CLEC4F (C-type lectin domain; family 4, member F; also known as the Kupffer cell receptor and fucose receptor) is an 80kD, type II transmembrane glycoprotein member of the C-type lectin superfamily (1-3). Mature mouse CLEC4F consists of a 42 amino acid (aa) cytoplasmic domain, a 27 aa transmembrane segment, and a 479 aa extracellular domain (ECD) that contains an extended stalk region plus one carbohydrate recognition domain (4, 5). Within the ECD, mouse CLEC4F shares 48% and 79% aa sequence identity with human and rat CLEC4F, respectively. The stalk region of CLEC4F is a coiled coil domain that mediates homotrimer formation (6, 7). CLEC4F is expressed on Kupffer cells in the liver, but not on macrophages in other tissues (8). CLEC4F preferentially binds galactose and N-acetylgalactosamine in a calcium-dependent manner (6, 9, 10). Its activity at neutral, but not at acidic pH, suggests a capacity to internalize and release ligands into the endosomal system (11).
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