Sequence and structural analysis of BTB domain proteins

Genome Biol. 2005;6(10):R82. doi: 10.1186/gb-2005-6-10-r82. Epub 2005 Sep 15.


Background: The BTB domain (also known as the POZ domain) is a versatile protein-protein interaction motif that participates in a wide range of cellular functions, including transcriptional regulation, cytoskeleton dynamics, ion channel assembly and gating, and targeting proteins for ubiquitination. Several BTB domain structures have been experimentally determined, revealing a highly conserved core structure.

Results: We surveyed the protein architecture, genomic distribution and sequence conservation of BTB domain proteins in 17 fully sequenced eukaryotes. The BTB domain is typically found as a single copy in proteins that contain only one or two other types of domain, and this defines the BTB-zinc finger (BTB-ZF), BTB-BACK-kelch (BBK), voltage-gated potassium channel T1 (T1-Kv), MATH-BTB, BTB-NPH3 and BTB-BACK-PHR (BBP) families of proteins, among others. In contrast, the Skp1 and ElonginC proteins consist almost exclusively of the core BTB fold. There are numerous lineage-specific expansions of BTB proteins, as seen by the relatively large number of BTB-ZF and BBK proteins in vertebrates, MATH-BTB proteins in Caenorhabditis elegans, and BTB-NPH3 proteins in Arabidopsis thaliana. Using the structural homology between Skp1 and the PLZF BTB homodimer, we present a model of a BTB-Cul3 SCF-like E3 ubiquitin ligase complex that shows that the BTB dimer or the T1 tetramer is compatible in this complex.

Conclusion: Despite widely divergent sequences, the BTB fold is structurally well conserved. The fold has adapted to several different modes of self-association and interactions with non-BTB proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Genome / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Phylogeny
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA
  • Sequence Analysis, Protein*
  • Zinc Fingers / genetics


  • DNA-Binding Proteins