CLEC4M

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]

Full Name

C-Type Lectin Domain Family 4 Member M

Function

Probable pathogen-recognition receptor involved in peripheral immune surveillance in liver. May mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments. Is a receptor for ICAM3, probably by binding to mannose-like carbohydrates.

(Microbial infection) Acts as an attachment receptor for Ebolavirus.

(Microbial infection) Acts as an attachment receptor for Hepatitis C virus.

(Microbial infection) Acts as an attachment receptor for HIV-1.

(Microbial infection) Acts as an attachment receptor for Human coronavirus 229E.

(Microbial infection) Acts as an attachment receptor for Human cytomegalovirus/HHV-5.

(Microbial infection) Acts as an attachment receptor for Influenzavirus.

(Microbial infection) Acts as an attachment receptor for SARS-CoV.

(Microbial infection) Acts as an attachment receptor for West-nile virus.

(Microbial infection) Acts as an attachment receptor for Japanese encephalitis virus.

(Microbial infection) Acts as an attachment receptor for Marburg virus glycoprotein.

(Microbial infection) Recognition of M.bovis by dendritic cells may occur partially via this molecule.

Biological Process

Adaptive immune response Source: UniProtKB-KW
Antigen processing and presentation Source: UniProtKB
Cell-cell recognition Source: UniProtKB
Endocytosis Source: UniProtKB-KW
Innate immune response Source: UniProtKB-KW
Intracellular signal transduction Source: UniProtKB
Intracellular transport of virus Source: UniProtKB
Leukocyte cell-cell adhesion Source: UniProtKB
Modulation by virus of host process Source: UniProtKB
Peptide antigen transport Source: UniProtKB
Viral entry into host cell Source: FlyBase
Viral genome replication Source: UniProtKB
Virion attachment to host cell Source: UniProtKB

Cellular Location

Isoform 1&2&3: Cell membrane
Isoform 5&6&7&10: Secreted

Topology

Cytoplasmic: 1-49
Helical: 50-70
Extracellular: 71-399