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

View/Edit Human

View/Edit Mouse

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

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. "Entrez Gene: CLEC7A C-type lectin domain family 7, member A".
4. Drummond RA, Brown GD (2011). "The role of Dectin-1 in the host defence against fungal infections.". Curr Opin Microbiol. 14 (4): 392–9. doi:10.1016/j.mib.2011.07.001. PMID 21803640.
5. Brown J, O'Callaghan CA, Marshall AS, Gilbert RJ, Siebold C, Gordon S, Brown GD, Jones EY (2007). "Structure of the fungal beta-glucan-binding immune receptor dectin-1: implications for function.". Protein Sci. 16 (6): 1042–52. doi:10.1110/ps.072791207. PMC 2206667. PMID 17473009.
6. Taylor PR, Brown GD, Reid DM, Willment JA, Martinez-Pomares L, Gordon S, Wong SY (2002). "The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages.". J Immunol. 169 (7): 3876–82. doi:10.4049/jimmunol.169.7.3876. PMID 12244185.
7. Saijo S, Iwakura Y (2011). "Dectin-1 and Dectin-2 in innate immunity against fungi.". Int Immunol. 23 (8): 467–72. doi:10.1093/intimm/dxr046. PMID 21677049.
8. Huysamen C, Brown GD (2009). "The fungal pattern recognition receptor, Dectin-1, and the associated cluster of C-type lectin-like receptors.". FEMS Microbiol Lett. 290 (2): 121–8. doi:10.1111/j.1574-6968.2008.01418.x. PMC 2704933. PMID 19025564.

Further reading

• Drickamer K (1999). "C-type lectin-like domains". Curr. Opin. Struct. Biol. 9 (5): 585–90. doi:10.1016/S0959-440X(99)00009-3. PMID 10508765.
• Brown GD (2006). "Dectin-1: a signalling non-TLR pattern-recognition receptor". Nat. Rev. Immunol. 6 (1): 33–43. doi:10.1038/nri1745. PMID 16341139.
• Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence" (PDF). Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
• Ariizumi K, Shen GL, Shikano S, Xu S, Ritter R, Kumamoto T, Edelbaum D, Morita A, Bergstresser PR, Takashima A (2000). "Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning". J. Biol. Chem. 275 (26): 20157–67. doi:10.1074/jbc.M909512199. PMID 10779524.
• Yokota K, Takashima A, Bergstresser PR, Ariizumi K (2001). "Identification of a human homologue of the dendritic cell-associated C-type lectin-1, dectin-1". Gene. 272 (1–2): 51–60. doi:10.1016/S0378-1119(01)00528-5. PMID 11470510.
• Hermanz-Falcón P, Arce I, Roda-Navarro P, Fernández-Ruiz E (2001). "Cloning of human DECTIN-1, a novel C-type lectin-like receptor gene expressed on dendritic cells". Immunogenetics. 53 (4): 288–95. doi:10.1007/s002510100326. PMID 11491532.
• Brown GD, Gordon S (2001). "Immune recognition. A new receptor for beta-glucans". Nature. 413 (6851): 36–7. doi:10.1038/35092620. PMID 11544516.
• Willment JA, Gordon S, Brown GD (2001). "Characterization of the human beta -glucan receptor and its alternatively spliced isoforms". J. Biol. Chem. 276 (47): 43818–23. doi:10.1074/jbc.M107715200. PMID 11567029.
• Sobanov Y, Bernreiter A, Derdak S, Mechtcheriakova D, Schweighofer B, Düchler M, Kalthoff F, Hofer E (2002). "A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex". Eur. J. Immunol. 31 (12): 3493–503. doi:10.1002/1521-4141(200112)31:12<3493::AID-IMMU3493>3.0.CO;2-9. PMID 11745369.
• Grünebach F, Weck MM, Reichert J, Brossart P (2002). "Molecular and functional characterization of human Dectin-1". Exp. Hematol. 30 (11): 1309–15. doi:10.1016/S0301-472X(02)00928-1. PMID 12423684.
• Ahrén IL, Eriksson E, Egesten A, Riesbeck K (2003). "Nontypeable Haemophilus influenzae activates human eosinophils through beta-glucan receptors". Am. J. Respir. Cell Mol. Biol. 29 (5): 598–605. doi:10.1165/rcmb.2002-0138OC. PMID 12689921.
• Ebner S, Sharon N, Ben-Tal N (2003). "Evolutionary analysis reveals collective properties and specificity in the C-type lectin and lectin-like domain superfamily". Proteins. 53 (1): 44–55. doi:10.1002/prot.10440. PMID 12945048.
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A (2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Taylor PR, Brown GD, Herre J, Williams DL, Willment JA, Gordon S (2004). "The role of SIGNR1 and the beta-glucan receptor (dectin-1) in the nonopsonic recognition of yeast by specific macrophages". J. Immunol. 172 (2): 1157–62. doi:10.4049/jimmunol.172.2.1157. PMID 14707091.
• Mantegazza AR, Barrio MM, Moutel S, Bover L, Weck M, Brossart P, Teillaud JL, Mordoh J (2005). "CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells". Blood. 104 (4): 1183–90. doi:10.1182/blood-2004-01-0104. PMID 15130945.
• de la Rosa G, Yáñez-Mó M, Samaneigo R, Serrano-Gómez D, Martínez-Muñoz L, Fernández-Ruiz E, Longo N, Sánchez-Madrid F, Corbí AL, Sánchez-Mateos P (2005). "Regulated recruitment of DC-SIGN to cell-cell contact regions during zymosan-induced human dendritic cell aggregation". J. Leukoc. Biol. 77 (5): 699–709. doi:10.1189/jlb.0904529. PMID 15728245.
• Willment JA, Marshall AS, Reid DM, Williams DL, Wong SY, Gordon S, Brown GD (2005). "The human beta-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells". Eur. J. Immunol. 35 (5): 1539–47. doi:10.1002/eji.200425725. PMID 15816015.