CD209 DC-SIGN (Dendritic cell-specific ICAM-3)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 2 glycoprotein
Dendritic Cell
Macrophage
Tonsil
Spleen
Endothelial Cell
Skin
44 / 44

Expression
CD209 is predominantly expressed on immature dendritic cells at dermal and mucosal sites and on immature and mature dendritic cells in lymphoid tissues as well as a subset of CD14+ dendritic-like cells found in blood placental macrophages and endothelial cells of placental vascular channels.  Expression is found in placental macrophages, endothelial cells of placental vascular channels and in THP-1 monocytes.  It is not expressed on T and B cells, granulocytes, or thymocytes.  CD209 recognizes dendritic-like cells present in the T cell area of the tonsil and spleen and stained dermal dendritic cells in the skin.  Expression is very low, 4% of PBMC consisting of CD14+ cells but is not found on CD11b- and CD14-blood dendritic cells even after activation, Langerhans cells of the skin or follicular dendritic cells in germinal centers of the tonsil.  Expression is high on dendritic-like cells in various mucosal tissues. 

Structure
MOLECULAR FAMILY NAME: Belongs to the C-type lectin superfamily.

CD209 is a single-pass type-2 404 aa glycoprotein.  It contains an 346 aa extracellular domain which contains an 126 aa C-type lectin domain, 7 complete and 1 incomplete tandem repeats of an 11 aa sequence which mediated the formation of tetramers, 6 calcium binding sites, 1 potential N-linked glycosylation and 3 disulphide bonds, a 21 aa transmembrane domain and a 37 aa N-terminal intracellular cytoplasmic domain that contains a dileucine motif essential for internalization as well as a triacidic cluster and tyrosine-based motif which are potential internalization motifs.  Tetramers have been shown to aggregate into well-organized micro-domains on the dendritic cell surface.  CD209 binds to ICAM-3 and CD50.  Originally it was described as a molecule which binds to gp120 on HIV but now has been discovered to identify ligands for ICAM-3 on T lymphocytes.  CD209 has a cDNA sequence of 1237 nucleotides and is identical to the HIV-1 gp binding C-type lectin.  The extracellular C-terminal region shows homology to mannose binding Ca2+ -dependent C-type lectins and contains a Ca2+ recognition domain (CRD) that is involved in the orientation of Ca2+ for mannose binding.

MOLECULAR MASS
Cell Type Unreduced Reduced
Immature dendritic cell 44 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 13 different isoforms.  Isoforms 1-5 are single-pass type 2 glycoproteins and isoforms 6-13 are secreted proteins.
 
POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD209

CD209 binds CD50 (ICAM-3) and CD102 (ICAM-2) with high affinity.  It also associates with mannose glycoproteins.

Function
The C- type lectin receptors, CD209, are involved in the primary interface between host and pathogens.  Two prototypic members of this receptor family act as both cell-adhesion receptors and pathogen-recognition receptors: CD209 and a close relative CD209L.  The initial interaction between these receptors is translated into a set of endogenous signals that ultimately lead to the induction of the adaptive immune response.  The pathogen-recognition receptor is expressed on the surface of immature dendritic cells and is involved in the initiation of primary immune response.  It is thought to mediate endocytosis of pathogens which are subsequently degraded in lysosomal compartments. 

CD209 binds the mannose-like carbohydrate CD50 (ICAM-3) and CD102 (ICAM-2).  Ligation with CD50 on T cells appears to regulate dendritic-induced T-cell proliferation and interaction with CD102 may enable dendritic cell rolling and transendothelial migration from blood to tissues.  The EPN motif in the lectin domain predicts mannose-binding specificity and it is probable that attachment of a variety of pathogens to immature dendritic cells is mediated via CD209 Ca2+-dependent recognition of high mannose N-linked carbohydrates.  This interaction leads to endocytosis of pathogens and their subsequent degradation in lysosomal compartments.  CD209 is recycled to the cell surface, whereas pathogen-derived antigens are presented to reating T cells via MHC class II proteins to initiate an adaptive immune response.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD209 IN INTACT ANIMAL

CD209 acts as a receptor and is recognized in a calcium-dependent manner high mannose N-linked oligosaccharide in a variety of pathogen antigens such as Ebola virus, human cytomegalovirus, Hepatitis C virus, Leishmania, Mycobacterium tuberculosis, H. pyloria, HIV-1 gp120 and other diseases.  Entry of pathogens via CD209 has the potential to enable transport of pathogens to other cellular targets as in the case of HIV.   CD209 expressed on dendritic cells captures HIV-1 at the periphery through a high affinity gp120 binding and transports the HIV-1 to lymphoid tissues.  Not all endocytosed viral particles are degraded but can be presented to T cells mediating infection in trans-mechanism. 




Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD209: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD209: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene30835Q9NNX6
Antibodies
120507   View Reactivity
DCN46   View Reactivity

Revised June 25, 2008


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