CD299 CLEC4M (C-type lectin domain family 4, member M),   DC-SIGNR (DC-SIGN-related), L-SIGN, DC-SIGN2, CD209L (CD209 antigen-like)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 2 glycoprotein
Endothelial Cell
Lymph Node
Liver
Lung
Placenta
Endothelium
40 / 40

Expression
CD299 is highly expressed in liver sinusoidal endothelial cell subsets and by endothelial cells present beneath the subcapsular sinus of lymph nodes, placental endothelium as well as in type-2 aveolar cells and lung endothelial cells. Expressiuon is not found in macrophages. 


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

CD299 is a single-pass type-2 399 aa integral glycoprotein.  It contains a 329 extracellular domain which contains an 117 aa C-terminal C-type lectin domain, 7 23 aa  tandem repeats which are required for the formation of tetramers, 2 potential N-linked glycosylation sites and 6 calcium binding sites, a 21 aa transmembrane domain and 43 aa intracellular N-terminal cytoplasmic domain which contains a triacidic cluster and a di-leucine motif which are potential internalization motifs.  The protein is 77% identical to the CD209 antigen, a HIV gp120-binding protein, and certainly arisen as a result of gene duplications.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative spicing yields 11 different isoforms.  Four of the isoforms (5, 6, 7, and 10) are potentially secreted.

POST-TRANSLATIONAL MODIFICATION: No information.

CD299 has 2 potential N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD299

CD299 binds CD50 (ICAM-3) and high mannose moiteties of carbohydrate structures of several pathogens such as lentiviruses (HIV-1 and Ebola virus), human cytomegalovirus, Hepatitis C virus and SARS coronavirus, as well as Mycobacterium tuberculosis.

Function
CD299 is probably a pathogen recognition receptor involved in peripheral immune surveillance in the liver and may mediate the endocytosis of pathogens which are subsequently degraded in lysosomal compartments.  It has yet to be demonstrated whether CD299 induces tolerogenic responses in liver sinusoidal endothelial cells and lymph node endothelial cells.  Like CD209, CD299 recognizes Ca2+ dependent manner high mannose N-linked oligosaccharides in a variety of pathogen antigens including HIV-1 gp120 and appears to mediate endocytosis of pathogens which are subsequently degraded in lysosomal compartments.  CD299 mediates interactions between dendritic cells and resting T cells and has a high affinity for HIV-1 gp120.  CD299, like CD209, efficiently binds both intercellular adhesion molecule 3 CD50 (ICAM3) and HIV-1 gp120, and enhances HIV-1 infection to permissive T cells.  Binding to CD299 is not reversible which suggests the receptor is not recycled after endocytosis but is degraded within endosomes or lysosomes.  CD299 mediates interactions between dendritic cells and resting T cells and has a high affinity for HIV-1 gp120.  

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD299 IN INTACT ANIMAL

CD299 is a receptor for CD50, probably by binding mannose-like carbohydrates and is presumably a coreceptor for SARS coronavirus S protein.  It has been demonstrated in vitro that CD299 can mediate in trans-delivery of several viruses, including Ebola virus and Sindbis use CD299 as a portal of entry and HIV-1 and hepatitis C virus can bind to CD299 on cell membranes but do not use it to mediate virus entry.  Its physiological function is unknown but it may play a role in the interaction between the liver sinusoidal endothelium and trafficking lymphocytes as well as function in the pathogenesis of HIV-1.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD299: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD299: No information.

ADDITIONAL INSIGHTS

For further information see Bashirova, A. A. et al (2001) J. Exp. Med. 193: 671-678.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene10332Q9H2X3
Antibodies

Revised June 25, 2008


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