Conserved Site

Zinc finger, Btk motif (IPR001562)

Short name: Znf_Btk_motif


The Btk-type zinc finger or Btk motif (BM) 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 (Btk), an enzyme which is essential for B cell maturation in humans and mice [PMID: 8070576, PMID: 15661031]. Btk is a member of the Tec family of protein tyrosine kinases (PTK). These kinases contain a conserved Tec homology (TH) domain between the N-terminal pleckstrin homology (PH) domain (IPR001849) and the Src homology 3 (SH3) domain (IPR001452). 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 (PRR). The Btk motif contains a conserved His and three Cys residues that form a zinc finger (although these differ from known zinc finger topologies), while PRRs are commonly involved in protein-protein interactions, including interactions with G proteins [PMID: 9280283, PMID: 9796816]. The TH domain may be of functional importance in various signalling pathways in different species [PMID: 8070576]. 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 (note that although a Btk motif always occurs C-terminal to a PH domain, not all PH domains are followed by a Btk motif).

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 [PMID: 8070576]. The zinc-binding residues are a histidine and three cysteines, which are fully conserved in the Btk motif [PMID: 9218782].

Proteins known to contain a Btk-type zinc finger include:

  • Mammalian Bruton's tyrosine kinase (Btk), a protein tyrosine kinase involved in modulation of diverse cellular processes. Mutations affecting Btk are the cause of X-linked agammaglobulinemia (XLA) 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 (RasGAP), which regulate the activation of inactive GDP-bound Ras by converting GDP to GTP.

GO terms

Biological Process

GO:0035556 intracellular signal transduction

Molecular Function

No terms assigned in this category.

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE profiles