C-type lectin domain family 4 member M (CLEC4M)

C-type lectin domain family 4 member M (CLEC4M), also known as L-SIGN (Liver/Lymph node-Specific ICAM-3-Grabbing Non-integrin), is a type II integral membrane receptor highly expressed in liver and lymph node endothelial cells. It possesses a C-terminal carbohydrate recognition domain (CRD), a flexible tandem-repeat neck domain, a transmembrane segment, and a cytoplasmic domain. CLEC4M functions in cell adhesion and peripheral immune surveillance, recognizing a wide range of pathogens, including multiple viruses (HIV-1, hepatitis C, Ebola, SARS-CoV, and others) and microbiota such as tuberculosis mycobacteria. It binds intercellular adhesion molecules like ICAM-3 and mediates endocytosis and internalization of pathogens for lysosomal degradation. CLEC4M also acts as a clearance receptor for von Willebrand factor (VWF), influencing plasma VWF levels through gene polymorphisms in its neck domain. The receptor is closely related to DC-SIGN (CD209) but differs in tissue distribution and pathogen recognition profiles. Polymorphisms in CLEC4M modulate susceptibility to infection and plasma VWF variability. Experimental evidence links CLEC4M to disease risk in infections and bleeding disorders but currently no approved drugs target this receptor directly.

Other names

L-SIGNCD209LCD299DC-SIGNRDC-SIGN2CD209 antigen-like protein 1DC-SIGN-related proteinLiver/lymph node-specific ICAM-3-grabbing non-integrinDendritic cell-specific ICAM-3-grabbing non-integrin 2Mannose binding C-type lectin DC-SIGNRCLEC4M

Competitive inhibition of viral binding (e.g., mannan blocks the carbohydrate recognition domain); modulation of immune response or pathogen clearance (research focus); and modulation of binding and internalization of von Willebrand factor (VWF) in context of bleeding disorders.