CLEC4M siRNA – C-Type Lectin Domain Family 4 Member M Isoform 12 (Human)

This gene encodes a transmembrane receptor and is often referred to as L-SIGN because of its expression in the endothelial cells of the lymph nodes and liver. The encoded protein is involved in the innate immune system and recognizes numerous evolutionarily divergent pathogens ranging from parasites to viruses, with a large impact on public health. The protein is organized into three distinct domains: an N-terminal transmembrane domain, a tandem-repeat neck domain and C-type lectin carbohydrate recognition domain. The extracellular region consisting of the C-type lectin and neck domains has a dual function as a pathogen recognition receptor and a cell adhesion receptor by binding carbohydrate ligands on the surface of microbes and endogenous cells. The neck region is important for homo-oligomerization which allows the receptor to bind multivalent ligands with high avidity. Variations in the number of 23 amino acid repeats in the neck domain of this protein are common and have a significant impact on ligand binding ability. This gene is closely related in terms of both sequence and function to a neighboring gene (GeneID 30835; often referred to as DC-SIGN or CD209). DC-SIGN and L-SIGN differ in their ligand-binding properties and distribution. Alternative splicing results in multiple variants.[provided by RefSeq, Feb 2009]

CLEC4M: Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Probably recognizes in a calcium-dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens, including HIV-1 gp120, HIV-2 gp120, SIV gp120, ebolavirus glycoproteins, HCV E2, and human SARS coronavirus protein S. Is a receptor for ICAM3, probably by binding to mannose-like carbohydrates. Is presumably a coreceptor for the SARS coronavirus. 10 isoforms of the human protein are produced by alternative splicing.

Protein type: Motility/polarity/chemotaxis; Membrane protein, integral

Chromosomal Location of Human Ortholog: 19p13

Cellular Component: membrane; integral to plasma membrane; cytoplasm; extracellular region

Molecular Function: mannose binding; peptide antigen binding; metal ion binding; virion binding; ICAM-3 receptor activity; receptor activity; carbohydrate binding; calcium-dependent protein binding

Biological Process: cell-cell recognition; antigen processing and presentation; leukocyte adhesion; regulation of gene expression; virus-host interaction; regulation of blood coagulation; innate immune response; endocytosis; peptide antigen transport; viral genome replication; virion attachment to host cell surface receptor