The MMR (macrophage mannose receptor), also known as MR, CD206, Mrc1, or CLEC13D, is a 175‑190 kDa endocytic receptor. It's expressed on M2 macrophages, tumor-associated macrophages (TAMs), and certain dendritic cells and endothelial cells. The human CD206 precursor (1456 aa) includes a signal sequence, an extracellular domain (ECD) with a cysteine-rich domain, a fibronectin type II repeat, eight C-type lectin domains (CTLDs), and N-glycosylation sites, followed by a transmembrane segment and a short cytoplasmic domain. The ECD can be shed by metalloproteinases. Human CD206 ECD shares high sequence identity with CD206 from other species.
The cysteine-rich domain binds pituitary hormones like LH and TSH, chondroitin sulfates, and sulfated N‑acetylgalactosamines. The FNII domain binds collagens without Ca2+, while CTLDs recognize branched sugars on pathogens in a Ca2+-dependent manner. CD206 internalizes ligands in clathrin-coated vesicles, sorts them to phagosomes or early endosomes, and recycles to the cell surface. It helps clear glycoproteins linked to allergy and inflammation, such as lysosomal hydrolases and myeloperoxidases. CD206 is involved in T cell polarization and cytokine production, facilitates peptide presentation on MHC II and cross-presentation on MHC I, which is crucial for tumor immunogenicity. This function may be blocked by tumor mucins engaging CD206 on TAMs.
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