SLC39A8
Description
The SLC39A8 (solute carrier family 39 member 8) is a protein-coding gene located on chromosome 4.
SLC39A8, also known as ZIP8, is a transmembrane protein responsible for transporting zinc, manganese, iron, and cadmium into cells. It is essential for development, particularly in the heart, where it is localized in endothelial cells. SLC39A8 is involved in the regulation of cardiac development, which is a zinc-dependent process. During embryonic development, SLC39A8 is expressed in the embryo, placenta, and yolk sac. Its highest concentration is observed during the developmental period of different organ systems, particularly the heart. SLC39A8 is crucial for the formation of trabeculae, which are protrusions of cardiomyocytes into the cardiac jelly, facilitating nutrient and oxygen exchange. It also plays a role in the compaction of the ventricular wall, a process that follows trabeculation. SLC39A8 indirectly regulates Notch 1 signaling, a key pathway involved in cardiomyocyte differentiation, proliferation, and trabeculae patterning. SLC39A8 interacts with ADAMTS metalloenzymes, which degrade the extracellular matrix (ECM), enabling compaction.
SLC39A8, also known as ZIP8, is a protein that transports divalent metal cations, such as zinc and manganese, across cell membranes. It plays a crucial role in the uptake of these essential minerals, which are vital for development, tissue homeostasis, and immunity. SLC39A8 also facilitates the uptake of selenium, an essential trace metal, and cadmium, a non-essential, cytotoxic, and carcinogenic metal. The protein can also transport iron and cobalt. In addition to its role in metal transport, SLC39A8 indirectly regulates the expression of genes involved in various cellular processes, including cell morphology, cytoskeleton organization, and innate immune function. It also protects cells from injury and death during inflammation. SLC39A8 regulates the activity of manganese-dependent enzymes by reclaiming manganese from bile at the apical membrane of hepatocytes. It also participates in manganese reabsorption in the kidneys and may contribute to manganese transport to the brain. SLC39A8 is also involved in mitochondrial function. It has been proposed that SLC39A8 functions intracellularly, translocating zinc from lysosomes to the cytosol, to enhance gene expression during T cell activation. {ECO:0000250|UniProtKB:Q91W10, ECO:0000269|PubMed:12504855, ECO:0000269|PubMed:18390834, ECO:0000269|PubMed:19401385, ECO:0000269|PubMed:22898811, ECO:0000269|PubMed:23403290, ECO:0000269|PubMed:26637978, ECO:0000269|PubMed:27166256, ECO:0000269|PubMed:27466201, ECO:0000269|PubMed:28056086, ECO:0000269|PubMed:28481222, ECO:0000269|PubMed:29337306, ECO:0000269|PubMed:29453449, ECO:0000269|PubMed:29927450, ECO:0000269|PubMed:31699897}
SLC39A8 is also known as BIGM103, CDG2N, LZT-Hs6, PP3105, ZIP8.
