Summary: Inward rectifier potassium channel

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Wikipedia: Inward-rectifier potassium ion channel
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Inward-rectifier potassium ion channel Edit Wikipedia article

Inward rectifier potassium channel

crystal structure of an inward rectifier potassium channel

Identifiers

Symbol

IRK

Pfam clan

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

Inward rectifier potassium channel N-terminal

Identifiers

Symbol

IRK_N

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

Inwardly rectifying potassium channels (K_ir, IRK) are a specific subset of potassium selective ion channels. To date, seven subfamilies have been identified in various mammalian cell types^[1] and they are also found in plants.^[2] They are the targets of multiple toxins, and malfunction of the channels has been implicated in several diseases.^[3]

[edit] Overview of inward rectification

Figure 1. Whole-cell current recordings of K_ir2 inwardly-rectifying potassium channels expressed in an HEK293 cell. (This is a strongly inwardly rectifying current. Downward deflections are inward currents, upward deflections outward currents, and the x-axis is time in seconds.) There are 13 responses superimposed in this image. The bottom-most trace is current elicited by a voltage step to negative 60mV, and the top-most to positive 60mV, relative to the resting potential, which is close to the K⁺ reversal potential in this experimental system. Other traces are in 10mV increments between the two.

A channel that is "inwardly-rectifying" is one that passes current (positive charge) more easily in the inward direction (into the cell). It is thought that this current may play an important role in regulating neuronal activity, by helping to establish the resting membrane potential of the cell.

By convention, inward current is displayed in voltage clamp as a downward deflection, while an outward current (positive charge moving out of the cell) is shown as an upward deflection. At membrane potentials negative to potassium's reversal potential, inwardly rectifying K⁺ channels support the flow of positively charged K⁺ ions into the cell, pushing the membrane potential back to the resting potential. This can be seen in figure 1: when the membrane potential is clamped negative to the channel's resting potential (e.g. -60 mV), inward current flows (i.e. positive charge flows into the cell). However, when the membrane potential is set positive to the channel's resting potential (e.g. +60 mV), these channels pass very little charge out of the cell. Simply put, this channel passes much more current in the inward direction than the outward one. Note that these channels are not perfect rectifiers, as they can pass some outward current in the voltage range up to about 30 mV above resting potential.

These channels differ from the potassium channels that are typically responsible for repolarizing a cell following an action potential, such as the delayed rectifier and A-type potassium channels. Those more "typical" potassium channels preferentially carry outward (rather than inward) potassium currents at depolarized membrane potentials, and may be thought of as "outwardly rectifying." When first discovered, inward rectification was named "anomalous rectification" to distinguish it from outward potassium currents.^[4]

Inward rectifiers also differ from tandem pore domain potassium channels, which are largely responsible for "leak" K⁺ currents.^[5] Some inward rectifiers, termed "weak inward rectifiers," carry measurable outward K⁺ currents at voltages positive to the K⁺ reversal potential (corresponding to, but larger than, the small currents above the 0 nA line in figure 1). They, along with the "leak" channels, establish the resting membrane potential of the cell. Other inwardly rectifying channels, termed "strong inward rectifiers," carry very little outward current at all, and are mainly active at voltages negative to the reversal potential, where they carry inward current (the much larger currents below the 0 nA line in figure 1).^[6]

[edit] Mechanism of inward rectification

The phenomenon of inward rectification of K_ir channels is the result of high-affinity block by endogenous polyamines, namely spermine, as well as magnesium ions, that plug the channel pore at positive potentials, resulting in a decrease in outward currents. This voltage-dependent block by polyamines causes currents to be conducted well only in the inward direction. While the principal idea of polyamine block is understood, the specific mechanisms are still controversial.

[edit] Role of K_ir channels

K_ir channels are found in multiple cell types, including macrophages, cardiac and kidney cells, leukocytes, neurons, and endothelial cells. By mediating a small depolarizing K⁺ current at negative membrane potentials, they help establish resting membrane potential, and in the case of the K_ir3 group, they help mediate inhibitory neurotransmitter responses, but their roles in cellular physiology vary across cell types:

Location	Function
cardiac myocytes	K_ir channels close upon depolarization, slowing membrane repolarization and helping maintain a more prolonged cardiac action potential. This type of inward-rectifier channel is distinct from delayed rectifier K⁺ channels, which help repolarize nerve and muscle cells after action potentials; and potassium leak channels, which provide much of the basis for the resting membrane potential.
endothelial cells	K_ir channels are involved in regulation of nitric oxide synthase.
kidneys	K_ir export surplus potassium into collecting tubules for removal in the urine, or alternatively may be involved in the reuptake of potassium back into the body.
neurons and in heart cells	G-protein activated IRKs (K_ir3) are important regulators, modulated by neurotransmitters. A mutation in the GIRK2 channel leads to the weaver mouse mutation. "Weaver" mutant mice are ataxic and display a neuroinflammation-mediated degeneration of their dopaminergic neurons.^[7] Relative to non-ataxic controls, Weaver mutants have deficits in motor coordination and changes in regional brain metabolism.^[8] Weaver mice have been examined in labs interested in neural development and disease for over 30 years.
pancreatic beta cells	K_ATP channels (composed of K_ir6.2 and SUR1 subunits) control insulin release.

[edit] Biochemistry of K_ir channels

There are seven subfamilies of K_ir channels, denoted as K_ir1 - K_ir7.^[1] Each subfamily has multiple members (i.e. K_ir2.1, K_ir2.2, K_ir2.3, etc.) that have nearly identical amino acid sequences across known mammalian species.

K_ir channels are formed from as homotetrameric membrane proteins. Each of the four identical protein subunits is composed of two membrane-spanning alpha helices (M1 and M2). Heterotetramers can form between members of the same subfamily (i.e. K_ir2.1 and K_ir2.3) when the channels are overexpressed.

[edit] Diversity

Gene	Protein	Aliases	Associated subunits
KCNJ1	K_ir1.1	ROMK1	NHERF2
KCNJ2	K_ir2.1	IRK1	K_ir2.2, K_ir4.1, PSD-95, SAP97, AKAP79
KCNJ12	K_ir2.2	IRK2	K_ir2.1 and K_ir2.3 to form heteromeric channel, auxiliary subunit: SAP97, Veli-1, Veli-3, PSD-95
KCNJ4	K_ir2.3	IRK3	K_ir2.1 and K_ir2.3 to form heteromeric channel, PSD-95, Chapsyn-110/PSD-93
KCNJ14	K_ir2.4	IRK4	K_ir2.1 to form heteromeric channel
KCNJ3	K_ir3.1	GIRK1, KGA	K_ir3.2, K_ir3.4, K_ir3.5, K_ir3.1 is not functional by itself
KCNJ6	K_ir3.2	GIRK2	K_ir3.1, K_ir3.3, K_ir3.4 to form heteromeric channel
KCNJ9	K_ir3.3	GIRK3	K_ir3.1, K_ir3.2 to form heteromeric channel
KCNJ5	K_ir3.4	GIRK4	K_ir3.1, K_ir3.2, K_ir3.3
KCNJ10	K_ir4.1	K_ir1.2	K_ir4.2, K_ir5.1, and K_ir2.1 to form heteromeric channels
KCNJ15	K_ir4.2	K_ir1.3
KCNJ16	K_ir5.1	BIR 9
KCNJ8	K_ir6.1	K_ATP	SUR2B
KCNJ11	K_ir6.2	K_ATP	SUR1, SUR2A, and SUR2B
KCNJ13	K_ir7.1	K_ir1.4

[edit] Diseases related to K_ir channels

Persistent hyperinsulinemic hypoglycemia of infancy is related to autosomal recessive mutations in K_ir6.2. Certain mutations of this gene diminish the channel's ability to regulate insulin secretion, leading to hypoglycemia.
Bartter's syndrome can be caused by mutations in K_ir channels. This condition is characterized by the inability of kidneys to recycle potassium, causing low levels of potassium in the body.
Andersen's syndrome is a rare condition caused by multiple mutations of K_ir2.1. Depending on the mutation, it can be dominant or recessive. It is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features. (See also KCNJ2)
Barium poisoning is likely due to its ability to block K_ir channels.
Atherosclerosis (heart disease) may be related to K_ir channels. The loss of K_ir currents in endothelial cells is one of the first known indicators of atherogenesis (the beginning of heart disease).
Thyrotoxic hypokalaemic periodic paralysis has been linked to altered K_ir2.6 function.^[9]

[edit] See also

Neuroscience portal

[edit] References

^ ^a ^b Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA (2005). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol Rev 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID 16382105.
^ Hedrich, R.; Moran, O.; Conti, F.; Busch, H.; Becker, D.; Gambale, F.; Dreyer, I.; k�Ch, A. et al. (1995). "Inward rectifier potassium channels in plants differ from their animal counterparts in response to voltage and channel modulators". European Biophysics Journal 24 (2). doi:10.1007/BF00211406. edit
^ Abraham MR, Jahangir A, Alekseev AE, Terzic A (November 1, 1999). "Channelopathies of inwardly rectifying potassium channels". FASEB J 13 (14): 1901–10. PMID 10544173. http://www.fasebj.org/cgi/content/full/13/14/1901.
^ Bertil Hille (2001). Ion Channels of Excitable Membranes 3rd ed. (Sinauer: Sunderland, MA), p. 151. ISBN 0-87893-321-2.
^ Hille, p. 155.
^ Hille, p. 153.
^ Peng J, Xie L, Stevenson FF et al. (2006). "Nigrostriatal dopaminergic neurodegeneration in the weaver mouse is mediated via neuroinflammation and alleviated by minocycline administration". J. Neurosci. 26 (45): 11644–51. doi:10.1523/JNEUROSCI.3447-06.2006. PMID 17093086.
^ Strazielle C, Deiss V, Naudon L, Raisman-Vozari R, Lalonde R. (2006). "Regional brain variations of cytochrome oxidase activity and motor coordination in Girk2(Wv) (Weaver) mutant mice.". Neuroscience 142 (2): 437–49. doi:10.1016/j.neuroscience.2006.06.011. PMID 16844307.
^ [1]

[edit] Further reading

Bertil Hille (2001). Ion Channels of Excitable Membranes 3rd ed. (Sinauer: Sunderland, MA), pp. 149–154. ISBN 0-87893-321-2.

[edit] External links

Inward Rectifier Potassium Channels at the US National Library of Medicine Medical Subject Headings (MeSH).
"Inwardly Recifying Potassium Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/IC/FamilyMenuForward?familyId=17.
UMich Orientation of Proteins in Membranes families/family-85 - Spatial positions of inward rectifier potassium channels in membranes.

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

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.

Inward rectifier potassium channel Provide feedback

No Pfam abstract.

Literature references

Doupnik CA, Davidson N, Lester HA; , Curr Opin Neurobiol 1995;5:268-277.: The inward rectifier potassium channel family. PUBMED:7580148 EPMC:7580148

External database links

MIM:	601678
PANDIT:	PF01007
Pseudofam:	PF01007
SCOP:	1n9p
SYSTERS:	IRK
Transporter classification:	1.A.2

This tab holds annotation information from the InterPro database.

InterPro entry IPR013521

Potassium channels are the most diverse group of the ion channel family [PUBMED:1772658, PUBMED:1879548]. They are important in shaping the action potential, and in neuronal excitability and plasticity [PUBMED:2451788]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [PUBMED:2555158]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.

These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K⁺ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers [PUBMED:2448635]. In eukaryotic cells, K⁺ channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [PUBMED:1373731]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [PUBMED:11178249].

All K⁺ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K⁺ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K⁺ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K⁺ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K⁺ channels; and three types of calcium (Ca)-activated K⁺ channels (BK, IK and SK) [PUBMED:11178249]. The 2TM domain family comprises inward-rectifying K⁺ channels. In addition, there are K⁺ channel alpha-subunits that possess two P-domains. These are usually highly regulated K⁺ selective leak channels.

Inwardly-rectifying potassium channels (Kir) are the principal class of two-TM domain potassium channels. They are characterised by the property of inward-rectification, which is described as the ability to allow large inward currents and smaller outward currents. Inwardly rectifying potassium channels (Kir) are responsible for regulating diverse processes including: cellular excitability, vascular tone, heart rate, renal salt flow, and insulin release [PUBMED:10102275]. To date, around twenty members of this superfamily have been cloned, which can be grouped into six families by sequence similarity, and these are designated Kir1.x-6.x [PUBMED:7580148, PUBMED:10449331].

Cloned Kir channel cDNAs encode proteins of between ~370-500 residues, both N- and C-termini are thought to be cytoplasmic, and the N terminus lacks a signal sequence. Kir channel alpha subunits possess only 2TM domains linked with a P-domain. Thus, Kir channels share similarity with the fifth and sixth domains, and P-domain of the other families. It is thought that four Kir subunits assemble to form a tetrameric channel complex, which may be hetero- or homomeric [PUBMED:10102275].

Domain organisation

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Pfam Clan

This family is a member of clan Ion_channel (CL0030), which contains the following 8 members:

GLTSCR1 Ion_trans Ion_trans_2 IRK KdpA Lig_chan PKD_channel TrkH

Alignments

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	Seed (13)	Full (1452)	Representative proteomes				NCBI (1256)	Meta (32)
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Format an alignment

	Seed (13)	Full (1452)	Representative proteomes				NCBI (1256)	Meta (32)
	Seed (13)	Full (1452)	RP15 (170)	RP35 (277)	RP55 (492)	RP75 (764)	NCBI (1256)	Meta (32)
Alignment:
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	Seed (13)	Full (1452)	Representative proteomes				NCBI (1256)	Meta (32)
	Seed (13)	Full (1452)	RP15 (170)	RP35 (277)	RP55 (492)	RP75 (764)	NCBI (1256)	Meta (32)
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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Pfam-B_18 (release 3.0)

Previous IDs:

none

Type:

Family

Author:

Finn RD, Bateman A

Number in seed:

13

Number in full:

1452

Average length of the domain:

284.90 aa

Average identity of full alignment:

37 %

Average coverage of the sequence by the domain:

78.63 %

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	20.1	20.1
Trusted cut-off	20.1	20.1
Noise cut-off	20.0	20.0

Model length:

337

Family (HMM) version:

15

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Species distribution

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How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

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

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IRK

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 IRK domain has been found. There are 52 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: IRK (PF01007)

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