Summary: Neurotransmitter-gated ion-channel transmembrane region

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Wikipedia: Ligand-gated ion channel
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Ligand-gated ion channel Edit Wikipedia article

Neurotransmitter-gated ion-channel transmembrane region

Ligand-gated ion channel

Identifiers

Symbol

Neur_chan_memb

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

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),^[1] such as a neurotransmitter.^[2]

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).^[2]^[3]

[edit] Cys-loop receptors

Nicotinic acetylcholine receptor in closed state with predicted membrane boundaries shown, PDB 2BG9

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.^[4] Some also contain a 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.

Vertebrate Anionic Cys-loop Receptors

Type	Class	IUPHAR-recommended protein name^[5]	Gene	Previous names
GABA_A	alpha	α₁ α₂ α₃ α₄ α₅ α₆	GABRA1 GABRA2 GABRA3 GABRA4 GABRA5 GABRA6	EJM, ECA4
	beta	β₁ β₂ β₃	GABRB1 GABRB2 GABRB3	ECA5
	gamma	γ₁ γ₂ γ₃	GABRG1 GABRG2 GABRG3	CAE2, ECA2, GEFSP3
	delta	δ	GABRD
	epsilon	ε	GABRE
	pi	π	GABRP
	theta	θ	GABRQ
	rho	ρ₁ ρ₂ ρ₃	GABRR1 GABRR2 GABRR3	GABA_C^[6]
Glycine (GlyR)	alpha	α₁ α₂ α₃ α₄	GLRA1 GLRA2 GLRA3 GLRA4	STHE
Glycine (GlyR)	beta	β	GLRB

Vertebrate Cationic Cys-loop Receptors

Type	Class	IUPHAR-recommended protein name ^[5]	Gene	Previous names
Serotonin (5-HT)	5-HT₃	5-HT3A 5-HT3B 5-HT3C 5-HT3D 5-HT3E	HTR3A HTR3B HTR3C HTR3D HTR3E	5-HT_3A 5-HT_3B 5-HT_3C 5-HT_3D 5-HT_3E
Nicotinic acetylcholine (nAChR)	alpha	α₁ α₂ α₃ α₄ α₅ α₆ α₇ α₉ α₁₀	CHRNA1 CHRNA2 CHRNA3 CHRNA4 CHRNA5 CHRNA6 CHRNA7 CHRNA9 CHRNA10	ACHRA, ACHRD, CHRNA, CMS2A, FCCMS, SCCMS
	beta	β₁ β₂ β₃ β₄	CHRNB1 CHRNB2 CHRNB3 CHRNB4	CMS2A, SCCMS, ACHRB, CHRNB, CMS1D EFNL3, nAChRB2
	gamma	γ	CHRNG	ACHRG
	delta	δ	CHRND	ACHRD, CMS2A, FCCMS, SCCMS
	epsilon	ε	CHRNE	ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS
Zinc-activated ion channel (ZAC)		ZAC	ZACN	ZAC1, L2m LGICZ, LGICZ1

[edit] Ionotropic glutamate receptors (iGluR)

The AMPA receptor bound to a glutamate antagonist showing the amino terminal, ligand binding, and transmembrane domain, PDB 3KG2

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.

Type	Class	IUPHAR-recommended protein name ^[5]	Gene	Previous names
AMPA	GluA	GluA1 GluA2 GluA3 GluA4	GRIA1 GRIA2 GRIA3 GRIA4	GLU_A1, GluR1, GluRA, GluR-A, GluR-K1, HBGR1 GLU_A2, GluR2, GluRB, GluR-B, GluR-K2, HBGR2 GLU_A3, GluR3, GluRC, GluR-C, GluR-K3 GLU_A4, GluR4, GluRD, GluR-D
Kainate	GluK	GluK1 GluK2 GluK3 GluK4 GluK5	GRIK1 GRIK2 GRIK3 GRIK4 GRIK5	GLU_K5, GluR5, GluR-5, EAA3 GLU_K6, GluR6, GluR-6, EAA4 GLU_K7, GluR7, GluR-7, EAA5 GLU_K1, KA1, KA-1, EAA1 GLU_K2, KA2, KA-2, EAA2
NMDA	GluN	GluN1 NRL1A NRL1B	GRIN1 GRINL1A GRINL1B	GLU_N1, NMDA-R1, NR1, GluRξ1
		GluN2A GluN2B GluN2C GluN2D	GRIN2A GRIN2B GRIN2C GRIN2D	GLU_N2A, NMDA-R2A, NR2A, GluRε1 GLU_N2B, NMDA-R2B, NR2B, hNR3, GluRε2 GLU_N2C, NMDA-R2C, NR2C, GluRε3 GLU_N2D, NMDA-R2D, NR2D, GluRε4
		GluN3A GluN3B	GRIN3A GRIN3B	GLU_N3A, NMDA-R3A, NMDAR-L, chi-1 GLU_3B, NMDA-R3B
‘Orphan’	(GluD)	GluD1 GluD2	GRID1 GRID2	GluRδ1 GluRδ2

[edit] ATP-gated channels

Figure 1. Schematic representation showing the membrane topology of a typical P2X receptor subunit. First and second transmembrane domains are labeled TM1 and TM2.

Main article: P2X receptor

ATP-gated channels open in response to binding the nucleotide ATP. They form trimers with two transmembrane helices per subunit and both the C and N termini on the intracellular side.

Type	Class	IUPHAR-recommended protein name ^[5]	Gene	Previous names
P2X	N/A	P2X1 P2X2 P2X3 P2X4 P2X5 P2X6 P2X7	P2RX1 P2RX2 P2RX3 P2RX4 P2RX5 P2RX6 P2RX7	P2X₁ P2X₂ P2X₃ P2X₄ P2X₅ P2X₆ P2X₇

[edit] Clinical relevance

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.^[7]^[8] In particular, the GABA and NMDA receptors are affected by anaesthetic agents at concentrations similar to those used in clinical anaesthesia.^[9]

[edit] See also

MCB portal

Neuroscience portal

Biology portal

[edit] References

^ "ligand-gated channel" at Dorland's Medical Dictionary
^ ^a ^b 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.
^ ^a ^b ^c ^d 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2847504/.
^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2847512/.
^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2854026/.
^ 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. http://www.fasebj.org/cgi/content/abstract/9/14/1454.

[edit] External links

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. http://www.iuphar-db.org/LGICNomenclature.jsp.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor (1, 2, 3) · Ryanodine receptor (1, 2, 3)

Voltage-gated	L-type/Ca_vα (1.1, 1.2, 1.3, 1.4) · N-type/Ca_vα2.2 · P-type/Ca_vα(2.1) · Q-type/Ca_vα2.1 · R-type/Ca_vα2.3 · T-type/Ca_vα(3.1, 3.2, 3.3) α₂δ-subunits (1, 2) · β-subunits (β1, β2, β3, β4) · γ-subunits (γ1, γ2, γ3, γ4) Cation channels of sperm (1, 2, 3, 4) · Two-pore channel (1, 2)

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel (α, β, γ, δ)

Proton-gated	Amiloride-sensitive cation channel (1, 2, 3, 4)

Voltage-gated	Na_vα (1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 7A) · Na_vβ (1, 2, 3, 4)

K⁺: Potassium channel

Calcium-activated	BK channel (α1, β1, β2, β3, β4) · SK channel (SK1, SK2, SK3) · IK channel (IK1) · K_Ca (1.1, 2.1, 2.2, 2.3, 3.1, 4.1, 4.2, 5.1)

Inward-rectifier	K_ATP · K_ir (1.1, 2.1, 2.2, 2.3, 2.4, 2.6) · GIRK/K_ir (3.1, 3.2, 3.3, 3.4) · K_ir (4.1, 4.2, 5.1, 6.1, 6.2, 7.1)

Tandem pore domain	K2P (1, 2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, 16, 17, 18)

Voltage-gated	K_vα1-6 (1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8) · (2.1, 2.2) · (3.1, 3.2, 3.3, 3.4) · (4.1, 4.2, 4.3) · (5.1) · (6.1, 6.2, 6.3, 6.4) K_vα7-12 (7.1, 7.2, 7.3, 7.4, 7.5) · (8.1, 8.2) · (9.1, 9.2, 9.3) · (10.1, 10.2) · (11.1/hERG, 11.2, 11.3) · (12.1, 12.2, 12.3) K_vβ (1, 2, 3) · KCNIP (1, 2, 3, 4) · minK/ISK · minK/ISK-like · MiRP (1, 2, 3) · Shaker gene

Miscellaneous

Cl^-: Chloride channel	ANO1 · Bestrophin (1, 2) · CFTR · CLCA (1, 2, 3, 4) · CLCN (1, 2, 3, 4, 5, 6, 7, KA, KB) · CLIC (1, 2, 3, 4, 5, 6, L1) · CLNS (1A, 1B)

H⁺: Proton channel	HVCN1

M⁺: CNG cation channel	α (1, 2, 3, 4) · β (1, 2, 3) · HCN (FC, 1, 2, 3, 4)

M⁺: TRP cation channel	TRPA (1) · TRPC (1, 2, 3, 4, 4AP, 5, 6, 7) · TRPM (1, 2, 3, 4, 5, 6, 7, 8) · TRPML (1, 2, 3) · TRPN · TRPP (1, 2) · TRPV (1, 2, 3, 4, 5, 6)

H₂O (+ solutes): Porin	Aquaporin (0, 1, 2, 3, 4, 5, 6, 7, 8, 9) · Voltage-dependent anion channel (1, 2, 3) · General bacterial porin family

Cytoplasm: Gap junction	Connexin: A (GJA1, GJA3, GJA4, GJA5, GJA8, GJA9, GJA10) · B (GJB1, GJB2, GJB3, GJB4, GJB5, GJB6, GJB7) · C (GJC1, GJC2, GJC3) · D (GJD2, GJD3, GJD4)) Innexin

By gating mechanism

Ion channel class	Ligand-gated · Light-gated · Voltage-gated · Stretch-activated

see also disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr

Ion channel, cell surface receptor: ligand-gated ion channels

Cys-loop receptors

5-HT/serotonin	5-HT₃ A B C D E

GABA	GABA_A α₁ α₂ α₃ α₄ α₅ α₆ β₁ β₂ β₃ γ₁ γ₂ γ₃ δ ε π θ GABA_A-ρ ρ₁ ρ₂ ρ₃

Glycine	α₁ α₂ α₃ α₄ β

Nicotinic acetylcholine	monomers: α1 α2 α3 α4 α5 α6 α7 α9 α10 β1 β2 β3 β4 δ ε pentamers: (α3)₂(β4)₃ (α4)₂(β2)₃ (α7)₅ (α1)₂(β4)₃ - Ganglion type (α1)₂β1δε - Muscle type

Zinc	Zinc-activated

Ionotropic glutamates

Ligand-gated only	AMPA (1 2 3 4) Kainate 1 2 3 4 5

Voltage- and ligand-gated	NMDA 1 2A 2B 2C 2D 3A 3B L1A L1B

‘Orphan’	GluD δ₁ δ₂

ATP-gated channels

Purinergic receptors	P2X 1 2 3 4 5 6 7

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

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.

Neurotransmitter-gated ion-channel transmembrane region Provide feedback

This family includes the four transmembrane helices that form the ion channel.

Literature references

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

SCOOP:

Asr Abi_2

External database links

PANDIT:	PF02932
PRINTS:	PR00252 PR00253 PR00254
PROSITE:	PDOC00209
Pseudofam:	PF02932
SCOP:	1cek
SYSTERS:	Neur_chan_memb
Transporter classification:	1.A.9

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.

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)
Biological process	ion transport (GO:0006811)

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

Viewing

You can see the alignments as HTML or in three different sequence viewers:

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Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

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Downloading

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View options

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 (50)	Full (6256)	Representative proteomes				NCBI (5277)	Meta (71)
	Seed (50)	Full (6256)	RP15 (922)	RP35 (1195)	RP55 (2303)	RP75 (3294)	NCBI (5277)	Meta (71)
Jalview	View	View	View	View	View	View	View	View
HTML	View		View	View	View	View
PP/heatmap	₁		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 (50)	Full (6256)	Representative proteomes				NCBI (5277)	Meta (71)
	Seed (50)	Full (6256)	RP15 (922)	RP35 (1195)	RP55 (2303)	RP75 (3294)	NCBI (5277)	Meta (71)
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 (50)	Full (6256)	Representative proteomes				NCBI (5277)	Meta (71)
	Seed (50)	Full (6256)	RP15 (922)	RP35 (1195)	RP55 (2303)	RP75 (3294)	NCBI (5277)	Meta (71)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	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.

HMM logo

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...

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:

Prosite

Previous IDs:

none

Type:

Family

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 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	23.1	23.1
Trusted cut-off	23.2	23.1
Noise cut-off	23.0	23.0

Model length:

237

Family (HMM) version:

11

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. 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:

superkingdom
kingdom
phylum
class
order
family
genus
species

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".

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.

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.

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

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.

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.

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.

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

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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.

Interactions

There are 2 interactions for this family. More...

Neur_chan_LBD Neur_chan_memb

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 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...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: Neur_chan_memb (PF02932)

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