DC-SIGN

CD209
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1K9I, 1SL4, 1SL5, 2B6B, 2IT5, 2IT6, 2XR5, 2XR6
Identifiers
Aliases	CD209, CDSIGN, CLEC4L, DC-SIGN, DC-SIGN1, CD209 molecule, hDC-SIGN
External IDs	OMIM: 604672 MGI: 2157948 HomoloGene: 128353 GeneCards: CD209
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.2 Start 7,739,993 bp[1] End 7,747,564 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 A1.1 Start 3,897,965 bp[2] End 3,904,309 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lymph node superficial temporal artery rectum right coronary artery jejunal mucosa gallbladder duodenum synovial joint appendix subcutaneous adipose tissue Top expressed in morula skin of abdomen lip thymus blastocyst skin of back white adipose tissue subcutaneous adipose tissue diencephalon pituitary gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptide antigen binding virus receptor activity metal ion binding protein binding mannose binding virion binding carbohydrate binding Cellular component cytoplasm integral component of membrane membrane extracellular region cell surface extracellular exosome external side of plasma membrane host cell plasma membrane Biological process leukocyte cell-cell adhesion cell-cell recognition intracellular transport of virus regulation of T cell proliferation heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules intracellular signal transduction antigen processing and presentation endocytosis adaptive immune response immune system process viral genome replication stimulatory C-type lectin receptor signaling pathway peptide antigen transport cell adhesion modulation by virus of host process viral entry into host cell viral process virion attachment to host cell innate immune response positive regulation of T cell proliferation B cell adhesion Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 30835 170780 Ensembl ENSG00000090659 ENSMUSG00000040197 UniProt Q9NNX6 Q91ZW7 RefSeq (mRNA) NM_001144893 NM_001144894 NM_001144895 NM_001144896 NM_001144897 NM_001144899 NM_021155 NM_130905 RefSeq (protein) NP_001138365 NP_001138366 NP_001138367 NP_001138368 NP_001138369 NP_001138371 NP_066978 NP_570975 Location (UCSC) Chr 19: 7.74 – 7.75 Mb Chr 8: 3.9 – 3.9 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 (Cluster of Differentiation 209) is a protein which in humans is encoded by the CD209 gene.^[5]

DC-SIGN is a C-type lectin receptor present on the surface of both macrophages and dendritic cells. DC-SIGN on macrophages recognises and binds with high affinity to high-mannose type N-glycans, a class of PAMPs (pathogen associated molecular patterns) commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis.^[6] On myeloid and pre-plasmacytoid dendritic cells DC-SIGN mediates dendritic cell rolling interactions with blood endothelium and activation of CD4+ T cells, as well as recognition of pathogen haptens.

Function

DC-SIGN is a C-type lectin and has a high affinity for the ICAM3 molecule.^[7] It binds various microorganisms by recognizing high-mannose-containing glycoproteins on their surface, and can function as a co-receptor for several viruses such as HIV and Hepatitis C.^[8][9][10] Binding to DC-SIGN can promote HIV and Hepatitis C virus to infect target cells (T-cells and hepatocytes, respectively).^[9][10]

Besides functioning as an adhesion molecule, recent studies have also shown that DC-SIGN can initiate innate immunity by modulating toll-like receptors,^[11] though the detailed mechanism is not yet known. DC-SIGN together with other C-type lectins is involved in recognition of tumors by dendritic cells. DC-SIGN is also a potential engineering target for dendritic cell based cancer vaccine.^[12]

Clinical significance

HIV infection

This molecule is involved in the initial stages of the human immunodeficiency virus infection, as the HIV gp120 molecule causes co-internalization of the DC-SIGN molecule and HIV virus particle (virion). The dendritic cell then migrates to the cognate lymphoid organ, whereupon recycling of the DC-SIGN/HIV virion complex to the cell periphery facilitates HIV infection of CD4⁺ T cells by interaction between DC-SIGN and ICAM-3.^[13]

Ebola infection

Different studies have demonstrated that the ebola virus infection process starts when the virus reaches the cellular DC-SIGN receptor to infect the dendritic cells (of the immune system). In 2015 European researchers designed a “giant” molecule formed by thirteen fullerenes covered by carbohydrates which, by blocking DC-SIGN receptor, are able to inhibit the cell infection by an artificial ebola virus model. These antiviral molecules decorated with specific carbohydrates (sugars) present affinity by the receptor used as an entry point to infect the cell and act blocking it, thus inhibiting the infection in a sub-nanomolar range.^[14]

SARS-CoV-2

DC-sign and its counterpart L-SIGN (CD 209L) have also been identified as receptors facilitating the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into human cells. Significant CD209L expression has been revealed in lung and kidney epithelia and endothelia and interactions with SARS-CoV-2 Spike protein (S protein) have been demonstrated in vitro.^[15][16] CD209L also exhibits interaction with Angiotensin-converting enzyme-2 (ACE2), suggesting a potential role for CD209L-ACE2 heterodimerization in SARS-CoV-2 entry and infection in cell types expressing both proteins.^[17] It is shown that DC/L-SIGN can enhance viral infection and dissemination by contributing to additional routes of infection mediated by the S protein in a process called trans-infection.^[18] This process seems to be exclusive for DC/L-sign interaction. This complexity in the recognition patterns and functions of these receptors is similar to what has been observed in other viruses like HIV and ebola virus.

Gene family

DC-SIGN/CD209 is an animal "C-lectin", a large and diverse family of proteins found in both prokaryotes and eukaryotes most of which are functional lectins, meaning they bind carbohydrate ligands, and whose ligand-binding affinity requires calcium (hence "C-lectin"). Among the animal C-lectins, a subfamily known as the ASGR (asialoglycoprotein receptors) group contains several sub-sub-families, many of which are important to innate immunity.

A cluster of genes in both humans and mice contains three related members of the "DC Receptor" class, so named because of their homology to DC-SIGN. Of these, CD23 is, however, not expressed on dendritic cells but is a characteristic surface molecule of B lymphocytes, and LSectin (CLEC4G) is expressed on the sinusoidal endothelium of the liver. The third gene group consists of multiple paralogues of CD209. Thus, both primates and mice have multiple paralogues of CD209 more closely related to each other within the species than to their orthologous counterparts in the other species. Higher primates have at least three DC-SIGN genes, DC-SIGN, DC-SIGNL1 (also known as DC-SIGNR or L-SIGN^[19]) and DC-SIGNL2, although not all three are present in every species; DC-SIGNL2 has not been detected in humans. Eight paralogous of DC-SIGN have been reported in the laboratory mouse strain C57BL/6; these go by the names DC-SIGN, DC-SIGNR2...DC-SIGNR8. DC-SIGNR6 is a pseudogene. The genes labeled "DC-SIGN" in the human and mouse are thus not unique orthologues, although they resemble each other functionally and by being expressed on dendritic cells. Other members of the mouse CD209 gene group are differentially expressed on different cell types. For example, DC-SIGNR1 is expressed largely on macrophages in the marginal zones of the spleen and in the medulla of lymph nodes.^[20]

References

Further reading

External links

• DC-SIGN at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.