CD206 MCR1 (mannose receptor, C type 1), MMR (macrophage mannose receptor)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Macrophage
Dendritic Cell
Plasma Cell
Placenta
Endothelial Cell
162 / 162
175 / 175

Expression
CD206, the mannose receptor (MMR), is strongly expressed by subsets of mononuclear phagocytes but not on circulating monocytes.  It is expressed by hepatic and lymphatic endothelial cells, immature dendritic cells, on mature tissue macrophages and cells in the placenta.  There is expression by retinal pigmental epithelium (RPE), mesangial cells and is modulated by TH1 and TH2 cytokines in activated macrophages.  CD206 is also found in the plasma membrane, endosomes, ER and Golgi during synthesis and lysosomes before degradation.  It is expressed on some dendritic epidermal cells. Its expression on macrophages is upregulated in response to IL-4, IL-3 or anti-inflammatory steroids and downregulated by IFNg or IFNa

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

CD206 is single-pass type-1 glycoprotein.  It contains an extracellular domain which contains a N-terminus with a Cys-rich domain that shows a sequence similarity to a ricin B-type lectin domain, a fibronectin type-2 domain, 8 C-type lectin carbohydrate domains, a transmembrane domain and a short cytoplasmic domainl that completes the C-terminal intracellular domain.  CD206 is a mannose receptor and belongs to the pattern recognition family of receptors.  The cDNA is comprised of 1456 aa with a predicted Mr of 16,600 protein.  The overall molecular organization of the MMR is similar to that of the M-type receptor for secretory phospholipases A2, DEC-205 and a 4th, widely expressed, member of this C-type lectin family.

MOLECULAR MASS
Cell Type Unreduced Reduced
Macrophages 162 kDa
Retinal pigment epithelium 162 kDa - 175 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD206 undergoes early proteolytic processing to remove the signal peptide, undergoes N- and O-linked glycosylation and might undergo ligand activated proteolytic cleavage to generate a soluble form.


Ligands
CD206 binds oligomannose-containing carbohydrates.  In addition, the Cys-rich domain of the mouse MMR, fused to the Fc region of human IgG1, binds to macrophage populations in the splenic marginal zone, metallophilic macrophages, and the lymph node subcapsular sinus.  The ligand(s) for the Cys-rich domains is also expressed in germinal centers of the spleen and follicular areas of lymph nodes in immunized mice.  It associates with mannosylated Ag.
 
LIGANDS AND MOLECULES ASSOCIATED WITH CD206
Molecule Comment
Lysosomal b-glucuronidase
Plant glycoproteins horseradish peroxidase
Yeast proteins mannan, invertase
Neoglycoproteins mannose25 - BSA
Chitin
Bacterial cell wall molecules
Viral glycoproteins HIV gp120
Glycoforms of CD169 and CD45
Lutropin
Chondroitin-4-sulfate


Function
CD206 functions as an antigen receptor that mediates endocytosis and phagocytosis by mononuclear phagocytes.  Its function contributes to innate and acquired immunity.  The two distinct extracellular lectin binding sites have different binding specificities.  The cysteine-rich domain is known to bind sulphated sugars present in anterior pituitary derived glycoprotein hormones and sulfated glycoforms of CD169 and CD45 found in specialized macrophage subpopulations.  The second lectin-like activity is mediated by several of its eight carbohydrate recognition domains (CRD) and show preference for branched sugars with terminal mannose, fucose N-acetylglucosamine or glucose residues.  CD206 binds oligo-mannose-containing molecules and mediates phagocytosis by macrophages of microorganisms with cell walls containing oligomannose carbohydrates.  Presentation  of mannose-bearing antigens to T cells in vitro is improved in the presence of cultured CD206 hi dendritic cells.  The protein has been shown to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria and fungi so that they can be neutralized by phagocytic engulfment.  This suggests CD206 has a role in acquired immune responses.  It may slo be involved in the uptake of rod outer segment proteins by retinal pigment epithelium.  COS-1 cells transfected with the full length MMR cDNA bind and internalize Candida albicans yeast particles.  Cell transfected with a cDNA mutated to delete the cytoplasmic region express the protein, but do not ingest particles.  CD206 binds both sulfated and non-sulfate polysaccharide chains. 

BIOCHEMICAL ACTIVITY

There is no known biochemical activity other than binding to glycans and sulphated sugars

DISEASE RELEVANCE AND FUNCTION OF CD206 IN INTACT ANIMAL

CD206 mediates recognition and internalization via oligosaccharide domains that are present in gram-positive and gram-negative bacteria, mycobacteria and yeast.  This is likely to be important in the host innate immune response.  A role is played in the induction of the acquired immune responses which is suggested by high levels of expression in cultured human dendritic cells that are correlated with enhanced presentation of mannosylated molecules to T cells.  Endogenous ligands for CD206 have been characterized.  For example, CRDs of CD206 mediate binding to neutrophils derived myeloperoxidase, tissue plasminogen activator and lysosomal hydrolases.  Cysteine-rich domains sulphate sugars present in hormones such as lutropin and chondroitin sulfates A and B which are present on proteoglycans in the extracellular matrices.  Also sulfated glucoforms of sialoadhesin (CD169) and CD45 are expressed by specialized macrophage subpopulations in secondary organs.  Another potential role for CD206 is in the phagocytic uptake of rod outer segment proteins by the retinal pigment epithelium.  The data indicate that apart from a potential role in the immune response, CD206 might be an important player in homeostatasis.


Comments
The human CD206 gene is divided into 30 exons.  CD206 has 3 molecular pathways, endocytic, phagocytic and antigen presentation pathways. 

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD206: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD206: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 4360P22897
MouseA48925Z11974
Antibodies
19.2   View Reactivity

Revised June 25, 2008


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