SLC39A14 : solute carrier family 39 member 14
Description
The SLC39A14 (solute carrier family 39 member 14) is a protein-coding gene located on chromosome 8.
The SLC39A14 gene provides instructions for making a protein that transports the element manganese across cell membranes. Manganese is important for many cellular functions, but large amounts are toxic, particularly to brain cells. The SLC39A14 protein is found in the membranes surrounding several types of cells, as well as in the membranes of structures within these cells. The protein is thought to transport excess manganese from the blood into liver cells so that it can be removed from the body through bile. Bile is a substance produced by the liver that is important for digestion and the removal of waste products.The SLC39A14 protein may also transport other elements, including zinc, iron, and cadmium, across cell membranes. The importance of this transport in the body is not well understood.
SLC39A14 is an electroneutral transporter located on the plasma membrane, facilitating the uptake of divalent metal cations such as zinc, manganese, and iron. These metals are essential for various cellular processes including tissue homeostasis, metabolism, development, and immunity. The protein acts as an energy-dependent symporter, transporting a divalent metal cation along with two bicarbonate anions across the membrane. Besides these essential metals, SLC39A14 can also import cadmium, a toxic and carcinogenic metal. This transporter plays a key role in regulating zinc absorption in the intestinal epithelium, maintaining tight junctions and intestinal permeability. SLC39A14 can modify the activity of zinc-dependent phosphodiesterases, indirectly regulating G protein-coupled receptor signaling pathways involved in gluconeogenesis and chondrocyte differentiation. Additionally, SLC39A14 regulates insulin receptor signaling, glucose uptake, glycogen synthesis, and gluconeogenesis in hepatocytes by controlling the zinc-dependent intracellular catabolism of insulin. Its role in zinc uptake also contributes to the cellular adaptation to endoplasmic reticulum stress. SLC39A14 is a major manganese transporter on the basolateral membrane of intestinal epithelial cells, crucial for maintaining systemic manganese homeostasis through intestinal uptake. It also participates in manganese uptake by cells of the blood-brain barrier. The protein potentially plays a role in manganese and zinc homeostasis, aiding in their elimination from the blood through hepatobiliary excretion. SLC39A14 is involved in the extracellular uptake of free iron and might function intracellularly, mediating the transport of iron endocytosed by transferrin from endosomes to the cytosol. This protein contributes to innate immunity by regulating cytokine expression in activated macrophages.
SLC39A14 is also known as HCIN, HMNDYT2, LZT-Hs4, NET34, ZIP14, cig19.
Associated Diseases
- Hypermanganesemia with dystonia 2
- Hyperostosis cranialis interna
- Dystonia-parkinsonism-hypermanganesemia syndrome
- Hypermanganesemia with dystonia
