CD289 TLR9 (Toll-like receptor 9)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Dendritic Cell
B Cell
Lymph Node
Spleen
Tonsil
Liver
Lung
Bone Marrow
115 / 115
120 / 120

Expression
CD289 is expressed on activated B cells and intracellular and plasmacytoid dendritic cell subsets.  There is high expression in spleen, lymph node, tonsil, bone marrow but there are lower levels in monocytes, peripheral blood leukocytes and CD11c+ immature dendritic cells.  Expression is also detected in lung and liver. 

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

CD289 is a single-pass type-1 glycoprotein.  It contains a 25 aa signal sequence, an 1007 aa extracellular domain which contains 26 leucine-rich repeats (LRR) capped at each end by N- and C-terminal motifs, a 21 aa transmembrane domain and an 193 aa intracellular cytoplasmic domain which contains a Toll/IL-1R domain that interacts with the adaptor molecule myeloid differentiation primary response gene 88 (MyD88).  The LRRs form a "horseshoe" shaped structure which is the ligand binding domain.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 5 different isoforms.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD289

CD289 binds unmethylated CpG DNA motifs.

Function
CD289 plays a fundamental role in pathogen recognition and activation of innate immunity.  
The Toll transmembrane receptor plays a central role in the signaling pathways.  TLRs are highly conserved from Drosophilia to humans and share structural and functional similarities.  They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity.  CD289 plays a fundamental role in pathogen recognition and activation of innate immunity.  Studies in mice and human indicate that CD289 mediates cellular response and acts as a receptor for unmethylated CpG dinucleotides in bacterial DNA present in endosomes during innate immune reponse to bacteria and viral infection.  Activation of  CD289 triggers MyD88 dependent signaling and induces high level production of IFN-1, particularly IFNα by plasmacytoid and bone marrow derived dendritic cells, mediates dendritic cell maturation and triggers a Th1 skewed adaptive immune response.  CD289 triggers MyD88 and TRAF6, leading to NF-κB activation, cytokine secretion and the inflammatory response.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD289 IN INTACT ANIMAL

CD289 deficient mice do not produce IFNα in response to challenge with herpesvirus and have impaired dendritic cell maturation.  Control of viral replication was the same in CD289 deficient and wild-type mice challenged with HSV-1, which suggests CD289 is not essential for defence abainst HSV-1.

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD289: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD289: No information.

ADDITIONAL INSIGHTS

For further information see Ahmad-Nejad, P. et al (2002) Eur. J. Immunol. 32: 1958-1968.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene54106Q9NR96
Antibodies

Revised June 25, 2008


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