Summary: Voltage gated chloride channel
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 "Chloride channel". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Chloride channel Edit Wikipedia article
|Voltage gated chloride channel|
Clc chloride channel ()
|SCOPe||1kpl / SUPFAM|
Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions. Several families of voltage-gated channels and ligand-gated channels (e.g., the CaCC families) have been characterized in humans.
Voltage-gated chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups.
- 1 General functions
- 2 CLC family
- 3 E-ClC family
- 4 CLIC family
- 5 CFTR
- 6 Other chloride channels and families
- 7 References
- 8 Further reading
- 9 External links
Voltage-gated chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct Clâˆ’ or other anions such as HCOâˆ’
3, Iâˆ’, SCNâˆ’, and NOâˆ’
3. The structure of these channels are not like other known channels. The chloride channel subunits contain between 1 and 12 transmembrane segments. Some chloride channels are activated only by voltage (i.e., voltage-gated), while others are activated by Ca2+, other extracellular ligands, or pH.
The CLC family of chloride channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three CLC subfamilies are found in animals. CLCN1 is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney. These proteins contain two CBS domains. Chloride channels are also important for maintaining safe ion concentrations within plant cells.
Structure and mechanism
The CLC channel structure has not yet been resolved, however the structure of the CLC exchangers has been resolved by x-ray crystallography. Because the primary structure of the channels and exchangers are so similar, most assumptions about the structure of the channels are based on the structure established for the bacterial exchangers.
Each channel or exchanger is composed of two similar subunitsâ€”a dimerâ€”each subunit containing one pore. The proteins are formed from two copies of the same proteinâ€”a homodimerâ€”though scientists have artificially combined subunits from different channels to form heterodimers. Each subunit binds ions independently of the other, meaning conduction or exchange occur independently in each subunit.
Each subunit consists of two related halves oriented in opposite directions, forming an â€˜antiparallelâ€™ structure. These halves come together to form the anion pore. The pore has a filter through which chloride and other anions can pass, but lets little else through. These water-filled pores filter anions via three binding sitesâ€”Sint, Scen, and Sextâ€”which bind chloride and other anions. The names of these binding sites correspond to their positions within the membrane. Sint is exposed to intracellular fluid, Scen lies inside the membrane or in the center of the filter, and Sext is exposed to extracellular fluid. Each binding site binds different chloride anions simultaneously. In the exchangers, these chloride ions do not interact strongly with one another, due to compensating interactions with the protein. In the channels, the protein does not shield chloride ions at one binding site from the neighboring negatively charged chlorides. Each negative charge exerts a repulsive force on the negative charges next to it. Researchers have suggested that this mutual repulsion contributes to the high rate of conduction through the pore.
CLC transporters shuttle H+ across the membrane. The H+ pathway in CLC transporters utilizes two glutamate residuesâ€”one on the extracellular side, Gluex, and one on the intracellular side, Gluin. Gluex also serves to regulate chloride exchange between the protein and extracellular solution. This means that the chloride and the proton share a common pathway on the extracellular side, but diverge on the intracellular side.
CLC channels also have dependence on H+, but for gating rather than Clâˆ’ exchange. Instead of utilizing gradients to exchange two Clâˆ’ for one H+, the CLC channels transport one H+ while simultaneously transporting millions of anions. This corresponds with one cycle of the slow gate.
Eukaryotic CLC channels also contain cytoplasmic domains. These domains have a pair of CBS motifs, whose function is not fully characterized yet. Though the precise function of these domains is not fully characterized, their importance is illustrated by the pathologies resulting from their mutation. Thomsen's disease, Dent's disease, infantile malignant osteopetrosis, and Bartter's syndrome are all genetic disorders due to such mutations.
At least one role of the cytoplasmic CBS domains regards regulation via adenosine nucleotides. Particular CLC transporters and proteins have modulated activity when bound with ATP, ADP, AMP, or adenosine at the CBS domains. The specific effect is unique to each protein, but the implication is that certain CLC transporters and proteins are sensitive to the metabolic state of the cell.
The Scen acts as the primary selectivity filter for most CLC proteins, allowing the following anions to pass through, from most selected to least: SCNâˆ’, Clâˆ’, Brâˆ’, NOâˆ’
3, Iâˆ’. Altering a serine residue at the selectivity filter, labeled Sercen, to a different amino acid alters the selectivity.
Gating and kinetics
Gating occurs through two mechanisms: protopore or fast gating and common or slow gating. Common gating involves both protein subunits closing their pores at the same time (cooperation), while protopore gating involves independent opening and closing of each pore. As the names imply, fast gating occur at a much faster rate than slow gating. Precise molecular mechanisms for gating are still being studied.
For the channels, when the slow gate is closed, no ions permeate through the pore. When the slow gate is open, the fast gates open spontaneously and independently of one another. Thus, the protein could have both gates open, or both gates closed, or just one of the two gates open. Single-channel patch-clamp studies demonstrated this biophysical property even before the dual-pore structure of CLC channels had been resolved. Each fast gate opens independently of the other and the ion conductance measured during these studies reflects a binomial distribution.
H+ transport promotes opening of the common gate in CLC channels. For every opening and closing of the common gate, one H+ is transported across the membrane. The common gate is also affected by the bonding of adenosine nucleotides to the intracellular CBS domains. Inhibition or activation of the protein by these domains is specific to each protein.
The CLC channels allow chloride to flow down its electrochemical gradient, when open. These channels are expressed on the cell membrane. CLC channels contribute to the excitability of these membranes as well as transport ions across the membrane.
The CLC exchangers are localized to intracellular components like endosomes or lysosomes and help regulate the pH of their compartments.
Bartter's syndrome, which is associated with renal salt wasting and hypokalemic alkalosis, is due to the defective transport of chloride ions and associated ions in the thick ascending loop of Henle. CLCNKB has been implicated.
Members of Epithelial Chloride Channel (E-ClC) Family (TC# 1.A.13) catalyze bidirectional transport of chloride ions. Mammals have multiple isoforms (at least 6 different gene products plus splice variants) of epithelial chloride channel proteins, catalogued into the Chloride channel accessory (CLCA) family. The first member of this family to be characterized was a respiratory epithelium, Ca2+-regulated, chloride channel protein isolated from bovine tracheal apical membranes. It was biochemically characterized as a 140 kDa complex. The bovine EClC protein has 903 amino acids and four putative transmembrane segments. The purified complex, when reconstituted in a planar lipid bilayer, behaved as an anion-selective channel. It was regulated by Ca2+ via a calmodulin kinase II-dependent mechanism. Distant homologues may be present in plants, ciliates and bacteria, Synechocystis and Escherichia coli, so at least some domains within E-ClC family proteins have an ancient origin.
|Chloride intracellular ion channel|
The Chloride Intracellular Ion Channel (CLIC) Family (TC# 1.A.12) consists of six conserved proteins in humans (CLIC1, CLIC2, CLIC3, CLIC4, CLIC5, CLIC6). Members exist as both monomeric soluble proteins and integral membrane proteins where they function as chloride-selective ion channels. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. They are a member of the glutathione S-transferase (GST) superfamily.
They possess one or two putative transmembrane Î±-helical segments (TMSs). The bovine p64 protein is 437 amino acyl residues in length and has the two putative TMSs at positions 223-239 and 367-385. The N- and C-termini are cytoplasmic, and the large central luminal loop may be glycosylated. The human nuclear protein (CLIC1 or NCC27) is much smaller (241 residues) and has only one putative TMS at positions 30-36. It is homologous to the second half of p64.
Structural studies showed that in the soluble form, CLIC proteins adopt a GST fold with an active site exhibiting a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. Al Khamici et al. demonstrated that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. This activity may regulate CLIC ion channel function.
The generalized transport reaction believed to be catalyzed chloride channels is:
- Clâˆ’ (cytoplasm) â†’ Clâˆ’ (intraorganellar space)
CFTR is a chloride channel belonging to the superfamily of ABC transporters. Each channel has two transmembrane domains and two nucleotide binding domains. ATP binding to both nucleotide binding domains causes changes these domains to associate, further causing changes that open up the ion pore. When ATP is hydrolyzed, the nucleotide binding domains dissociate again and the pore closes.
Cystic fibrosis is caused by mutations in the CFTR gene on chromosome 7, the most common mutation being deltaF508 (a deletion of a codon coding for phenylalanine, which occupies the 508th amino acid position in the normal CFTR polypeptide). Any of these mutations can prevent the proper folding of the protein and induce its subsequent degradation, resulting in decreased numbers of chloride channels in the body. This causes the buildup of mucus in the body and chronic infections.
Other chloride channels and families
- Jentsch TJ, Stein V, Weinreich F, Zdebik AA (April 2002). "Molecular structure and physiological function of chloride channels". Physiological Reviews. 82 (2): 503â€“68. doi:10.1152/physrev.00029.2001. PMID 11917096.
- Suzuki M, Morita T, Iwamoto T (January 2006). "Diversity of Cl(-) channels". Cellular and Molecular Life Sciences. 63 (1): 12â€“24. doi:10.1007/s00018-005-5336-4. PMC 2792346. PMID 16314923.
- StÃ¶lting G, Fischer M, Fahlke C (January 2014). "CLC channel function and dysfunction in health and disease". Frontiers in Physiology. 5: 378. doi:10.3389/fphys.2014.00378. PMC 4188032. PMID 25339907.
- Li WY, Wong FL, Tsai SN, Phang TH, Shao G, Lam HM (June 2006). "Tonoplast-located GmCLC1 and GmNHX1 from soybean enhance NaCl tolerance in transgenic bright yellow (BY)-2 cells". Plant, Cell & Environment. 29 (6): 1122â€“37. doi:10.1111/j.1365-3040.2005.01487.x. PMID 17080938.
- Dutzler R (June 2007). "A structural perspective on ClC channel and transporter function". FEBS Letters. 581 (15): 2839â€“44. doi:10.1016/j.febslet.2007.04.016. PMID 17452037.
- Accardi A, Picollo A (August 2010). "CLC channels and transporters: proteins with borderline personalities". Biochimica et Biophysica Acta. 1798 (8): 1457â€“64. doi:10.1016/j.bbamem.2010.02.022. PMC 2885512. PMID 20188062.
- Planells-Cases R, Jentsch TJ (March 2009). "Chloride channelopathies" (PDF). Biochimica et Biophysica Acta. 1792 (3): 173â€“89. doi:10.1016/j.bbadis.2009.02.002. PMID 19708126.
- Evans SR, Thoreson WB, Beck CL (October 2004). "Molecular and functional analyses of two new calcium-activated chloride channel family members from mouse eye and intestine". The Journal of Biological Chemistry. 279 (40): 41792â€“800. doi:10.1074/jbc.M408354200. PMC 1383427. PMID 15284223.
- Agnel M, Vermat T, Culouscou JM (July 1999). "Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea". FEBS Letters. 455 (3): 295â€“301. doi:10.1016/s0014-5793(99)00891-1. PMID 10437792.
- Brunetti E, Filice C (June 1996). "Percutaneous aspiration in the treatment of hydatid liver cysts". Gut. 38 (6): 936. doi:10.1136/gut.38.6.936. PMC 1383206. PMID 8984037.
- Singh H, Ashley RH (2007-02-01). "CLIC4 (p64H1) and its putative transmembrane domain form poorly selective, redox-regulated ion channels". Molecular Membrane Biology. 24 (1): 41â€“52. doi:10.1080/09687860600927907. PMID 17453412.
- Al Khamici H, Brown LJ, Hossain KR, Hudson AL, Sinclair-Burton AA, Ng JP, Daniel EL, Hare JE, Cornell BA, Curmi PM, Davey MW, Valenzuela SM (2015-01-01). "Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity". PLOS One. 10 (1): e115699. doi:10.1371/journal.pone.0115699. PMC 4291220. PMID 25581026.
- Gadsby DC, Vergani P, CsanÃ¡dy L (March 2006). "The ABC protein turned chloride channel whose failure causes cystic fibrosis". Nature. 440 (7083): 477â€“83. doi:10.1038/nature04712. PMC 2720541. PMID 16554808.
- Schmidt-Rose T, Jentsch TJ (August 1997). "Reconstitution of functional voltage-gated chloride channels from complementary fragments of CLC-1". The Journal of Biological Chemistry. 272 (33): 20515â€“21. doi:10.1074/jbc.272.33.20515. PMID 9252364.
- Zhang J, George AL, Griggs RC, Fouad GT, Roberts J, KwieciÅ„ski H, Connolly AM, PtÃ¡cek LJ (October 1996). "Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita". Neurology. 47 (4): 993â€“8. doi:10.1212/wnl.47.4.993. PMID 8857733.
- Mindell JA, Maduke M (2001). "ClC chloride channels". Genome Biology. 2 (2): REVIEWS3003. doi:10.1186/gb-2001-2-2-reviews3003. PMC 138906. PMID 11182894.
- Singh H (May 2010). "Two decades with dimorphic Chloride Intracellular Channels (CLICs)". FEBS Letters. 584 (10): 2112â€“21. doi:10.1016/j.febslet.2010.03.013. PMID 20226783.
- Chloride+channels at the US National Library of Medicine Medical Subject Headings (MeSH)
- UMich Orientation of Proteins in Membranes families/superfamily-10 - CLC chloride channels
As of this edit, this article uses content from "1.A.13 The Epithelial Chloride Channel (E-ClC) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed. As of this edit, this article uses content from "1.A.12 The Intracellular Chloride Channel (CLIC) Family", which is licensed in a way that permits reuse under the Creative Commons Attribution-ShareAlike 3.0 Unported License, but not under the GFDL. All relevant terms must be followed.
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.
Voltage gated chloride channel Provide feedback
This family of ion channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three ClC subfamilies are found in animals. ClC-1 (P35523) is involved in setting and restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney . These proteins contain two PF00571 domains.
Zhang J, George AL Jr, Griggs RC, Fouad GT, Roberts J, Kwiecinski H, Connolly AM, Ptacek LJ; , Neurology 1996;47:993-998.: Mutations in the human skeletal muscle chloride channel gene (CLCN1) associated with dominant and recessive myotonia congenita. PUBMED:8857733 EPMC:8857733
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001807
Chloride channels (CLCs) constitute an evolutionarily well-conserved family of voltage-gated channels that are structurally unrelated to the other known voltage-gated channels. They are found in organisms ranging from bacteria to yeasts and plants, and also to animals. Their functions in higher animals likely include the regulation of cell volume, control of electrical excitability and trans-epithelial transport [ PUBMED:9046241 ].
The first member of the family (CLC-0) was expression-cloned from the electric organ of Torpedo marmorata [ PUBMED:2174129 ], and subsequently nine CLC-like proteins have been cloned from mammals. They are thought to function as multimers of two or more identical or homologous subunits, and they have varying tissue distributions and functional properties. To date, CLC-0, CLC-1, CLC-2, CLC-4 and CLC-5 have been demonstrated to form functional Cl- channels; whether the remaining isoforms do so is either contested or unproven. One possible explanation for the difficulty in expressing activatable Cl- channels is that some of the isoforms may function as Cl- channels of intracellular compartments, rather than of the plasma membrane. However, they are all thought to have a similar transmembrane (TM) topology, initial hydropathy analysis suggesting 13 hydrophobic stretches long enough to form putative TM domains [ PUBMED:2174129 ]. Recently, the postulated TM topology has been revised, and it now seems likely that the CLCs have 10 (or possibly 12) TM domains, with both N- and C-termini residing in the cytoplasm [ PUBMED:9207144 ].
A number of human disease-causing mutations have been identified in the genes encoding CLCs. Mutations in CLCN1, the gene encoding CLC-1, the major skeletal muscle Cl- channel, lead to both recessively and dominantly-inherited forms of muscle stiffness or myotonia [ PUBMED:7581380 ]. Similarly, mutations in CLCN5, which encodes CLC-5, a renal Cl- channel, lead to several forms of inherited kidney stone disease [ PUBMED:8559248 ]. These mutations have been demonstrated to reduce or abolish CLC function.
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||voltage-gated chloride channel activity (GO:0005247)|
|Biological process||transmembrane transport (GO:0055085)|
|chloride transport (GO:0006821)|
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:
- the number of sequences which exhibit this architecture
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
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the UniProtKB sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
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.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
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.
|Seed source:||wublastp P37020/1-588|
|Number in seed:||105|
|Number in full:||18609|
|Average length of the domain:||340.20 aa|
|Average identity of full alignment:||24 %|
|Average coverage of the sequence by the domain:||54.01 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||22|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
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.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
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.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
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 Voltage_CLC domain has been found. There are 144 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 sequence.
Loading structure mapping...
AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.