Summary: BTB/POZ domain
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Potassium channel tetramerisation domain Edit Wikipedia article
|K+ channel tetramerisation domain|
K+ channel tetramerisation domain is the N-terminal, cytoplasmic tetramerisation domain (T1) of voltage-gated K+ channels. It defines molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. It is distantly related to the BTB/POZ domain Pfam PF00651.
 Potassium channels
Potassium channels are the most diverse group of the ion channel family. They are important in shaping the action potential, and in neuronal excitability and plasticity. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.
These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers. In eukaryotic cells, K+ channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis.
 Alpha subunits of the channels
All K+ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+ channels; and three types of calcium (Ca)-activated K+ channels (BK, IK and SK). The 2TM domain family comprises inward-rectifying K+ channels. In addition, there are K+ channel alpha-subunits that possess two P-domains. These are usually highly regulated K+ selective leak channels.
The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.
 Tetramerization domain
The N-terminal, cytoplasmic tetramerization domain (T1) of voltage-gated potassium channels encodes molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. This domain is found in a subset of a larger group of proteins that contain the BTB/POZ domain.
 Human proteins containing this domain
BTBD10; KCNA1; KCNA10; KCNA2; KCNA3; KCNA4; KCNA5; KCNA6; KCNA7; KCNB1; KCNB2; KCNC1; KCNC2; KCNC3; KCNC4; KCND1; KCND2; KCND3; KCNF1; KCNG1; KCNG2; KCNG3; KCNG4; KCNRG; KCNS1; KCNS2; KCNS3; KCNV1; KCNV2; KCTD1; KCTD10; KCTD11; KCTD12; KCTD13; KCTD14; KCTD15; KCTD16; KCTD17; KCTD18; KCTD19; KCTD2; KCTD20; KCTD21; KCTD3; KCTD4; KCTD5; KCTD6; KCTD7; KCTD8; KCTD9; SHKBP1; TNFAIP1;
- Bixby KA, Nanao MH, Shen NV et al. (January 1999). "Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels". Nat. Struct. Biol. 6 (1): 38â43. doi:10.1038/4911. PMID 9886290.
- Perney TM, Kaczmarek LK (1991). "The molecular biology of K+ channels". Curr. Opin. Cell Biol. 3 (4): 663â670. doi:10.1016/0955-0674(91)90039-2. PMID 1772658.
- Williams JB, Luneau C, Smith JS, Wiedmann R (1991). "Shaw-like rat brain potassium channel cDNA's with divergent 3' ends". FEBS Lett. 288 (1): 163â167. doi:10.1016/0014-5793(91)81026-5. PMID 1879548.
- Jan LY, Jan YN, Tempel BL (1988). "Cloning of a probable potassium channel gene from mouse brain". Nature 332 (6167): 837â839. doi:10.1038/332837a0. PMID 2451788.
- Stuhmer W, Ruppersberg JP, Schroter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O (1989). "Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain". EMBO J. 8 (11): 3235â3244. PMC 401447. PMID 2555158. //www.ncbi.nlm.nih.gov/pmc/articles/PMC401447/.
- Jan LY, Jan YN, Schwarz TL, Tempel BL, Papazian DM (1988). "Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila". Nature 331 (6152): 137â142. doi:10.1038/331137a0. PMID 2448635.
- Mattei MG, Lesage F, Lazdunski M, Romey G, Barhanin J, Attali B, Honore E, Ricard P, Schmid-Alliana A (1992). "Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes". J. Biol. Chem. 267 (12): 8650â8657. PMID 1373731.
- Miller C (2000). "An overview of the potassium channel family". Genome Biol. 1 (4): â. doi:10.1186/gb-2000-1-4-reviews0004. PMC 138870. PMID 11178249. //www.ncbi.nlm.nih.gov/pmc/articles/PMC138870/.
- Ashcroft FM (2000). Voltage-gated K+ channels. pp. 97â123.
- Sansom MS (2000). "Potassium channels: watching a voltage-sensor tilt and twist". Curr. Biol. 10 (5): R206â9. doi:10.1016/S0960-9822(00)00354-7. PMID 10712896.
- Duprat F, Lazdunski M, Heurteaux C, Salinas M, Hugnot JP (1997). "New modulatory alpha subunits for mammalian Shab K+ channels". J. Biol. Chem. 272 (39): 24371â24379. doi:10.1074/jbc.272.39.24371. PMID 9305895.
- Kreusch A, Choe S, Bixby KA, Nanao MH, Shen NV, Bellamy H, Pfaffinger PJ (1999). "Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels". Nat. Struct. Biol. 6 (1): 38â43. doi:10.1038/4911. PMID 9886290.
 Further reading
- Bixby, KA; Nanao, MH; Shen, NV; Kreusch, A; Bellamy, H; Pfaffinger, PJ; Choe, S (1999). "Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels". Nature structural biology 6 (1): 38â43. doi:10.1038/4911. PMID 9886290.
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BTB/POZ domain Provide feedback
In voltage-gated K+ channels this domain is responsible for subfamily-specific assembly of alpha-subunits into functional tetrameric channels . In KCTD1 (Q719H9) this domain functions as a transcriptional repressor . It also mediates homomultimerisation of KCTD1 and interaction of KCTD1 with the transcription factor AP-2-alpha [2-3].
Bixby KA, Nanao MH, Shen NV, Kreusch A, Bellamy H, Pfaffinger PJ, Choe S; , Nat Struct Biol 1999;6:38-43.: Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels. PUBMED:9886290 EPMC:9886290
Ding XF, Luo C, Ren KQ, Zhang J, Zhou JL, Hu X, Liu RS, Wang Y, Gao X, Zhang J;, DNA Cell Biol. 2008;27:257-265.: Characterization and expression of a human KCTD1 gene containing the BTB domain, which mediates transcriptional repression and homomeric interactions. PUBMED:18358072 EPMC:18358072
Ding X, Luo C, Zhou J, Zhong Y, Hu X, Zhou F, Ren K, Gan L, He A, Zhu J, Gao X, Zhang J;, J Cell Biochem. 2009;106:285-295.: The interaction of KCTD1 with transcription factor AP-2alpha inhibits its transactivation. PUBMED:19115315 EPMC:19115315
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR003131
This domain can be found at the N terminus of voltage-gated potassium channel proteins, where represents a cytoplasmic tetramerisation domain (T1) involved in assembly of alpha-subunits into functional tetrameric channels [PUBMED:9886290]. This domain can also be found in proteins that are not potassium channels, like KCTD1 (potassium channel tetramerisation domain-containing protein 1). KCTD1 is though to be a nuclear protein that functions as a transcriptional repressor. In KCTD1, the T1-type BTB domain mediates homomeric protein-protein interactions [PUBMED:18358072, PUBMED:19115315].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||protein homooligomerization (GO:0051260)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
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a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
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- alignment generated by searching the NCBI sequence database using the family HMM
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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
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MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
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This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
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Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_27 (Release 5.2)|
|Author:||Bateman A, Eberhardt R|
|Number in seed:||46|
|Number in full:||3855|
|Average length of the domain:||92.00 aa|
|Average identity of full alignment:||29 %|
|Average coverage of the sequence by the domain:||21.51 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||17|
|Download:||download the raw HMM for this family|
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
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There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the BTB_2 domain has been found. There are 59 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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