CD283 TLR3 (Toll-like receptor 3)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Fibroblast
Dendritic Cell
Epithelial Cell
Pancreas
Placenta
Astrocyte
Microglia
100 / 100

Expression
CD283 is expressed on fibroblasts, epithelial and myeloid dendritic cells.  Expression is at high levels in placenta and pancreas.  It is detected in CD11c+ immature blood dendritic cells, microglia and astrocytes but not in other leukocytes including monocyte precursors.  Although CD283 is detectable on the cell surface, most CD283 is located intracellularly and is associated with endosomal compartments. Expression is also in breast milk.

Structure
MOLECULAR FAMILY NAME: Belongs to the Toll-like receptor family.

CD283 is a single-pass type-1 881 aa glycoprotein.  It contains a 23 aa signal sequence, a 681 aa extracellular domain which contains 22 leucine-rich repeats (LRR) capped at each end by N- and C-terminal motifs and has 11 potential N-linked glycosylation sites, a 21 aa transmembrane domain and an 179 aa cytoplasmic domain containing a Toll/IL-1R domain that interacts with the adaptor molecule Toll-IL1 receptor-resistance (TIR) and domain-containing adaptor inducing IFNβ (TRIF).  The LRRs form a "horseshoe-shaped structure which is the ligand-binding domain.  The extensive β-sheet on the protein's concave surface is the site of several modifications including insertions in the LRRs and 11 potential N-linked glycosylation sites.     

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD283 has 11 potential N-linked glycosylation sites.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD283

CD283 associates with double-stranded RNA.

Function
CD283 plays a fundamental role in pathogen recognition and activation of innate immunity.  TLRs are highly conserved from Drosophilia to humans and share structural and functional similarities.  They recognize pathogen-associated molecular patters (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity.  CD283 acts as a receptor which recognizes double-stranded RNA associated with the innate immune response to viral infection and pathogens and induces the activation of NF-κB and ERF3 to pro-inflammatory cytokine and type 1 IFN production.   CD283 acts via MyD88 and TRAF6, leading to NF-κB activation, cytokine secretion and the inflammatory response.  Activation of CD283 leads to the initiation of a caspase-dependent apoptotic cascade.  A role for CD283 in cross-presentation (presentation in association with MHC class I by cells not infected by the virus) and priming has been suggested for viruses that do not have tropism for dendritic cells.  This requires an uptake of antigen by ingestion of infected cells and CD283 (TLR3) appears to facilitate this process.


BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD283 IN INTACT ANIMAL

CD283 plays a role in the host response to viral infection.  It has been demonstrated that vaccinia virus and Hepatitis C virus (HCV) express proteins that target aspects of the CD283 signaling pathway and efficiently inhibit CD283-induced gene expression.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD283: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD283: No information.

ADDITIONAL INSIGHTS

For further information see Matsumoto, M. et al (2002) Biochem. Biophys. Res. Commun. 293: 1364-1369.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7098O15455
Antibodies

Revised June 25, 2008


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