Btk-type zinc finger
In molecular biology, the Btk-type zinc finger or Btk motif is a conserved zinc-binding motif containing conserved cysteines and a histidine that is present in certain eukaryotic signalling proteins. The motif is named after Bruton's tyrosine kinase, an enzyme which is essential for B cell maturation in humans and mice. Btk is a member of the Tec family of protein tyrosine kinases. These kinases contain a conserved Tec homology domain between the N-terminal pleckstrin homology domain and the Src homology 3 domain. The N-terminal of the TH domain is highly conserved and known as the Btf motif, while the C-terminal region of the TH domain contains a proline-rich region. The Btk motif contains a conserved His and three Cys residues that form a zinc finger, while PRRs are commonly involved in protein-protein interactions, including interactions with G proteins. The TH domain may be of functional importance in various signalling pathways in different species. A complete TH domain, containing both the Btk and PRR regions, has not been found outside the Tec family; however, the Btk motif on its own does occur in other proteins, usually C-terminal to a PH domain.
The crystal structures of Btk show that the Btk-type zinc finger has a globular core, formed by a long loop which is held together by a zinc ion, and that the Btk motif is packed against the PH domain. The zinc-binding residues are a histidine and three cysteines, which are fully conserved in the Btk motif.
Proteins known to contain a Btk-type zinc finger include:
- Mammalian Bruton's tyrosine kinase, a protein tyrosine kinase involved in modulation of diverse cellular processes. Mutations affecting Btk are the cause of X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice.
- Mammalian Tec, Bmx, and Itk proteins, which are tyrosine protein kinases of the Tec subfamily.
- Drosophila tyrosine-protein kinase Btk29A, which is required for the development of proper ring canals and of male genitalia and required for adult survival.
- Mammalian Ras GTPase-activating proteins, which regulate the activation of inactive GDP-bound Ras by converting GDP to GTP.