CD222 (CIMPR, cation-independent mannose 6-phosphate receptor; IGF2 receptor) is a ubiquitously expressed 250 kDa transmembrane protein. No more than 10% of CD222 is present on the cell surface where it serves as a multifunctional receptor. Intracellular (major) fraction of CD222 is involved in transport of newly synthesized lysosomal enzymes modified by mannose 6-phosphate from Golgi apparatus to lysosomes. The cell surface CD222 binds and internalizes exogeneous mannose 6-phosphate-containing ligands. Importantly, CD222 is crutial for internalization and degradation of insulin-like growth factor 2, thus controling cell growth. CD222 also complexes CD87 (urokinase-type plasminogen-activator receptor), plasminogen and latent TGF-beta, last but not least CD222 serves as a receptor for heparanase and even for Listeria.
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