BTB (also known as POZ) was first identified as a conserved motif presented in the Drosophila melanogaster Bric-a-Brac, Tramtrack, Broad complex transcription regulators (1). BTB, Cul3 and RBX1 form a Cul3-based ligase (BCR), which targets substrates for ubiquitin-dependent degradation by the 26S proteasome. As a substrate recognition subunit of Cul3-based ligase, the member of BTB family can bridge the Cul3 to the substrate in a single polypeptide (2,3). Recently, it was observed that a 3-box is responsible for the Cul3-interacting in a variety of BTB proteins including almost all of BTB-Kelch and MATH-BTB proteins (4). Here we defined the BTB_3-box family as the proteins contain both BTB domain and 3-box domain. BTB-containing proteins are highly conserved and participate in diverse biological processes, including transcriptional regulation, ion channel assembly and gating, cytoskeleton dynamics, and targeting proteins for ubiquitination (1).

1. Stogios, P.J., Downs, G.S., Jauhal, J.J., Nandra, S.K. and Prive, G.G. (2005). Sequence and structural analysis of BTB domain proteins. Genome Biol., 6, R82. PMID: 16207353

2. Xu, L., Wei, Y., Reboul, J., Vaglio, P., Shin, T.H., Vidal, M., Elledge, S.J. and Harper, J.W. (2003). BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3. Nature, 425, 316-321. PMID: 13679922

3. Pintard, L., Willems, A. and Peter, M. (2004). Cullin-based ubiquitin ligases: Cul3-BTB complexes join the family. EMBO J., 23, 1681-1687. PMID: 15071497

4. Zhuang, M., Calabrese, M.F., Liu, J., Waddell, M.B., Nourse, A., Hammel, M., Miller, D.J., Walden, H., Duda, D.M., Seyedin, S.N., Hoggard, T., Harper, J. W., White, K. P. and Schulman, B. A.. (2009). Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases. Mol. Cell, 36(1): 39-50. PMID: 19818708