Chickens express TLR21 which is absent in human; chTLR21 has orthologs in fish and frog genomes and shows similarity with murine TLR13. Cloning and expression analysis revealed that the TLR21 gene encodes a protein of 972 amino acids residues. The protein was predicted to contain an extracellular domain containing 27 leucine rich regions (LRR), a single trans membrane region and cytoplasmic TIR domain, thus resembling the protein architecture of TLR family members.
It has been reported that despite the low similarity in amino acid sequence, chTLR21 senses DNA and acts as a functional homologue of mammalian TLR9.(Keestra et al. 2010). Confocal microscopy located chTLR21 in the endoplasmic reticulum. Besides, inhibition of the chTLR21-mediated response by bafilomycin A (Brownlie R et al 2009) or chloroquine(Keestra AM et al 2010) suggested that endosomal maturation is required for the receptor activation, as is the case for mammalian TLR9.
A direct structural orthologue to mammalian TLR9 is absent in the chicken genome.