases||BCG-induced integral membrane protein in monocyte clone 103 protein, Solute carrier family 39 member 8, Zrt- and Irt-like protein 8 (ZIP-8), LIV-1 subfamily of ZIP zinc transporter 6 (LZT-Hs6)|
|Organism||Homo sapiens (Human)|
Zinc transporter SLC39A8 is glycosylated and expressed in the mitochondria and plasma membrane, and it plays a role in the cellular import of zinc at the onset of inflammation. It also acts as a manganese and cadmium transporter. A study showed that SLC39A8 can also mediate the cellular uptake of iron, identifying it as the third mammalian transmembrane iron import protein. Aided by an intracellular zinc-selective fluorescent dye, it has been observed that CHO cells stably transfected with SLC39A8 accumulate and retain more zinc, as compared to other ZIP family members. SLC39A8 is also considered to be the main transporter of the toxic cation cadmium, which is found in cigarette smoke. The SLC39A8 protein shows high expression in T cells derived from human subjects and may provide a secondary level of IFN-gamma regulation in T cells, by control of zinc transport from the lysosome. Moreover, SLC39A8 is proved to contribute to the manganese reabsorption in the proximal tubule of the kidney and to the manganese uptake into the brain.
Fig.1 Subcellular localization of Zn transporters and MTs. (Miao, 2013)
This study suggests that Zip8 is a vital regulator of neuroblastoma cell proliferation and migration, indicating that Zip8 can be a potential therapeutic target for cancer and a promising diagnostic biomarker for human neuroblastoma.
Authors of this article emphasize that the expression, localization, and function of ZIP8, which has important implications for TB prevention and dissemination.
This study reported a novel SLC39A8 variant in siblings with features of the Leigh-like mitochondrial disease. Meanwhile, the results suggest SLC39A8 deficiency can cause both type II CDG and Leigh-like syndrome.
The results of this study indicate that hepatic ZIP8 reclaims Mn from bile and regulates whole-body Mn homeostasis, and thus modulating the activity of Mn-dependent enzymes.
Results of this study demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10.
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