Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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BTB Broad-Complex, Tramtrack and Bric a brac

SMART accession number:	SM00225
Description:	Domain in Broad-Complex, Tramtrack and Bric a brac. Also known as POZ (poxvirus and zinc finger) domain. Known to be a protein-protein interaction motif found at the N-termini of several C2H2-type transcription factors as well as Shaw-type potassium channels. Known structure reveals a tightly intertwined dimer formed via interactions between N-terminal strand and helix structures. However in a subset of BTB/POZ domains, these two secondary structures appear to be missing. Be aware SMART predicts BTB/POZ domains without the beta1- and alpha1-secondary structures.
Interpro abstract (IPR000210):	The BTB (for BR-C, ttk and bab) [(PUBMED:7938017)] or POZ (for Pox virus and Zinc finger) [(PUBMED:7958847)] domain is present near the N terminus of a fraction of zinc finger (IPR007087) proteins and in proteins that contain the IPR006652 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerisation and in some instances heteromeric dimerisation [(PUBMED:7958847)]. The structure of the dimerised PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule [(PUBMED:9770450)]. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT [(PUBMED:9019154), (PUBMED:9824158), (PUBMED:9765306)]. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.
GO function:	protein binding (GO:0005515)
Family alignment:	View or CHROMA formatCLUSTALW formatMSF formatFASTA formatPIR format

There are 10473 BTB domains in 9905 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a BTB domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with BTB domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Aravind L, Koonin EV
  • Fold prediction and evolutionary analysis of the POZ domain: structural and evolutionary relationship with the potassium channel tetramerization domain.
  • J Mol Biol. 1999; 285: 1353-61
  • Display abstract

  • Using iterative database searches, a statistically significant sequence similarity was detected between the POZ (poxvirus and zinc finger) domains found in a variety of proteins involved in animal transcription regulation, cytoskeleton organization, and development, and the tetramerization domain of animal potassium channels. Using the crystal structure of the Aplysia Shaker channel tetramerization domain as a template, the common structure of the POZ domain class was predicted. Examination of the structure resulted in the identification of several structural features and specific amino acid residues that may be involved in conserved protein-protein interactions mediated by the POZ domains as well as those that may contribute to the specificity of these interactions. Phylogenetic analysis of the POZ domains suggests that the common ancestor of the crown group eukaryotes already possessed this domain; POZ domains have undergone independent expansion in plants and in different animal lineages.

  • Kreusch A, Pfaffinger PJ, Stevens CF, Choe S
  • Crystal structure of the tetramerization domain of the Shaker potassium channel.
  • Nature. 1998; 392: 945-8
  • Display abstract

  • Voltage-dependent, ion-selective channels such as Na+, Ca2+ and K+ channel proteins function as tetrameric assemblies of identical or similar subunits. The clustering of four subunits is thought to create an aqueous pore centred at the four-fold symmetry axis. The highly conserved, amino-terminal cytoplasmic domain (approximately 130 amino acids) immediately preceding the first putative transmembrane helix S1 is designated T1. It is known to confer specificity for tetramer formation, so the heteromeric assembly of K+-channel subunits is an important mechanism for the observed channel diversity. We have determined the crystal structure of the T1 domain of a Shaker potassium channel at 1.55 A resolution. The structure reveals that four identical subunits are arranged in a four-fold symmetry surrounding a centrally located pore about 20 A in length. Subfamily-specific assembly is provided primarily by polar interactions encoded in a conserved set of amino acids at its tetramerization interface. Most highly conserved amino acids in the T1 domain of all known potassium channels are found in the core of the protein, indicating a common structural framework for the tetramer assembly.

  • Bardwell VJ, Treisman R
  • The POZ domain: a conserved protein-protein interaction motif.
  • Genes Dev. 1994; 8: 1664-77
  • Display abstract

  • We describe a novel zinc finger protein, ZID (zinc finger protein with interaction domain). At its amino terminus ZID contains a 120-amino-acid conserved motif present in a large family of proteins that includes both the otherwise unrelated zinc finger proteins, such as Ttk, GAGA, and ZF5, and a group of poxvirus proteins: We therefore refer to this domain as the POZ (poxvirus and zinc finger) domain. The POZ domains of ZID, Ttk, and GAGA act to inhibit the interaction of their associated finger regions with DNA. This inhibitory effect is not dependent on interactions with other proteins and does not appear dependent on specific interactions between the POZ domain and the finger region. The POZ domain acts as a specific protein-protein interaction domain: The POZ domains of ZID and Ttk can interact with themselves but not with each other, POZ domains from ZF5, or the viral protein SalF17R. However, the POZ domain of GAGA can interact efficiently with the POZ domain of Ttk. In transfection experiments, the ZID POZ domain inhibits DNA binding in NIH-3T3 cells and appears to localize the protein to discrete regions of the nucleus. We discuss the implications of multimerization for the function of POZ domain proteins.

  • Koonin EV, Senkevich TG, Chernos VI
  • A family of DNA virus genes that consists of fused portions of unrelated cellular genes.
  • Trends Biochem Sci. 1992; 17: 213-4
• Disease (disease genes where sequence variants are found in this domain)

• SwissProt sequences and OMIM curated human diseases associated with missense mutations within the BTB domain.

  Protein	Disease
  Gigaxonin (Q9H2C0) (SMART)	OMIM:256850: Giant axonal neuropathy-1 OMIM:605379: Giant axonal neuropathy-1 OMIM:256850:

• Metabolism (metabolic pathways involving proteins which contain this domain)

• Click the image to view the interactive version of the map in iPath

  % proteins involved KEGG pathway ID Description 53.06 map04120 Ubiquitin mediated proteolysis 16.33 map05221 Acute myeloid leukemia 12.24 map04742 Taste transduction 4.08 map00561 Glycerolipid metabolism 2.04 map00564 Glycerophospholipid metabolism 2.04 map00626 Naphthalene and anthracene degradation 2.04 map00903 Limonene and pinene degradation 2.04 map00361 gamma-Hexachlorocyclohexane degradation 2.04 map00600 Sphingolipid metabolism 2.04 map03320 PPAR signaling pathway 2.04 map04320 Dorso-ventral axis formation This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with BTB domain which could be assigned to a KEGG orthologous group, and not all proteins containing BTB domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Structure (3D structures containing this domain)

• 3D Structures of BTB domains in PDB

  PDB code	Main view	Title
  1a68		Crystal structure of the tetramerization domain of the shaker potassium channel
  1buo		Btb domain from plzf
  1cs3		Structure of btb/poz transcription repression domain from promelocytic leukemia zinc finger oncoprotein
  1dsx		Kv1.2 t1 domain, residues 33-119, t46v mutant
  1eod		Crystal structure of the n136d mutant of a shaker t1 domain
  1eoe		Crystal structure of the v135r mutant of a shaker t1 domain
  1eof		Crystal structure of the n136a mutant of a shaker t1 domain
  1exb		Structure of the cytoplasmic beta subunit-t1 assembly of voltage-dependent k channels
  1nn7		Crystal structure of the tetramerization domain of the shal voltage-gated potassium channel
  1qdv		N-terminal domain, voltage-gated potassium channel kv1.2 residues 33-131
  1qdw		N-terminal domain, voltage-gated potassium channel kv1.2 residues 33-119
  1r28		Crystal structure of the b-cell lymphoma 6 (bcl6) btb domain to 2.2 angstrom
  1r29		Crystal structure of the b-cell lymphoma 6 (bcl6) btb domain to 1.3 angstrom
  1r2b		Crystal structure of the bcl6 btb domain complexed with a smrt co-repressor peptide
  1s1g		Crystal structure of kv4.3 t1 domain
  1t1d		Crystal structure of the tetramerization domain of the shaker potassium channel
  2a79		Mammalian shaker kv1.2 potassium channel- beta subunit complex
  2i2r		Crystal structure of the kchip1/kv4.3 t1 complex
  2if5		Structure of the poz domain of human lrf, a master regulator of oncogenesis
  2ihc		Crystal structure of the bric-a-brac (btb) domain of human bach1
  2nn2		Crystal structure of the btb domain from the lrf/zbtb7 transcriptional regulator
  2nz0		Crystal structure of potassium channel kv4.3 in complex with its regulatory subunit kchip1 (casp target)
  2ppi		Structure of the btb (tramtrack and bric a brac) domain of human gigaxonin
  2q81		Crystal structure of the miz-1 btb/poz domain
  2r9r		Shaker family voltage dependent potassium channel (kv1.2- kv2.1 paddle chimera channel) in association with beta subunit
  2vkp		Crystal structure of btb domain from btbd6
  2vpk		Crystal structure of the btb domain of human myoneurin
  2yy9		Crystal structure of btb domain from mouse hkr3
  2z8h		Structure of mouse bach1 btb domain
  3b84		Crystal structure of the human btb domain of the krueppel related zinc finger protein 3 (hkr3)
  3bim		Crystal structure of the bcl6 btb domain dimer in complex with the bcor bbd corepressor peptide
  3drx		X-ray crystal structure of human kctd5 protein crystallized in high-salt buffer
  3dry		X-ray crystal structure of human kctd5 protein crystallized in low-salt buffer
  3drz		X-ray crystal structure of the n-terminal btb domain of human kctd5 protein
  3e4u		Crystal structure of the wild-type human bcl6 btb/poz domain
  3fkc		Crystal structure of human zinc finger and btb domain containing 33
  3ga1		Crystal structure of the human nac1 poz domain
  3hqi		Structures of spop-substrate complexes: insights into molecular architectures of btb-cul3 ubiquitin ligases: spopmathx/btb/3-box-pucsbc1
  3htm		Structures of spop-substrate complexes: insights into molecular architectures of btb-cul3 ubiquitin ligases: spopbtb/3-box
  3hu6		Structures of spop-substrate complexes: insights into molecular architectures of btb-cul3 ubiquitin ligases: spopmathx/btb/3-box-pucsbc1
  3hve		Structures of spop-substrate complexes: insights into molecular architectures of btb-cul3 ubiquitin ligases: gigaxoninbtb/3-box
  3i3n		Crystal structure of the btb-back domains of human klhl11
  3kvt		Tetramerization domain from akv3.1 (shaw-subfamily) voltage- gated potassium channel

• Links (links to other resources describing this domain)

• PFAM	BTB
  INTERPRO	IPR000210

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