CD284 TLR4 (Toll-like receptor 4)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
Macrophage
Endothelial Cell
Dendritic Cell
Myelomonocytic cell
T Cell
Spleen
Placenta
Granulocyte
Leukocyte
Peripheral blood
85 / 85

Expression
CD284 is expressed on monocytes, dendritic cells, macrophages, granulocytes, endothelial cells and activated T cells.  There is high expression in placenta, spleen myelomonocytic subpopulation of leukocytes and peripheral blood leukocytes, but expression is weak on immature dendritic cells and neutrophils.  Expression is also in breast milk.

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

CD284 is a single-pass type-1 816 aa glycoprotein.  It contains a 23 aa signal sequence, a 608 aa extracellular domain which contains 21 leucine-rich repeats (LRRs) capped at the N- and C-terminal motifs and has 10 potential N-linked glycosylation sites, a 21 aa transmembrane domain and an 187 aa intracellular cytoplasmic domain which contains a Toll/IL-1R domain that interacts with the adaptor molecules TIR domain-containing adaptor protein (TIRAP)  and TRIF-related adaptor molecule (TRAM). The LRRs forms a "horseshoe" shaped form which is the ligand-binding domain.  CD284 forms a complex with the MD2 (Ly96) adaptor protein.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Several transcript isoforms have been found but the protein coding of most of them is uncertain.

POST-TRANSLATIONAL MODIFICATION

CD284 has 10 N-glycosylated sites.  Glycosylation of Ans-526 and Ans-575 seem to be necessary for the expression of CD284 on the cell surface and the lipopolysaccharide-response.  Likewise,  lacking two or more of the other N-glycosylation sites mutants are deficient in interaction with LPS.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD284

CD284 binds lipopolysaccharide (LPS) and may be involved in the binding of endogenous ligands such as heat shock proteins Hsp60 and Hsp70 and fibrinogen.  However, CD284 binding of endogenous ligands has not been clearly established. 


Function
CD284 belongs to the lipopolysaccharide receptor and cooperates with CD14, and MD2 (LY96) to mediate innate immune response to bacterial LPS.  It binds LY96 via the extracellular domain and recruits TIRAP and TRAM which activates myeloid differentiation primary response gene 88 (MyD88)- dependent and MyD88-independent (TRIF-dependent) signaling pathways via their respective TIR domains.  Activation of both of these pathways is essential for inducing inflammatory cytokine production and favors a Th1 response.  CD284 leads to NF-κB activation, cytokine secretion and the inflammatory response.  The receptor has been  implicated in signal transduction events induced by lipopolysaccharide found in most Gram-negative bacteria.  LPS-activated CD284 can induce dendritic cell maturation via TRIF-dependent signaling.  CD284 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.  

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD284 IN INTACT ANIMAL

Mutations in CD284 are associated with differences in LPS responsiveness.  CD284-deficient mice are more susceptible to a number of Gram-negative and Gram-positive bacterial pathogens and fungal pathogens.  CD284 recognizes the fusion protein of respiratory syncytial virus (RSV) and the fungal pathogens Aspergillus fumigatus and Candida albicans.  Increased susceptibility was found to be the result of decreased neutrophil recruitment to the site of infection because of defective chemokine production and decreased chemokine receptor expression.  There have been several small studies of the impact of single nucleotidepolymorphisms of CD284 on susceptibility to infectiious and inflammatory diseases.  Larger studies are needed as the generally small numbers of partcipants and conflicting results make it impossible to draw any conclusions at this time. 

Comments

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD284: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD284: No information.

ADDITIONAL INSIGHTS

For further information see Jiang, Q. et al (2000) J. Immunol. 165: 3541-3544.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 7099O00206
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