Summary: Neurotransmitter-gated ion-channel transmembrane region
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 "Ligand-gated ion 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 firstname.lastname@example.org 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.
Ligand-gated ion channel Edit Wikipedia article
|Neurotransmitter-gated ion-channel transmembrane region|
Ligand-gated ion channel
Ligand-gated ion channels (LGICs) are a group of transmembrane ion channel proteins which open to allow ions such as Na+, K+, Ca2+, or Cl- to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter.
These proteins are typically composed of at least two different domains: a transmembrane domain which includes the ion pore, and an extracellular domain which includes the ligand binding location (an allosteric binding site). This modularity has enabled a 'divide and conquer' approach to finding the structure of the proteins (crystallising each domain separately). The function of such receptors located at synapses is to convert the chemical signal of presynaptically released neurotransmitter directly and very quickly into a postsynaptic electrical signal. Many LGICs are additionally modulated by allosteric ligands, by channel blockers, ions, or the membrane potential. LGICs are classified into three superfamilies which lack evolutionary relationship: Cys-loop receptors, Ionotropic glutamate receptors and ATP-gated channels.
LGICs can be contrasted with metabotropic receptors (which use second messengers), voltage-gated ion channels (which open and close depending on membrane potential), and stretch-activated ion channels (which open and close depending on mechanical deformation of the cell membrane).
The cys-loop receptors are named after a characteristic loop formed by a disulfide bond between two cysteine residues in the N terminal extracellular domain. They are subdivided with respect to the type of ion that they conduct (anionic or cationic) and further into families defined by the endogenous ligand. They are usually pentameric with each subunit containing 4 transmembrane helices constituting the transmembrane domain, and a beta sheet sandwich type, extracellular, N terminal, ligand binding domain. Some also contain an intracellular domain like shown in the image.
The prototypic ligand-gated ion channel is the nicotinic acetylcholine receptor. It consists of a pentamer of protein subunits (typically ααβγδ), with two binding sites for acetylcholine (one at the interface of each alpha subunit). When the acetylcholine binds it alters the receptor's configuration (twists the T2 helices which moves the leucine residues, which block the pore, out of the channel pathway) and causes the constriction in the pore of approximately 3 angstroms to widen to approximately 8 angstroms so that ions can pass through. This pore allows Na+ ions to flow down their electrochemical gradient into the cell. With a sufficient number of channels opening at once, the inward flow of positive charges carried by Na+ ions depolarizes the postsynaptic membrane sufficiently to initiate an action potential.
While single-cell organisms like bacteria would have little apparent need for the transmission of an action potential, a bacterial homologue to an LGIC has been identified, hypothesized to act none the less as a chemoreceptor. This prokaryotic nAChR variant is know as the GLIC receptor, after the species in which it was identified; Gloeobacter Ligand-gated Ion Channel.
Vertebrate Anionic Cys-loop Receptors
|CAE2, ECA2, GEFSP3|
Vertebrate Cationic Cys-loop Receptors
protein name 
|ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMS
|CMS2A, SCCMS, ACHRB, CHRNB, CMS1D
|delta||δ||CHRND||ACHRD, CMS2A, FCCMS, SCCMS|
|epsilon||ε||CHRNE||ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS|
|Zinc-activated ion channel
|ZAC||ZACN||ZAC1, L2m LGICZ, LGICZ1|
Ionotropic glutamate receptors (iGluR)
The ionotropic glutamate receptors bind the neurotransmitter glutamate. They form tetramers with each subunit consisting of an extracellular amino terminal domain (ATD, which is involved tetramer assembly), an extracellular ligand binding domain (LBD, which binds glutamate), and a transmembrane domain (TMD, which forms the ion channel). The transmembrane domain of each subunit contains three transmembrane helices as well as a half membrane helix with a reentrant loop. The structure of the protein starts with the ATD at the N terminus followed by the first half of the LBD which is interrupted by helix 1,2 and 3 of the TMD before continuing with the final half of the LBD and then finishing with helix 4 of the TMD at the C terminus. This means there are three links between the TMD and the extracellular domains. Each subunit of the tetramer has a binding site for glutamate formed by the two LBD sections forming a clamshell like shape. Only two of these sites in the tetramer need to be occupied to open the ion channel. The pore is mainly formed by the half helix 2 in a way which resembles an inverted potassium channel.
protein name 
|GLUA1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1
GLUA2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2
GLUA3, GluR3, GluRC, GluR-C, GluR-K3
GLUA4, GluR4, GluRD, GluR-D
|GLUK5, GluR5, GluR-5, EAA3
GLUK6, GluR6, GluR-6, EAA4
GLUK7, GluR7, GluR-7, EAA5
GLUK1, KA1, KA-1, EAA1
GLUK2, KA2, KA-2, EAA2
|GLUN1, NMDA-R1, NR1, GluRξ1
|GLUN2A, NMDA-R2A, NR2A, GluRε1
GLUN2B, NMDA-R2B, NR2B, hNR3, GluRε2
GLUN2C, NMDA-R2C, NR2C, GluRε3
GLUN2D, NMDA-R2D, NR2D, GluRε4
|GLUN3A, NMDA-R3A, NMDAR-L, chi-1
protein name 
Phosphatidylinositol 4,5-bisphosphate (PIP2) binds to and directly agonizes Inward rectifying potassium channels(Kir). PIP2 is a plasma membrane lipid and its definitive role in gating ion channels was only recently demonstrated by X-ray crystallography.
Ligand-gated ion channels are likely to be the major site at which anaesthetic agents and ethanol have their effects, although unequivocal evidence of this is yet to be established. In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.
- "ligand-gated channel" at Dorland's Medical Dictionary
- Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed. Sinauer Associates. pp. 156–7. ISBN 978-0-87893-697-7.
- Connolly CN, Wafford KA (2004). "The Cys-loop superfamily of ligand-gated ion channels: the impact of receptor structure on function". Biochem. Soc. Trans. 32 (Pt3): 529–34. doi:10.1042/BST0320529. PMID 15157178.
- Cascio M (2004). "Structure and function of the glycine receptor and related nicotinicoid receptors". J. Biol. Chem. 279 (19): 19383–6. doi:10.1074/jbc.R300035200. PMID 15023997.
- Tasneem A, Iyer L, Jakobsson E, Aravind L (2004). "Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels". Genome Biology 6 (1): R4. doi:10.1186/gb-2004-6-1-r40. PMC 549065. PMID 15642096.
- Collingridge GL, Olsen RW, Peters J, Spedding M (January 2009). "A nomenclature for ligand-gated ion channels". Neuropharmacology 56 (1): 2–5. doi:10.1016/j.neuropharm.2008.06.063. PMC 2847504. PMID 18655795.
- Olsen RW, Sieghart W (September 2008). "International Union of Pharmacology. LXX. Subtypes of γ-Aminobutyric AcidA Receptors: Classification on the Basis of Subunit Composition, Pharmacology, and Function. Update". Pharmacol. Rev. 60 (3): 243–60. doi:10.1124/pr.108.00505. PMC 2847512. PMID 18790874.
- Hansen SB, Tao X, MacKinnon R (September 2011). "Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2". Nature 477 (7365): 495–8. doi:10.1038/nature10370. PMC 3324908. PMID 21874019. Unknown parameter
|bib code=ignored (help);
- Krasowski MD, Harrison NL (1999). "General anaesthetic actions on ligand-gated ion channels". Cell. Mol. Life Sci. 55 (10): 1278–303. doi:10.1007/s000180050371. PMC 2854026. PMID 10487207.
- Dilger JP (2002). "The effects of general anaesthetics on ligand-gated ion channels". Br J Anaesth 89 (1): 41–51. doi:10.1093/bja/aef161. PMID 12173240.
- Harris RA, Mihic SJ, Dildy-Mayfield JE, Machu TK (1995). "Actions of anesthetics on ligand-gated ion channels: role of receptor subunit composition" (abstract). FASEB J. 9 (14): 1454–62. PMID 7589987.
- Ligand-Gated Ion Channel database at European Bioinformatics Institute. Verified availability April 11, 2007.
- "Revised Recommendations for Nomenclature of Ligand-Gated Ion Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
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.
Neurotransmitter-gated ion-channel transmembrane region Provide feedback
This family includes the four transmembrane helices that form the ion channel.
Nury H, Bocquet N, Le Poupon C, Raynal B, Haouz A, Corringer PJ, Delarue M;, J Mol Biol. 2009; [Epub ahead of print]: Crystal Structure of the Extracellular Domain of a Bacterial Ligand-Gated Ion Channel. PUBMED:19917292 EPMC:19917292
Internal database links
External database links
|PRINTS:||PR00252 PR00253 PR00254|
This tab holds annotation information from the InterPro database.
InterPro entry IPR006029
Neurotransmitter ligand-gated ion channels are transmembrane receptor-ion channel complexes that open transiently upon binding of specific ligands, allowing rapid transmission of signals at chemical synapses [PUBMED:1721053, PUBMED:1846404]. Five of these ion channel receptor families have been shown to form a sequence-related superfamily:
- Nicotinic acetylcholine receptor (AchR), an excitatory cation channel in vertebrates and invertebrates; in vertebrate motor endplates it is composed of alpha, beta, gamma and delta/epsilon subunits; in neurons it is composed of alpha and non-alpha (or beta) subunits [PUBMED:18446614].
- Glycine receptor, an inhibitory chloride ion channel composed of alpha and beta subunits [PUBMED:15383648].
- Gamma-aminobutyric acid (GABA) receptor, an inhibitory chloride ion channel; at least four types of subunits (alpha, beta, gamma and delta) are known [PUBMED:18760291].
- Serotonin 5HT3 receptor, of which there are seven major types (5HT3-5HT7) [PUBMED:10026168].
- Glutamate receptor, an excitatory cation channel of which at least three types have been described (kainate, N-methyl-D-aspartate (NMDA) and quisqualate) [PUBMED:15165736].
These receptors possess a pentameric structure (made up of varying subunits), surrounding a central pore. All known sequences of subunits from neurotransmitter-gated ion-channels are structurally related. They are composed of a large extracellular glycosylated N-terminal ligand-binding domain, followed by three hydrophobic transmembrane regions which form the ionic channel, followed by an intracellular region of variable length. A fourth hydrophobic region is found at the C-terminal of the sequence [PUBMED:1721053, PUBMED:1846404].
This domain represents four transmembrane helices of a variety of neurotransmitter-gated ion-channels.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
|Biological process||ion transport (GO:0006811)|
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 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.
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 NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics 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.
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
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.
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.
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.
|Author:||Bateman A, Sonnhammer ELL|
|Number in seed:||50|
|Number in full:||6256|
|Average length of the domain:||169.90 aa|
|Average identity of full alignment:||20 %|
|Average coverage of the sequence by the domain:||43.13 %|
|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:||11|
|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.
There are 2 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 Neur_chan_memb domain has been found. There are 162 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.
Loading structure mapping...