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 domain (Broad-Complex, Tramtrack and Bric a brac) is also known as the POZ domain (POxvirus and Zinc finger). It is a homodimerization domain occurring at the N terminus of proteins containing multiple copies of either zinc fingers of the C2H2 type or Kelch repeats [ (PUBMED:7938017) (PUBMED:7958847) ]. Many BTB proteins are transcriptional regulators that are thought to act through the control of chromatin structure.

  The structure of the BTB domain of the promyelocytic leukemia zinc finger (PLZF) protein has been determined by X-ray crystallography and reveals a tightly intertwined dimer with an extensive hydrophobic interface [ (PUBMED:9770450) ]. A surface-exposed groove lined with conserved amino acids is formed at the dimer interface, suggesting a peptide-binding site.

• GO function: protein binding (GO:0005515)

There are 113741 BTB domains in 107385 proteins in SMART's nrdb database.

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

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

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

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)

% 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	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
3lbz	Crystal Structure of the BCL6 BTB domain complexed with the small molecule inhibitor 79-6
3lnm	F233W mutant of the Kv2.1 paddle-Kv1.2 chimera channel
3lut	A Structural Model for the Full-length Shaker Potassium Channel Kv1.2
3m4t	Crystal structure of the BTB domain from Kaiso/ZBTB33, form I
3m52	Crystal structure of the BTB domain from the Miz-1/ZBTB17 transcription regulator
3m5b	Crystal structure of the BTB domain from FAZF/ZBTB32
3m8v	Crystal structure of the BTB domain from Kaiso/ZBTB33, form II
3ohu	Crystal structure of the human Bach2 POZ domain, form I
3ohv	Crystal structure of the human Bach2 POZ domain, form II
4ap2	Crystal structure of the human KLHL11-Cul3 complex at 2.8A resolution
4apf	Crystal structure of the human KLHL11-Cul3 complex at 3.1A resolution
4bgc	T1 domain of the renal potassium channel Kv1.3
4cp3	The structure of BCL6 BTB (POZ) domain in complex with the ansamycin antibiotic rifabutin.
4crh	Crystal structure of the BTB-T1 domain of human SHKBP1
4cxi	4CXI
4cxj	4CXJ
4cxt	4CXT
4eoz	Crystal structure of the SPOP BTB domain complexed with the Cul3 N-terminal domain
4hxi	Crystal structure of KLHL3/Cul3 complex
4j8z	Crystal Structure of the Human SPOP BTB Domain
4jta	Crystal structure of Kv1.2-2.1 paddle chimera channel in complex with Charybdotoxin
4jtc	Crystal structure of Kv1.2-2.1 paddle chimera channel in complex with Charybdotoxin in Cs+
4jtd	Crystal structure of Kv1.2-2.1 paddle chimera channel in complex with Lys27Met mutant of Charybdotoxin
4u2m	4U2M
4u2n	4U2N
4u77	4U77
4uij	4UIJ
4uyi	4UYI
4yy8	4YY8
4zgc	4ZGC
5a15	5A15
5a6r	5A6R
5bxb	5BXB
5bxd	5BXD
5bxh	5BXH
5dad	5DAD
5daf	5DAF
5eup	5EUP
5fta	5FTA

Links (links to other resources describing this domain)

• PFAM: BTB
• INTERPRO: IPR000210