DC-SIGN
Encyclopedia
DC-SIGN also known as CD209 (Cluster of Differentiation
209) is a protein
which in humans is encoded by the CD209 gene.
DC-SIGN is a C-type lectin
receptor present on both macrophages and dendritic cells. DC-SIGN on macrophages recognises and binds to mannose type carbohydrates, a class of Pathogen associated molecular patterns PAMPs commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis. On myeloid and pre-plasmacytoid dendritic cell
s DC-SIGN mediates dendritic cell rolling interactions with blood endothelium
and activation of CD4
+ T cell
s, as well as recognition of pathogen
haptens.
molecule. It binds various microorganisms by recognizing high-mannose
-containing glycoprotein
s on their envelopes and especially functions as receptor for several viruses such as HIV
and Hepatitis C
. Binding to DC-SIGN can promote HIV and Hepatitis C virus to infect T-cell from dendritic cells. Thus binding to DC-SIGN is an essential process for HIV infection. Besides functioning as an adhesion
molecule, recently some study has also shown that DC-SIGN can initiate innate immunity by modulating toll-like receptor
s. But the detailed mechanism is not known yet. DC-SIGN together with other C-type lectins is involved in recognition of tumors by dendritic cells. And DC-SIGN is a potential engineering target for dendritic cell based cancer vaccine.
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 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 T cells by interaction between DC-SIGN and ICAM-3.
s and eukaryote
s 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 receptor
s) 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
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.
Cluster of differentiation
The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules present on white blood cells, providing targets for immunophenotyping of cells...
209) is a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the CD209 gene.
DC-SIGN is a C-type lectin
C-type lectin
A C-type lectin is a type of carbohydrate-binding protein domain known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and...
receptor present on both macrophages and dendritic cells. DC-SIGN on macrophages recognises and binds to mannose type carbohydrates, a class of Pathogen associated molecular patterns PAMPs commonly found on viruses, bacteria and fungi. This binding interaction activates phagocytosis. On myeloid and pre-plasmacytoid dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s DC-SIGN mediates dendritic cell rolling interactions with blood endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
and activation of CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
+ T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s, as well as recognition of pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
haptens.
Function
DC-SIGN is a C-type lectin and has a high affinity for the ICAM3ICAM3
Intercellular adhesion molecule 3 also known as CD50 , is a human gene.-Interactions:ICAM3 has been shown to interact with EZR and Moesin.-Further reading:...
molecule. It binds various microorganisms by recognizing high-mannose
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
-containing glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
s on their envelopes and especially functions as receptor for several viruses such as HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and Hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
. Binding to DC-SIGN can promote HIV and Hepatitis C virus to infect T-cell from dendritic cells. Thus binding to DC-SIGN is an essential process for HIV infection. Besides functioning as an adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
molecule, recently some study has also shown that DC-SIGN can initiate innate immunity by modulating toll-like receptor
Toll-like receptor
Toll-like receptors are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors that recognize structurally conserved molecules derived from microbes...
s. But the detailed mechanism is not known yet. DC-SIGN together with other C-type lectins is involved in recognition of tumors by dendritic cells. And DC-SIGN is a potential engineering target for dendritic cell based cancer vaccine.
Role in HIV infection
This moleculeMolecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
is involved in the initial stages of the human immunodeficiency virus
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
infection, as the HIV gp120
Gp120
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons...
molecule causes co-internalization of the DC-SIGN molecule and HIV 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 T cells by interaction between DC-SIGN and ICAM-3.
Gene family
DC-SIGN/CD209 is an animal "C-lectin", a large and diverse family of proteins found in both prokaryoteProkaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s and eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s most of which are functional lectins, meaning they bind carbohydrate ligands
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
, and whose ligand-binding affinity requires calcium (hence "C-lectin"). Among the animal C-lectins, a subfamily known as the ASGR (asialoglycoprotein receptor
Asialoglycoprotein receptor
The asialoglycoprotein receptors are lectins which bind asialoglycoprotein, glycoproteins from which a sialic acid has been removed to expose galactose residues. The receptors, which are located on liver cells, remove the target glycoproteins from circulation....
s) 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
CD23
CD23, also known as Fc epsilon RII, or FcεRII, is the "low-affinity" receptor for IgE, an antibody isotype involved in allergy and resistance to parasites, and is important in regulation of IgE levels. Unlike many of the antibody receptors, CD23 is a C-type lectin...
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
CLEC4M
C-type lectin domain family 4 member M is a protein that in humans is encoded by the CLEC4M gene. CLEC4M has also been designated as CD299 .-Further reading:...
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.