Protein Domain : IPR008074

Type:  Family Name:  Two pore domain potassium channel, TRAAK
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 iscomposed 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 themaintenance 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 hasbeen 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.2P-domain channels influence the resting membrane potential and as a result can control cell excitability. In addition, they pass K+ in response to changes in membrane potential, and are also tightly regulated by molecular oxygen, GABA (gamma-aminobutyric acid), noradrenaline and serotonin.The first member of this family (TOK1), cloned from Saccharomyces cerevisiae[], ispredicted to have eight potential transmembrane (TM) helices. However, subsequently-cloned two P-domain family members from Drosophila andmammalian species are predicted to have only four TM segments. They are usually referred to as TWIK-related channels (Tandem of P-domains in a Weakly Inward rectifying K+ channel) [, , , ]. Functional characterisation of these channels has revealed a diversity of properties in that they may show inward or outward rectification, their activity may be modulated in different directions by protein phosphorylation, and their sensitivity to changes in intracellular or extracellular pH varies. Despite these disparate properties, they are all thought to share the same topology offour TM segments, including two P-domains. That TWIK-related K+ channels all produce instantaneous and non-inactivating K+ currents, which do notdisplay a voltage-dependent activation threshold, suggests that they are background (leak) K+ channels involved in the generation and modulation of the resting membrane potential in various cell types. Further studies have revealed that they may be found in many species, including: plants, invertebrates and mammals.TRAAK (TWIK-related arachidonic acid-stimulated K+ channel) is a member of the 2P-domain K+ channel family, and is expressed mainly in the brain andplacenta. It is strongly activated by unsaturated fatty acids, such as oleate and linoleate. An alternative way of activating TRAAK channels is theapplication of stretch to the cell membrane, for example, by means of cell swelling, shear stress or negative pressure []. Short Name:  2pore_dom_K_chnl_TRAAK

0 Child Features

1 Contains

DB identifier Type Name
IPR013099 Domain Potassium channel domain

1 Cross References

Identifier
PR01691

0 Found In

3 GO Annotations

GO Term Gene Name
GO:0005267 IPR008074
GO:0071805 IPR008074
GO:0016020 IPR008074

3 Ontology Annotations

GO Term Gene Name
GO:0005267 IPR008074
GO:0071805 IPR008074
GO:0016020 IPR008074

1 Parent Features

DB identifier Type Name
IPR003280 Family Two pore domain potassium channel

0 Proteins

13 Publications

First Author Title Year Journal Volume Pages PubMed ID
            1772658
            1879548
            1373731
            2448635
            2451788
            2555158
            11178249
            8605869
            9003761
            9312005
            7651518
            8917578
            9880510