|CD208||LAMP3 (lysosomal-associated membrane protein 3, DC-LAMP (dendritic cell lysosome-associated membrane protein)|
|Molecule Type||Antigen Expression||Molecular Weight|
Min / Max
|Lineage Restricted Molecule|
Type 1 glycoprotein
|70 / 70|
79 / 79
|CD208 is expressed and is restricted to activated dendritic cells. While undetected in immature dendritic cells, CD208 is sharply expressed upon activation with LPS, TNFa or CD40L in dendritic cells isolated from skin-purified Langerhans cells, CD11c+ and CD11c- tonsil dendritic cells, dendritic cells generated in cultures of CD34+ cells in the presence of GM-CSF+ TNFa and from monocytes cultures with GM-CSF and IL-4. PMA ionomycin activated macrophages, LPS activated monocytes and CD40L activated B cells also weakly express CD208 mRNA. Lysosomal distribution of the protein is found in the MHC class II compartment immediately before the translocation of the MHC II molecules to the cell surface. Within the tonsil, spleen and lymph node, CD208 is exclusively observed in large cells present in T cell areas which co-express CD83 and a high level of CD40 which represents interdigitating dendritic cells. None of the CD68+ cells, tingible body macrophages and a few macrophages found in T cell areas, or the germinal center dendritic cells present in germinal centers co-express CD208. CD208 cells were detected in the thymus medullar, cortical dendritic cells, in the small intestine in the T cell areas corresponding to Peyer's patches and occassionally in the dermis. In breast carcinoma tissue, while immature dendritic cells are found within the tumor bed, mature CD208 dendritic cells are confined to peritumoral areas. Expression is also found in lymphoid organs, the lung, and upregulated in carcinomas of the esophagus, colon, rectum, ureter, stomach, fallopian tubes, thyroid and parotid tissues.|
|MOLECULAR FAMILY NAME: Belongs to the lysosomal associated membrane protein family.|
CD208 is a single-pass type-1 416 aa glycoprotein. It contains a 21aa signal sequence, a 381 aa extracellular domain which contains 2 potential disulphide bonds, 7 N-glycosylation sites and several O-glycosylation sites with the potential for extensive O-glycosylation to form mucin, a 25 aa hydrophobic transmembrane and a 10 aa short cytoplasmic domain which has a glycine-tyrosine lysosome-targeting motif common to all LAMP members. CD208 is comprised of a full length 3155 bp cDNA sequence having a 1248 bp open reading frame encoding a type 1 integral membrane protein.
POST-TRANSCRIPTIONAL MODIFICATION: No information.
There is a sequence indicating 7 potential N-glycosylation sites, Asn-X-Ser/Thr, and several O-glycosylation sites. CD208 has a short cytoplasmic tail with a glycine-tyrosine motif which characterizes all known LAMP family members. The predicted aa sequence shows the closest homology 29% with human CD28, 23% with human LAMP-1 and 21% with LAMP-2. The intra-luminal portion of CD208 and CD68 has 2 domains separated by a serine/proline-rich hinge region. The N-terminal domain has several serine, threonine and proline residues which may contribute a mucin-like portion covered with O-linked glycans. The membrane proximal domain contains 4 cysteines and probably 2 disulfide bounds.
| LIGANDS AND MOLECULES ASSOCIATED WITH CD208: No information.|
|CD208 is transiently expressed by dendritic cells at the limiting membrane of MHC class II containing intracellular compartments. With further maturation, CD208 becomes concentrated in perinuclear lysosomes which changes the lysosome function after the transfer of peptide loading onto MHC class II molecules to the surface of dentritic cells. CD208 first appeared in the lysosomal MHC class II compartment (MIIC), which was initially described in human B cells and more recently in immature dendritic cells. The MIIC is thought to be the site of efficient peptide loading on the MHC class II molecules in human B cells. The appearance of CD208 parallels and may participate to the remodeling of the endosome/lysosome compartment observed during human dendritic cells maturation. The lysosome targeting motif is recognized by adaptor complexes AP1, AP2 and AP3 which transport CD208 from the trans-Golgi network to the lysosomal membrane. It is proposed that CD208 plays a role in sorting MHC class II membrane associated molecules and therefore is important in the processing of exogenous antigens.|
BIOCHEMICAL ACTIVITY: No information.
DISEASE RELEVANCE AND FUNCTION OF CD208 IN INTACT ANIMAL: No information.
|MOLECULAR INTERACTIONS -|
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD208: No information.
SUBSTRATES: No information.
ENZYMES WHICH MODIFY CD208: No information.
Database accession numbers
Revised June 25, 2008