This entry represents the C-type lectin-like domain (CTLD) of the type found in human dendritic cell (DC)-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), also known as CD209 antigen, and the related receptor, DC-SIGN receptor (DC-SIGNR), also known as CD209 antigen-like protein 1 or C-type lectin domain family 4 member M. This group also contains proteins similar to hepatic asialoglycoprotein receptor (ASGP-R) and langerin (also known as CD207 or C-type lectin domain family 4 member K) in human. These proteins are type II membrane proteins with a CTLD ectodomain. CTLD refers to a domain homologous to the carbohydrate-recognition domains (CRDs) of the C-type lectins [].DC-SIGN is thought to mediate the initial contact between dendritic cells and resting T cells, and may also mediate the rolling of DCs on epithelium []. DC-SIGN and DC-SIGNR bind to oligosaccharides present on human tissues, as well as on pathogens including parasites, bacteria, and viruses. DC-SIGN and DC-SIGNR bind to HIV, enhancing viral infection of T cells []. DC-SIGN and DC-SIGNR are homotetrameric, and contain four CTLDs stabilized by a coiled coil of alpha helices []. The hepatic ASGP-R is an endocytic recycling receptor which binds and internalizes desialylated glycoproteins having a terminal galactose or N-acetylgalactosamine residues on their N-linked carbohydrate chains, via the clathrin-coated pit mediated endocytic pathway, and delivers them to lysosomes for degradation. It has been proposed that glycoproteins bearing terminals 'Sia (sialic acid) alpha2, 6GalNAc' and 'Sia alpha2, 6Gal' are endogenous ligands for ASGP-R, and that ASGP-R participates in regulating the relative concentration of serum glycoproteins bearing alpha 2,6-linked Sia []. The human ASGP-R is a hetero-oligomer composed of two subunits, both of which are found within this group []. Langerin is expressed in a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin induces the formation of Birbeck Granules (BGs) and associates with these BGs following internalization []. Langerin binds, in a calcium-dependent manner, to glyco-conjugates containing mannose and related sugars mediating their uptake and degradation. Langerin molecules oligomerize as trimers with three CTLDs held together by a coiled-coil of alpha helices [].
