G3DSA:2.60.40.1400

G protein-activated inward rectifier potassium channel 1

CATH-Gene3D entry
Member databaseCATH-Gene3D
CATH-Gene3D typehomologous superfamily

Description
Imported from IPR013518

Potassium channels are the most diverse group of the ion channel family
[10, 7]
. They are important in shaping the action potential, and in neuronal excitability and plasticity
[9]
. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups
[1]
: 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
[3]
. 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
[2]
. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis
[6]
.

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)
[6]
. 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
[5]
. 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
[4, 8]
.

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
[5]
.

References
Imported from IPR013518

1.Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. Stuhmer W, Ruppersberg JP, Schroter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, Pongs O. EMBO J. 8, 3235-44, (1989). View articlePMID: 2555158

2.Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes. Attali B, Romey G, Honore E, Schmid-Alliana A, Mattei MG, Lesage F, Ricard P, Barhanin J, Lazdunski M. J. Biol. Chem. 267, 8650-7, (1992). View articlePMID: 1373731

3.Multiple potassium-channel components are produced by alternative splicing at the Shaker locus in Drosophila. Schwarz TL, Tempel BL, Papazian DM, Jan YN, Jan LY. Nature 331, 137-42, (1988). View articlePMID: 2448635

4.The inward rectifier potassium channel family. Doupnik CA, Davidson N, Lester HA. Curr. Opin. Neurobiol. 5, 268-77, (1995). View articlePMID: 7580148

5.Transmembrane structure of an inwardly rectifying potassium channel. Minor DL Jr, Masseling SJ, Jan YN, Jan LY. Cell 96, 879-91, (1999). View articlePMID: 10102275

6.An overview of the potassium channel family. Miller C. Genome Biol. 1, REVIEWS0004, (2000). View articlePMID: 11178249

7.Shaw-like rat brain potassium channel cDNA's with divergent 3' ends. Luneau C, Wiedmann R, Smith JS, Williams JB. FEBS Lett. 288, 163-7, (1991). View articlePMID: 1879548

8.Inwardly rectifying potassium channels. Reimann F, Ashcroft FM. Curr. Opin. Cell Biol. 11, 503-8, (1999). View articlePMID: 10449331

9.Cloning of a probable potassium channel gene from mouse brain. Tempel BL, Jan YN, Jan LY. Nature 332, 837-9, (1988). View articlePMID: 2451788

10.The molecular biology of K+ channels. Perney TM, Kaczmarek LK. Curr. Opin. Cell Biol. 3, 663-70, (1991). View articlePMID: 1772658

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