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Description

Zinc transporter ZIP8 (UniProt Q9C0K1, also known as BCG-induced integral membrane protein in monocyte clone 103 protein, LIV-1 subfamily of ZIP zinc transporter 6, LZT-Hs6, Solute carrier family 39 member 8, ZIP-8, Zrt- and Irt-like protein 8) is encoded by the SLC39A8 (also known as BIGM103, ZIP8, PP3105) gene (Gene ID 64116) in human. Zinc transporters mediate the transport of zinc ions into intracellular compartments as well as the export of excess zinc out of cells. Disruption of zinc homeostasis is responsible for many chronic neurodegenerative diseases and acute neural injuries. Excessive and inadequate levels of bioavailable zinc are detrimental to the health of neurons. Two classes of multipass transmembrane Zn transporters are known, including 10 ZnTs and 14 ZIPs, that exhibit opposing functions in mediating zinc homeostasis. These transporters are located on plasma and vesicular membranes with tissue-specific expression pattern. ZIP8 is a negative regulator of the NF-kappaB signaling pathway through zinc-mediated suppression of IKK activity in monocytes, macrophages, and lung epithelia. ZIP8 expression is induced following innate immune activation and correlates with intracellular zinc sequestration. Human ZIP8 is an 8-transmembrane protein (a.a. 9-29, 133-153, 161-181, 192-212, 303-323, 366-386, 389-409, 430-450) that has both its N- and C-termini (a.a. 1-8 & 451-460) exposed extracelluarly with 4 intracellular and 3 extracellular loops in between.

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