| Type |
Details |
Score |
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
754
 |
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
747
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
285
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
759
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
191
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1224
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Leonetti MD |
| Year: |
2012 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel. |
| Volume: |
109 |
| Issue: |
47 |
| Pages: |
19274-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Piccini M |
| Year: |
1999 |
| Journal: |
Genomics |
| Title: |
KCNE1-like gene is deleted in AMME contiguous gene syndrome: identification and characterization of the human and mouse homologs. |
| Volume: |
60 |
| Issue: |
3 |
| Pages: |
251-7 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
143
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kurschner C |
| Year: |
1998 |
| Journal: |
Mol Cell Neurosci |
| Title: |
CIPP, a novel multivalent PDZ domain protein, selectively interacts with Kir4.0 family members, NMDA receptor subunits, neurexins, and neuroligins. |
| Volume: |
11 |
| Issue: |
3 |
| Pages: |
161-72 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
170
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Trudeau MC |
| Year: |
1999 |
| Journal: |
J Neurosci |
| Title: |
Functional analysis of a mouse brain Elk-type K+ channel. |
| Volume: |
19 |
| Issue: |
8 |
| Pages: |
2906-18 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
235
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
210
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
649
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1218
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
239
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
172
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
99
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
71
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
191
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1238
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
64
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
306
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
81
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1236
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
233
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
240
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
432
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
193
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
169
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
130
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
181
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1183
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
132
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
101
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1202
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
104
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
162
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
78
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
410
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
38
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1217
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
36
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
192
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
MacGregor GG |
| Year: |
1998 |
| Journal: |
Am J Physiol |
| Title: |
Partially active channels produced by PKA site mutation of the cloned renal K+ channel, ROMK2 (kir1.2). |
| Volume: |
275 |
| Issue: |
3 Pt 2 |
| Pages: |
F415-22 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Wang H |
| Year: |
2000 |
| Journal: |
Toxicol Appl Pharmacol |
| Title: |
Direct block of inward rectifier potassium channels by nicotine. |
| Volume: |
164 |
| Issue: |
1 |
| Pages: |
97-101 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Namba N |
| Year: |
1996 |
| Journal: |
FEBS Lett |
| Title: |
Kir2.2v: a possible negative regulator of the inwardly rectifying K+ channel Kir2.2. |
| Volume: |
386 |
| Issue: |
2-3 |
| Pages: |
211-4 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Ryan DP |
| Year: |
2010 |
| Journal: |
Cell |
| Title: |
Mutations in potassium channel Kir2.6 cause susceptibility to thyrotoxic hypokalemic periodic paralysis. |
| Volume: |
140 |
| Issue: |
1 |
| Pages: |
88-98 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Salkoff L |
| Year: |
2006 |
| Journal: |
Nat Rev Neurosci |
| Title: |
High-conductance potassium channels of the SLO family. |
| Volume: |
7 |
| Issue: |
12 |
| Pages: |
921-31 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Rizzi S |
| Year: |
2016 |
| Journal: |
J Comp Neurol |
| Title: |
Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain. |
| Volume: |
524 |
| Issue: |
10 |
| Pages: |
2093-116 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
McManus OB |
| Year: |
1995 |
| Journal: |
Neuron |
| Title: |
Functional role of the beta subunit of high conductance calcium-activated potassium channels. |
| Volume: |
14 |
| Issue: |
3 |
| Pages: |
645-50 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Nimigean CM |
| Year: |
1999 |
| Journal: |
J Gen Physiol |
| Title: |
The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states. |
| Volume: |
113 |
| Issue: |
3 |
| Pages: |
425-40 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Miyake A |
| Year: |
1999 |
| Journal: |
J Biol Chem |
| Title: |
New ether-Ã -go-go K(+) channel family members localized in human telencephalon. |
| Volume: |
274 |
| Issue: |
35 |
| Pages: |
25018-25 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Trudeau MC |
| Year: |
1995 |
| Journal: |
Science |
| Title: |
HERG, a human inward rectifier in the voltage-gated potassium channel family. |
| Volume: |
269 |
| Issue: |
5220 |
| Pages: |
92-5 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Chen J |
| Year: |
1999 |
| Journal: |
J Biol Chem |
| Title: |
Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation. |
| Volume: |
274 |
| Issue: |
15 |
| Pages: |
10113-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kramer JW |
| Year: |
1998 |
| Journal: |
Am J Physiol |
| Title: |
Modulation of potassium channel gating by coexpression of Kv2.1 with regulatory Kv5.1 or Kv6.1 alpha-subunits. |
| Volume: |
274 |
| Issue: |
6 Pt 1 |
| Pages: |
C1501-10 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Salinas M |
| Year: |
1997 |
| Journal: |
J Biol Chem |
| Title: |
Modes of regulation of shab K+ channel activity by the Kv8.1 subunit. |
| Volume: |
272 |
| Issue: |
13 |
| Pages: |
8774-80 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Shepard AR |
| Year: |
1999 |
| Journal: |
Am J Physiol |
| Title: |
Electrically silent potassium channel subunits from human lens epithelium. |
| Volume: |
277 |
| Issue: |
3 Pt 1 |
| Pages: |
C412-24 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Grant AW |
| Year: |
2003 |
| Journal: |
FEMS Microbiol Lett |
| Title: |
A novel aldo-keto reductase from Escherichia coli can increase resistance to methylglyoxal toxicity. |
| Volume: |
218 |
| Issue: |
1 |
| Pages: |
93-9 |
|
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•
•
•
•
|
| Publication |
| First Author: |
Desai KK |
| Year: |
2008 |
| Journal: |
Biochemistry |
| Title: |
A metabolic bypass of the triosephosphate isomerase reaction. |
| Volume: |
47 |
| Issue: |
31 |
| Pages: |
7983-5 |
|
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•
•
•
•
|
| Publication |
| First Author: |
Gulbis JM |
| Year: |
1999 |
| Journal: |
Cell |
| Title: |
Structure of a voltage-dependent K+ channel beta subunit. |
| Volume: |
97 |
| Issue: |
7 |
| Pages: |
943-52 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Leicher T |
| Year: |
1998 |
| Journal: |
J Biol Chem |
| Title: |
Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. |
| Volume: |
273 |
| Issue: |
52 |
| Pages: |
35095-101 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Rajan S |
| Year: |
2001 |
| Journal: |
J Biol Chem |
| Title: |
THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels. |
| Volume: |
276 |
| Issue: |
10 |
| Pages: |
7302-11 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
McCrossan ZA |
| Year: |
2009 |
| Journal: |
J Membr Biol |
| Title: |
Regulation of the Kv2.1 potassium channel by MinK and MiRP1. |
| Volume: |
228 |
| Issue: |
1 |
| Pages: |
1-14 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Abbott GW |
| Year: |
1999 |
| Journal: |
Cell |
| Title: |
MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. |
| Volume: |
97 |
| Issue: |
2 |
| Pages: |
175-87 |
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•
•
•
•
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| Publication |
| First Author: |
Abbott GW |
| Year: |
2001 |
| Journal: |
Cell |
| Title: |
MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. |
| Volume: |
104 |
| Issue: |
2 |
| Pages: |
217-31 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Schroeder BC |
| Year: |
2000 |
| Journal: |
Nature |
| Title: |
A constitutively open potassium channel formed by KCNQ1 and KCNE3. |
| Volume: |
403 |
| Issue: |
6766 |
| Pages: |
196-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Sanguinetti MC |
| Year: |
1996 |
| Journal: |
Nature |
| Title: |
Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel. |
| Volume: |
384 |
| Issue: |
6604 |
| Pages: |
80-3 |
|
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•
•
•
•
|
| Publication |
| First Author: |
Neyroud N |
| Year: |
1997 |
| Journal: |
Nat Genet |
| Title: |
A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. |
| Volume: |
15 |
| Issue: |
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186-9 |
|
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•
•
•
•
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Dvir M |
| Year: |
2014 |
| Journal: |
J Cell Sci |
| Title: |
Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIPâ‚‚. |
| Volume: |
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| Pages: |
3943-55 |
|
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•
•
•
•
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Blatz AL |
| Year: |
1986 |
| Journal: |
J Physiol |
| Title: |
Quantitative description of three modes of activity of fast chloride channels from rat skeletal muscle. |
| Volume: |
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| Pages: |
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|
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•
•
•
•
|
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Tseng-Crank J |
| Year: |
1994 |
| Journal: |
Neuron |
| Title: |
Cloning, expression, and distribution of functionally distinct Ca(2+)-activated K+ channel isoforms from human brain. |
| Volume: |
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•
•
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Romey G |
| Year: |
1984 |
| Journal: |
J Physiol (Paris) |
| Title: |
Apamin: a specific toxin to study a class of Ca2+-dependent K+ channels. |
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|
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•
•
•
•
|
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| First Author: |
Blatz AL |
| Year: |
1986 |
| Journal: |
Nature |
| Title: |
Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle. |
| Volume: |
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•
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•
•
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| First Author: |
Johnson SW |
| Year: |
1997 |
| Journal: |
Neurosci Lett |
| Title: |
Bicuculline methiodide potentiates NMDA-dependent burst firing in rat dopamine neurons by blocking apamin-sensitive Ca2+-activated K+ currents. |
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|
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•
•
•
•
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| First Author: |
Seutin V |
| Year: |
1999 |
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Trends Pharmacol Sci |
| Title: |
Recent advances in the pharmacology of quaternary salts of bicuculline. |
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•
•
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| Publication |
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Köhler M |
| Year: |
1996 |
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Science |
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Small-conductance, calcium-activated potassium channels from mammalian brain. |
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•
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Kubisch C |
| Year: |
1999 |
| Journal: |
Cell |
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KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. |
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96 |
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3 |
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437-46 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3). |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Kv2 voltage-dependent potassium channels (also known as the Shab family) are responsible for much of the delayed rectifier current in Drosophila melanogaster (Fruit fly) nervous system and muscle. However, in vertebrates, Kv2 channels have been shwon to be involved in the delayed rectifier currents of the heart and skeletal muscles. They are also thought to be important in determining intrinsic neuronal excitability in both mammals and non-mammals []. Kv2 channels can be further divided into 2 subtypes, designated Kv2.1 and Kv2.2.This entry represents the voltage-dependent Kv2 potassium channels. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 [].Kir1.1 channels (also known as ROMK1-6 and KAB-1) are thought to underlieK+secretion in the kidney. Their activity is modulated by intracellular pH, with acidosis inhibiting the channel. Both N- and C-termini are thought to be involved in this modulation. Mutations in Kir1.1 lead to Bartter's syndrome type III, an inherited kidney disorder, which leads to salt-wasting, hypokalaemia and metabolic acidosis. All of the mutations thathave been functionally characterised either abolish, or markedly reduce,Kir1.1 K+currents. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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 subdividedinto 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) []. 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 []. 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 [, ].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 [].The Kir1.2 channel (also known as Kir4.1, ROMK2, BIR10, KAB-2 and BIRK1) is found principally inthe brain, where it is widely distributed. It has also been found on satellite cells of the rat cochlear ganglia, and at low levels within the kidney. Kir1.2 channel activity is dependent upon phosphorylation-state, with two serine residues within the C terminus, likely the target of PKA protein kinase A, being involved []. Kir1.2 has recently been shown to interact with a novel PDZ domain-containing protein, CIPP []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 [].Kir2.1 (also known as IRK1) is thought to play a role in controlling theexcitability of brain and heart tissues. Immuno-localisation studies haverevealed it to be present on many cell types within the forebrain, includingneurones, macroglia, endothelial, ependymal and vascular smooth musclecells. Phosphatidylinositol 4,5-bisphosphate (PIP2) is thought to interactwith Kir2.1 (as well as several other Kir subunits) via a C-terminal motif,promoting channel activity. Recently it has been demonstrated that nicotinecan block Kir2.1 channels, this likely contributing to its ability topromote the occurrence of cardiac arrhythmias []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
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 []. 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 [, ].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 [].Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.Kir5 channels are significantly expressed in kidney, pancreas and thyroidgland, suggesting that they may be involved in the regulation of fluid andpH balance. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 [].Kir2.2 (also known as IRK2/BIR8), like other Kir2.x family members, hasbeen found to be expressed in the brain. Immuno-localisation studies haverevealed it is primarily expressed in the cerebellum, as opposed to theforebrain (cf. Kir1.1). It is also expressed to lower extents in thekidney, heart and skeletal muscle. When heterologously expressed in Xenopusoocytes, human Kir2.2 produced strong, inwardly rectifying K+currents.Co-expression of Kir2.2v (a closely related Kir2.x subunit) with Kir2.2caused an inhibition of induced K+currents, indicating that it likelyfunctions as a negative regulator of Kir2.2 [].This family also includes Kir2.6, which is nearly identical to Kir2.2 []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 [].Kir2.3 it thought to play a role in the maintenance of membrane potentialin both neurones and myocardium. It is highly expressed in the forebrain,and has a distinctly smaller ionic conductance than other Kir2.x familymembers. By comparison with other Kir2.x channels, sequence analysis showsit to have a larger putative extracellular loop (~15 more amino acidresidues) linking the first TM domain to the pore-forming (H5) domain, although the significance of this remains to be elucidated. Functionalstudies have revealed Kir2.3 channel activity to be modulated by channelphosphorylation, oxidation state, and changes in intracellular andextracellular pH. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 [].The Kir3.x channel family is gated by G-proteins following G-proteincoupled receptor (GPCR) activation. They are widely distributed inneuronal, atrial, and endocrine tissues and play key roles in generatinglate inhibitory postsynaptic potentials, slowing the heart rate andmodulating hormone release. They are directly activated by G-proteinbeta-gamma subunits released from G-protein heterotrimers of the G(i/o)family upon appropriate receptor stimulation.Kir3.1 channels are thought to form heteromers in vivo: in heart,consisting of Kir3.1 and Kir3.2, and in brain, Kir3.1 with Kir 3.4. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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 []. 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 [, ].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 [].The Kir3.x channel family is gated by G-proteins following G-proteincoupled receptor (GPCR) activation. They are widely distributed inneuronal, atrial, and endocrine tissues and play key roles in generatinglate inhibitory postsynaptic potentials, slowing the heart rate andmodulating hormone release. They are directly activated by G-proteinbeta-gamma subunits released from G-protein heterotrimers of the G(i/o)family upon appropriate receptor stimulation.Kir3.3 does not generate receptor-evoked, or constitutively-active K+currents, when heterologously expressed in Xenopus oocytes. It maytherefore contribute to Kir channel diversity by associating with otherKir3.x family members []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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. |
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| Protein Domain |
| Type: |
Family |
| Description: |
KCNE1 (Potassium voltage-gated channel subfamily E member 1, also known as Mink) subunits associate with KCNQ1 alpha subunits to form channels that are responsible for the IkS currents that determine the duration of the action potential in cardiac muscle []. Mutations in both of the genes encoding these subunits cause an inherited disorder that increases the risk of death from cardiac arrhythmia (long QT syndrome type 1) and Jervell and Lange-Nielsen syndrome, associated with congenital deafness [].Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). KCNE2 subunits associate with the eag-like HERG alpha subunits, which arethe pore-forming subunits of cardiac IKr channels. Channels formed solelyfrom HERG subunits display similar properties to native IKr channels;however, they differ in their gating and single channel conductance. Channels formed from both KCNE2 and HERG exhibit properties that are identical to those seen in native IKr channels. Three mutations in the KCNE2gene are associated with long QT syndrome and ventricular fibrillation. These mutations result in channels that open slower and close more rapidly,the net effect being a reduced K+ current []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.Two types of beta subunit (KCNE and KCNAB) are presently known to associate with voltage-gated alpha subunits (Kv, KCNQ and eag-like). However, not all combinations of alpha and beta subunits are possible. The KCNE family of K+ channel subunits are membrane glycoproteins that possess a single transmembrane (TM) domain. They share no structural relationship with the alpha subunit proteins, which possess pore forming domains. The subunits appear to have a regulatory function, modulating the kinetics and voltage dependence of the alpha subunits of voltage-dependent K+ channels. KCNE subunits are formed from short polypeptides of ~130 amino acids, and are divided into five subfamilies: KCNE1 (MinK/IsK), KCNE2 (MiRP1), KCNE3 (MiRP2), KCNE4 (MiRP3) and KCNE1L (AMMECR2). KCNE3 is known to associate with the pore forming subunits KCNQ1, KCNQ4,HERG and Kv3.4. KCNE3 forms complexes with Kv3.4 in skeletal muscle -KCNE3 mutations have been identified in families with skeletal muscledisorders []. In the intestine, KCNE3 associates with KCNQ1 to formchannels that are stimulated by cAMP and are thought to be involved insecretory diarrhoea and cystic fibrosis []. |
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| Protein Domain |
| Type: |
Domain |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The Kv family can be divided into several subfamilies on the basis of sequence similarity and function. Four of these subfamilies, Kv1 (Shaker), Kv2 (Shab), Kv3 (Shaw) and Kv4 (Shal), consist of pore-forming alpha subunits that associate with different types of beta subunit. Each alpha subunit comprises six hydrophobic TM domains with a P-domain between the fifth and sixth, which partially resides in the membrane. The fourth TM domain has positively charged residues at every third residue and acts as a voltage sensor, which triggers the conformational change that opens the channel pore in response to a displacement in membrane potential []. More recently, 4 new electrically-silent alpha subunits have been cloned: Kv5 (KCNF), Kv6 (KCNG), Kv8 and Kv9 (KCNS). These subunits do not themselves possess any functional activity, but appear to form heteromeric channels with Kv2 subunits, and thus modulate Shab channel activity []. When highly expressed, they inhibit channel activity, but at lower levels show more specific modulatory actions.The Shal potassium channel was found in Drosophila melanogaster (Fruit fly). Several vertebrate potassium channels with similar amino acid sequences were subsequently found and, together with the D. melanogaster Shal channel, now constitute the Kv4 family. These channels are the primary subunits contributing to transient, voltage-dependent potassium currents in the nervous system (A currents) and the heart (transient outward current), and are inhibited by free fatty acids []. This family can be further divided into 3 subfamilies, designated Kv4.1(KCND1), Kv4.2(KCND2) and Kv4.3(KCND3).This uncharacterised C-terminal domain is associated with the Shal (Kv4) potassium channel. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: the practically non-inactivating 'delayed' group and therapidly 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [].The human ether-a-go-go-related gene (HERG), cloned from hippocampus, shares 49% amino acid identity with EAG. It is also found in the heart, where it helps to control K+ efflux []. Mutations in HERG result in the disruption of the repolarising current and the disease LQT2 syndrome, an inheriteddisorder of cardiac repolarisation that predisposes affected individuals tolife-threatening arrhythmias []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type [].The EAG subfamily has been expressed in heterologous systems to reveal their biophysical and pharmacological functions and to determine their currents in native tissues. All mammalian EAG subfamily K+ channels that have been identified have properties typical of delayed rectifiers, with no measurable inactivation []. Only the Drosophila melanogaster Eag channel exhibits partial inactivation. |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The first EAG K+ channel was identified in Drosophila melanogaster (Fruit fly), following a screen for mutations giving rise to behavioural abnormalities. Disruption of the Eag gene caused an ether-induced, leg-shaking behaviour. Subsequent studies have revealed a conserved multi-gene family of EAG-like K+ channels, which are present in human and many other species. Based on the varying functional properties of the channels, the family has been divided into 3 subfamilies: EAG, ELK and ERG. Interestingly, Caenorhabditis elegans appears to lack the ELK type []. |
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| Protein Domain |
| Type: |
Family |
| Description: |
This entry consists of the voltage-dependent potassium channel beta subunit KCNAB and related proteins. The bacterial proteins in this entry lack apparent alpha subunit partners and predicted to function as soluble aldo/keto reductase enzymes [, ].Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3). |
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| Protein Domain |
| Type: |
Family |
| Description: |
Potassium channels are the most diverse group of the ion channel family [, ]. They are important in shaping the action potential, and in neuronal excitability and plasticity []. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups []: 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 []. 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 []. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [].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) []. 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.The KCNAB family (also known as the Kvbeta family) of voltage-dependent potassium channel beta subunits form complexes with the alpha subunits which can modify the properties of the channel. Four of these soluble beta subunits form a complex with four alpha subunit cytoplasmic (T1) regions. These subunits belong to the family of are NADPH-dependent aldo-keto reductases, and bind NADPH-cofactors in their active sites. Changes in the oxidoreductase activity appear to markedly influence the gating mode of Kv channels, since mutations to the catalytic residues in the active site lessen the inactivating activity of KCNAB []. The KCNAB family is further divided into 3 subfamilies: KCNAB1 (Kvbeta1), KCNAB2 (Kvbeta2) and KCNAB3 (Kvbeta3). |
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