Bruton tyrosine kinase; agammaglobulinemia tyrosine kinase; ATK; B-cell progenitor tyrosine kinase (BPK, BTK, AGMX1)

Function

• plays a crucial role in B-cell ontogeny
• transiently phosphorylates GTF2I on Tyr in response to B-cell receptor cross-linking
• required for formation of functional ARID3A DNA-binding complexes
• binds GTF2I through the PH domain
• interacts with SH3BP5 via the SH3 domain
• interacts with IBTK via its PH domain
• interacts with GTF2I & ARID3A
• inhibited by IBTK
• activated by phosphorylation
• autophosphorylated on Tyr-223 & Tyr-551
• phosphorylation of Tyr-223 may create a docking site for a SH2 containing protein

Cofactor: binds 1 Zn+2 per subunit

* see figure

Structure

• belongs to the protein kinase superfamily, Tyr protein kinase family, TEC subfamily
• contains 1 Btk-type Zn+2 finger
• contains 1 PH domain
• contains 1 protein kinase domain
• contains 1 SH2 domain
• contains 1 SH3 domain

Compartment

• cytoplasm, membrane, nucleus

Pathology

• defects in BTK are the cause of
  • Bruton type agammaglobulinemia
  • Fleisher syndrome

Pharmacology

• ibrutinib a small-molecule inhibitor of BTK is used for the treatment of CLL

Laboratory

• Bruton tyrosine kinase in B cells+monocytes

More general terms

• tyrosine kinase (protein tyrosine kinase, PTK)

Additional terms

• ibrutinib (Imbruvica)

Database

• UniProt: http://www.uniprot.org/uniprot/Q06187.html
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:695
• OMIM: https://mirror.omim.org/entry/300300
• OMIM: https://mirror.omim.org/entry/307200