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59  structures 285  species 3  interactions 3855  sequences 108  architectures

Family: BTB_2 (PF02214)

Summary: BTB/POZ domain

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Potassium channel tetramerisation domain". More...

Potassium channel tetramerisation domain Edit Wikipedia article

K+ channel tetramerisation domain
PDB 1t1d EBI.jpg
Identifiers
Symbol K_tetra
Pfam PF02214
InterPro IPR003131
SCOP 1t1d
SUPERFAMILY 1t1d
OPM superfamily 8
OPM protein 2a79

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[edit]

Potassium channels are the most diverse group of the ion channel family.[2][3] They are important in shaping the action potential, and in neuronal excitability and plasticity.[4] The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups:[5] 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.[6] 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.[7] In prokaryotic cells, they play a role in the maintenance of ionic homeostasis.[8]

Alpha subunits of the channels[edit]

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).[8][9] 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.[10] 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.[11] When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.

Tetramerization domain[edit]

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.[12] This domain is found in a subset of a larger group of proteins that contain the BTB/POZ domain.

Human proteins containing this domain[edit]

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;

References[edit]

  1. ^ Bixby KA, Nanao MH, Shen NV et al. (January 1999). "Zn2+-binding and molecular determinants of tetramerization in voltage-gated K+ channels". Nature Structural & Molecular Biology 6 (1): 38–43. doi:10.1038/4911. PMID 9886290. 
  2. ^ Perney TM, Kaczmarek LK (1991). "The molecular biology of K+ channels". Curr. Opin. Cell Biol. 3 (4): 663–670. doi:10.1016/0955-0674(91)90039-2. PMID 1772658. 
  3. ^ 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): 163–167. doi:10.1016/0014-5793(91)81026-5. PMID 1879548. 
  4. ^ Jan LY, Jan YN, Tempel BL (1988). "Cloning of a probable potassium channel gene from mouse brain". Nature 332 (6167): 837–839. doi:10.1038/332837a0. PMID 2451788. 
  5. ^ 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): 3235–3244. PMC 401447. PMID 2555158. 
  6. ^ 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): 137–142. doi:10.1038/331137a0. PMID 2448635. 
  7. ^ 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): 8650–8657. PMID 1373731. 
  8. ^ a b Miller C (2000). "An overview of the potassium channel family". Genome Biol. 1 (4): –. doi:10.1186/gb-2000-1-4-reviews0004. PMC 138870. PMID 11178249. 
  9. ^ Ashcroft FM (2000). Voltage-gated K+ channels. pp. 97–123. 
  10. ^ Sansom MS (2000). "Potassium channels: watching a voltage-sensor tilt and twist". Curr. Biol. 10 (5): R206–9. doi:10.1016/S0960-9822(00)00354-7. PMID 10712896. 
  11. ^ 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): 24371–24379. doi:10.1074/jbc.272.39.24371. PMID 9305895. 
  12. ^ 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". Nature Structural & Molecular Biology 6 (1): 38–43. doi:10.1038/4911. PMID 9886290. 

Further reading[edit]

  • 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 & Molecular Biology 6 (1): 38–43. doi:10.1038/4911. PMID 9886290. 

This article incorporates text from the public domain Pfam and InterPro IPR003131

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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 [1]. In KCTD1 (Q719H9) this domain functions as a transcriptional repressor [2]. It also mediates homomultimerisation of KCTD1 and interaction of KCTD1 with the transcription factor AP-2-alpha [2-3].

Literature references

  1. 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

  2. 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

  3. 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].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan POZ (CL0033), which has the following description:

The POZ domain is found in a variety of transcription factors. POZ domains are also found in the tetramerisation domain of voltage gated K+ channels. In general these domains mediate homo-oligomerisation.

The clan contains the following 5 members:

BACK BTB BTB_2 DUF3342 Skp1_POZ

Alignments

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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.

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(46)
Full
(3855)
Representative proteomes NCBI
(3406)
Meta
(33)
RP15
(702)
RP35
(944)
RP55
(1575)
RP75
(2405)
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  Seed
(46)
Full
(3855)
Representative proteomes NCBI
(3406)
Meta
(33)
RP15
(702)
RP35
(944)
RP55
(1575)
RP75
(2405)
Alignment:
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  Seed
(46)
Full
(3855)
Representative proteomes NCBI
(3406)
Meta
(33)
RP15
(702)
RP35
(944)
RP55
(1575)
RP75
(2405)
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External links

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Pfam alignments:

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Trees

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Curation and family details

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Curation View help on the curation process

Seed source: Pfam-B_27 (Release 5.2)
Previous IDs: K_tetra;
Type: Domain
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.8 20.8
Trusted cut-off 20.8 20.8
Noise cut-off 20.7 20.7
Model length: 94
Family (HMM) version: 17
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Species distribution

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Interactions

There are 3 interactions for this family. More...

Aldo_ket_red BTB_2 Shal-type

Structures

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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