CLEC7A

CLEC7A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2BPD, 2BPE, 2BPH, 2CL8
Identifiers
Aliases	CLEC7A, BGR, CANDF4, CLECSF12, DECTIN1, CD369, SCARE2, C-type lectin domain family 7 member A
External IDs	MGI: 1861431 HomoloGene: 49606 GeneCards: CLEC7A
Gene ontology Molecular function • MHC protein binding • signaling pattern recognition receptor activity • metal ion binding • protein binding • carbohydrate binding Cellular component • cytoplasm • integral component of membrane • intracellular membrane-bounded organelle • membrane • plasma membrane • nucleoplasm Biological process • cellular response to molecule of fungal origin • cell recognition • immune system process • carbohydrate mediated signaling • leukocyte activation involved in immune response • stimulatory C-type lectin receptor signaling pathway • phagocytosis, recognition • inflammatory response • T cell activation • defense response to protozoan • pattern recognition receptor signaling pathway • innate immune response Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	64581	56644
Ensembl	ENSG00000172243	ENSMUSG00000079293
UniProt	Q9BXN2	Q6QLQ4
RefSeq (mRNA)	NM_022570 NM_197947 NM_197948 NM_197949 NM_197950 NM_197951 NM_197952 NM_197953 NM_197954	NM_020008 NM_001309637
RefSeq (protein)	NP_072092.2 NP_922938.1 NP_922939.1 NP_922940.1 NP_922941.1 NP_922945.1	n/a
Location (UCSC)	Chr 12: 10.12 – 10.13 Mb	Chr 6: 129.46 – 129.47 Mb
PubMed search	[1]	[2]
Wikidata

C-type lectin domain family 7 member A or Dectin-1 is a protein that in humans is encoded by the CLEC7A gene.^[3] CLEC7A is a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded glycoprotein is a small type II membrane receptor with an extracellular C-type lectin-like domain fold and a cytoplasmic domain with a partial immunoreceptor tyrosine-based activation motif. It functions as a pattern-recognition receptor for a variety of β-1,3-linked and β-1,6-linked glucans from fungi and plants, and in this way plays a role in innate immune response. Expression is found on myeloid dendritic cells, monocytes, macrophages and B cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region.^[3]

Structure

Dectin-1 is a transmembrane protein containing an immunoreceptor tyrosine-based activation (ITAM)-like motif in its intracellular tail (which is involved in cellular activation) and one C-type lectin-like domain (carbohydrate-recognition domain, CRD) in the extracellular region (which recognizes β-glucans and endogenous ligands on T cells). The CRD is separated from the membrane by a stalk region. CLEC7A contains putative N-linked sites of glycosylation in the stalk region.^[4][5]

CLEC7A is expressed by macrophages, neutrophils and dendritic cells.^[6] Expression has also been studied on other immune cells including eosinophils and B cells.^[7]

Function

The C-type lectin receptors are class of signalling pattern recognition receptors which are involved in antifungal immunity, but also play important roles in immune responses to other pathogens such as bacteria, viruses and nematodes.^[4] As a member of this receptor family, dectin-1 recognizes β-glucans and carbohydrates found in fungal cell walls, some bacteria and plants, but may also recognize other unidentified molecules (endogenous ligand on T-cells and ligand on mycobacteria).^[4] Ligand binding induces intracellular signalling via the ITAM-like motif. CLEC7A can induce both Syk dependent or Syk independent pathways. Dimerization of dectin-1 upon ligand binding leads to tyrosine phosphorylation by Src family kinases and recruitment of Syk. Syk activates transcription factor NFκB. This transcription factor is responsible for the production of numerous inflammatory cytokines^[7] and chemokines such as TNF, IL-23, IL-6, IL-2. Other responses include: respiratory burst, production of arachidonic acid metabolites, dendritic cell maturation, and phagocytosis of the ligand.^[8]

Antifungal immunity

CLEC7A has been shown to recognize species of several fungal genera, including Saccharomyces, Candida, Pneumocystis, Coccidioides, Penicillium and others. Recognition of these organisms triggers many protective pathways, such as fungal uptake by phagocytosis and killing via respiratory burst. Activation of dectin-1 also triggers expression of many protecting antifungal cytokines and chemokines (TNF, CXCL2, IL-1b, IL-1a, CCL3, GM-CSF, G-CSF and IL-6) and the development of Th17.^[8]

Co-stimulatory molecule

Dectin-1 can also operate as a co-stimulatory molecule via recognition of an endogenous ligand on T-cells, which leads to cellular activation and proliferation. CLEC7A can bind both CD4+ and CD8+ T cells.^[8]

References

Further reading