CD280 MRC2 (mannose receptor, C type 2), UPARAP, TEM22, MRC2,  KIAA0709
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Myeloid Progenitor Cell
Fibroblast
Macrophage
Endothelial Cell
Osteoclast
Chondrocyte
Lung
Kidney
Osteocyte
Mesenchymal Cell
160 / 160
170 / 170

Expression
CD280 is expressed on myeloid progenitor cells, fibroblasts, chondrocytes, osteoclasts, osteocytes and subsets of endothelial and macrophage cells and by mesenchymal cells at sites of active tissue remodeling, including the progression of carcinomas.  The expression is ubiquitous with low expression in brain, placenta, lung, kidney, pancreas, spleen, thymus and colon.  There is a high expression in fetal lung and kidney.

Structure
MOLECULAR FAMILY NAME: Belongs to the macrophage mannose receptor protein family.

CD280 is a single-pass type-1 glycoprotein.  It contains a N-terminal signal sequence, 10 extracellular domains which contains a N-terminal cysteine-rich domain,  8 C-type lectin-like domains, a fibronectin type-II domain and a ricin B-type lectin domain (cysteine-rich domain with structural similarity to soybean trysin inhibitor), a transmembrane domain and a short cytoplasmic domain.  The C-type lectin domains 3 to 8 are not required for calcium-dependent binding of mannose, fucose and N-acetylglucosamine.  C-type domain 2 is responsible for sugar-binding in a calcium-dependent manner.  The fibonectin type-II domain mediates collagen-binding and ricin B-type lectin domain contacts with the second C-type lectin domain.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD280 is phosphorylated.  Deglycosylation reduces the molecular weight to 160-170 kDa, indicating that CD280 is N-glycosylated.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD280

CD280 binds gelatin and collagen types I, II, IV and V.

Function
CD280 is a constitutively recycled cell surface adhesion molecule that binds extracellular matrix (ECM) proteins and mediates their uptake and lysosomal degradation.  CD280 forms a complex with urokinase plasminogen activator (uPA) and its receptor, CD87, and this complex may play a role in CD87-dependent cell migration.  The addition of uPA to MDA-MB-231 breast cancer cells resulted in clustering of CD280 and CD87 at the leading edge of the polarized cells and increased cell motility.  This effect could be abolished by pre-treating the cells with CD280-specific small interfering RNA.  CD280 may play a role as endocytotic lectin receptor displaying calcium-dependent lectin activity.  It internalizes glycosylated ligands from the extracellular space for release in an endosomal compartment via cathrin-mediated endocytosis.  Involvement may be in plasminogen activiation system controlling the extracellular level of PLAUR/PLAU and thus may regulate protease activity at the cell surface. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD280 IN INTACT ANIMAL

CD280 is a potential therapeutic target in the treatment of carcinomas by limiting ECM degration and tumor progression.  CD280 expression is not detectable in human breast cancer cells but is present in tumor-associated stromal cells.  In a murine model of human ductal mammary adenocarcinoma, tumor-associated stromal cells were shown to internalize and degrade collagen in a CD280-dependent process.  CD280 may play a role during cancer progression as well as in other chronic tissue destructive diseases acting on collagen turnover. CD280 may contribute to cellular uptake, remodelling and degration of the extracellular collagen matrices.  When these tumors were generated in CD280 deficient mice, which are phenotypically normal, collagen turnover was abrogated and the tumors were fibrotic and smaller than the tumors generated in CD280 +/+ mice.  CD280 expression has been also reported at sites of non-neoplastic tissue degenerative disease such as osteoarthritis, rheumatoid arthritis,emphysema and periodontal disease.



Comments

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD280: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD280: No information.

ADDITIONAL INSIGHTS

For further information see Wienke, D. et al (2003) Mol. Biol. Cell 14: 3592-3604.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 9902Q9UBG0
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University