Summary: Calcium-activated potassium channel, beta subunit

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Wikipedia: Calcium-activated potassium channel beta subunit
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This is the Wikipedia entry entitled "Calcium-activated potassium channel beta subunit". More...

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Calcium-activated potassium channel beta subunit Edit Wikipedia article

CaKB

solution structure of the cytoplasmic n-terminus of the bk beta-subunit kcnmb2

Identifiers

Symbol

CaKB

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

In molecular biology, the calcium-activated potassium channel beta subunit is a family of proteins comprising the beta subunits of calcium-actived potassium channels.

The functional diversity of potassium channels can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. The beta subunit (which is thought to possess 2 transmembrane domains) increases the calcium sensitivity of the BK channel.^[1] It does this by enhancing the time spent by the channel in burst-like open states. However, it has little effect on the durations of closed intervals between bursts, or on the numbers of open and closed states entered during gating.^[2]

[edit] References

^ McManus OB, Helms LM, Pallanck L, Ganetzky B, Swanson R, Leonard RJ (March 1995). "Functional role of the beta subunit of high conductance calcium-activated potassium channels". Neuron 14 (3): 645–50. doi:10.1016/0896-6273(95)90321-6. PMID 7695911.
^ Nimigean CM, Magleby KL (March 1999). "The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states". J. Gen. Physiol. 113 (3): 425–40. PMC 2222905. PMID 10051518. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2222905.

This article incorporates text from the public domain Pfam and InterPro IPR003930

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

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No Pfam abstract.

Literature references

Wallner M, Meera P, Toro L; , Proc Natl Acad Sci U S A 1999;96:4137-4142.: Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: a transmembrane beta-subunit homolog. PUBMED:10097176 EPMC:10097176

External database links

PANDIT:	PF03185
Pseudofam:	PF03185
SCOP:	1jo6
SYSTERS:	CaKB
Transporter classification:	8.A.14

This tab holds annotation information from the InterPro database.

InterPro entry IPR003930

Potassium channels are the most diverse group of the ion channel family [PUBMED:1772658, PUBMED:1879548]. They are important in shaping the action potential, and in neuronal excitability and plasticity [PUBMED:2451788]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [PUBMED:2555158]: 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 [PUBMED:2448635]. 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 [PUBMED:1373731]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [PUBMED:11178249].

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) [PUBMED:11178249]. 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.

Ca2+-activated K+ channels are a diverse group of channels that are activated by an increase in intracellular Ca2+ concentration. They are found in the majority of nerve cells, where they modulate cell excitability and action potential. Three types of Ca2+-activated K+ channel have been characterised, termed small-conductance (SK), intermediate conductance (IK) and large conductance (BK) respectively [PUBMED:9687354].

BK channels (also referred to as maxi-K channels) are widely expressed in the body, being found in glandular tissue, smooth and skeletal muscle, as well as in neural tissues. They have been demonstrated to regulate arteriolar and airway diameter, and also neurotransmitter release. Each channel complex is thought to be composed of 2 types of subunit: the pore- forming (alpha) subunits and smaller accessory (beta) subunits.

The beta subunit (which is thought to possess 2 TM domains) increases the Ca2+ sensitivity of the BK channel [PUBMED:7695911]. It does this by enhancing the time spent by the channel in burst-like open states. However, it has little effect on the durations of closed intervals between bursts, or on the numbers of open and closed states entered during gating [PUBMED:10051518].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Cellular component	membrane (GO:0016020)
Molecular function	calcium-activated potassium channel activity (GO:0015269)
Biological process	potassium ion transport (GO:0006813)

Domain organisation

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

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics 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.

	Seed (10)	Full (225)	Representative proteomes				NCBI (207)	Meta (0)
	Seed (10)	Full (225)	RP15 (26)	RP35 (31)	RP55 (56)	RP75 (119)	NCBI (207)	Meta (0)
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HTML	View	View	View	View	View	View
PP/heatmap	₁	View	View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (10)	Full (225)	Representative proteomes				NCBI (207)	Meta (0)
	Seed (10)	Full (225)	RP15 (26)	RP35 (31)	RP55 (56)	RP75 (119)	NCBI (207)	Meta (0)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

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.

	Seed (10)	Full (225)	Representative proteomes				NCBI (207)	Meta (0)
	Seed (10)	Full (225)	RP15 (26)	RP35 (31)	RP55 (56)	RP75 (119)	NCBI (207)	Meta (0)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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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Trees

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.

Note: You can also download the data file for the tree.

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.

Curation

Seed source:

Pfam-B_2176 (release 6.5)

Previous IDs:

none

Type:

Family

Author:

Mifsud W

Number in seed:

10

Number in full:

225

Average length of the domain:

174.90 aa

Average identity of full alignment:

38 %

Average coverage of the sequence by the domain:

79.42 %

HMM information

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	25.0	25.0
Trusted cut-off	25.1	26.3
Noise cut-off	23.7	24.4

Model length:

201

Family (HMM) version:

10

Download:

download the raw HMM for this family

Species distribution

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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.

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family
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species

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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".

Sub-species

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.

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Species trees

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.

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Interactive tree

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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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 CaKB domain has been found. There are 1 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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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: CaKB (PF03185)

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