SLC11A1
Description
The SLC11A1 (solute carrier family 11 member 1) is a protein-coding gene located on chromosome 2.
SLC11A1 is a gene that encodes a protein known as Natural resistance-associated macrophage protein 1 (NRAMP1). This protein is a member of the solute carrier family 11 (SLC11), which transports divalent metal ions across cell membranes using proton gradients. NRAMP1 is involved in iron metabolism and plays a crucial role in the host's resistance to certain pathogens. Mutations in SLC11A1 have been linked to increased susceptibility to infections like tuberculosis and leprosy, as well as inflammatory diseases like rheumatoid arthritis and Crohn's disease. Several different protein isoforms are produced from SLC11A1 through alternative splicing, but only one has been fully characterized.
SLC11A1 (also known as NRAMP1) acts as a macrophage-specific antiporter, facilitating the movement of metal ions across membranes against a proton gradient. It resides in late endosomal lysosomal membranes, transporting divalent cations from the cell's cytoplasm into these acidic compartments. This transport process directly influences antimicrobial activity, likely by impacting the availability of essential metals for pathogens. SLC11A1 is crucial for iron metabolism and plays a key role in the host's natural resistance to infections caused by intracellular parasites. It achieves pathogen resistance by sequestering iron (Fe2+) and manganese (Mn2+), which are essential cofactors for both prokaryotic and eukaryotic catalases and superoxide dismutases. This sequestration strategy serves two purposes: it protects the macrophage from its own reactive oxygen species production, and it deprives pathogens of these metals, hindering their ability to synthesize protective enzymes.
SLC11A1 is also known as LSH, NRAMP, NRAMP1.
