CLEC4A
Domain
Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases (PubMed:20530286). Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases (PubMed:20530286). ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases is required for HIV-1 binding/entry and virus infection (PubMed:20530286).
Function
C-type lectin receptor that binds carbohydrates mannose and fucose but also weakly interacts with N-acetylglucosamine (GlcNAc) in a Ca(2+)-dependent manner (PubMed:27015765). Involved in regulating immune reactivity (PubMed:10438934, PubMed:18258799). Once triggered by antigen, it is internalized by clathrin-dependent endocytosis and delivers its antigenic cargo into the antigen presentation pathway resulting in cross-priming of CD8(+) T cells. This cross-presentation and cross-priming are enhanced by TLR7 and TLR8 agonists with increased expansion of the CD8(+) T cells, high production of IFNG and TNF with reduced levels of IL4, IL5 and IL13 (PubMed:18258799, PubMed:20530286). In plasmacytoid dendritic cells, inhibits TLR9-mediated IFNA and TNF production (PubMed:18258799). May be involved via its ITIM motif (immunoreceptor tyrosine-based inhibitory motifs) in the inhibition of B-cell-receptor-mediated calcium mobilization and protein tyrosine phosphorylation (PubMed:10438934).
(Microbial infection) Involved in the interaction between HIV-1 virus and dendritic cells. Enhances HIV-1 binding/entry and virus infection. Requires ITIM motif-associated signal transduction pathway involving phosphatases PTPN6 and PTPN11, SYK, Src kinases and MAP kinases.
Tissue Specificity
Expressed preferentially in hematopoietic tissues. Expressed in all circulating Ag-presenting cells such as dendritic cells, myeloid cells, monocytes, macrophages, B-cells and epidermal Langerhans cells (at protein level). Expressed in peripheral blood leukocytes, neutrophils, moderate quantities in spleen, lymph node, and bone marrow, and at very low levels in thymus.
Cellular localization
- Cell membrane
- Single-pass type II membrane protein
- Extracellular side
Alternative names
CD367, CLECSF6, DCIR, LLIR, HDCGC13P, CLEC4A, C-type lectin domain family 4 member A, C-type lectin DDB27, C-type lectin superfamily member 6, Dendritic cell immunoreceptor, Lectin-like immunoreceptor