The BTK protein is a 77 kDa protein of 659 amino acids. Translation of the BTK transcript starts at the ATG site that is located in exon 2 and ends in exon 19.
The BTK protein is composed of an N-terminal Pleckstrin homology (PH) domain followed three protein interacting domains: Tec homology (TH) region, Src homology 3 (SH3) domain and SH2 domain. A tyrosine-kinase catalytic domain is located at the C-terminal end. Two tyrosine phosphorylation sites are located at the positions Y223 and Y551, which are located in the SH3 and kinase domain, respectively. Both phosphorylation sites play a pivotal role in the activation of BTK. Y551 is transphosphorylated by Syk (or Lyn) kinases which promotes the catalytic activity of BTK, with subsequent autophosphorylation at position Y223.