Two pore domain potassium channel, THIK (IPR005410)
Short name: 2pore_dom_K_chnl_THIK
- Two pore domain potassium channel (IPR003280)
- Two pore domain potassium channel, THIK (IPR005410)
Potassium channels are the most diverse group of the ion channel family [PMID: 1772658, PMID: 1879548]. They are important in shaping the action potential, and in neuronal excitability and plasticity [PMID: 2451788]. The potassium channel family is composed of several functionally distinct isoforms, which can be broadly separated into 2 groups [PMID: 2555158]: the practically non-inactivating 'delayed' group and the rapidly inactivating 'transient' group.
These are all highly similar proteins, with only small amino acid changes causing the diversity of the voltage-dependent gating mechanism, channel conductance and toxin binding properties. Each type of K+ channel is activated by different signals and conditions depending on their type of regulation: some open in response to depolarisation of the plasma membrane; others in response to hyperpolarisation or an increase in intracellular calcium concentration; some can be regulated by binding of a transmitter, together with intracellular kinases; while others are regulated by GTP-binding proteins or other second messengers [PMID: 2448635]. In eukaryotic cells, K+ channels are involved in neural signalling and generation of the cardiac rhythm, act as effectors in signal transduction pathways involving G protein-coupled receptors (GPCRs) and may have a role in target cell lysis by cytotoxic T-lymphocytes [PMID: 1373731]. In prokaryotic cells, they play a role in the maintenance of ionic homeostasis [PMID: 11178249].
All K+ channels discovered so far possess a core of alpha subunits, each comprising either one or two copies of a highly conserved pore loop domain (P-domain). The P-domain contains the sequence (T/SxxTxGxG), which has been termed the K+ selectivity sequence. In families that contain one P-domain, four subunits assemble to form a selective pathway for K+ across the membrane. However, it remains unclear how the 2 P-domain subunits assemble to form a selective pore. The functional diversity of these families can arise through homo- or hetero-associations of alpha subunits or association with auxiliary cytoplasmic beta subunits. K+ channel subunits containing one pore domain can be assigned into one of two superfamilies: those that possess six transmembrane (TM) domains and those that possess only two TM domains. The six TM domain superfamily can be further subdivided into conserved gene families: the voltage-gated (Kv) channels; the KCNQ channels (originally known as KvLQT channels); the EAG-like K+ channels; and three types of calcium (Ca)-activated K+ channels (BK, IK and SK) [PMID: 11178249]. The 2TM domain family comprises inward-rectifying K+ channels. In addition, there are K+ channel alpha-subunits that possess two P-domains. These are usually highly regulated K+ selective leak channels.
The THIK (Tandem pore-domain Halothane Inhibited K+ channel) family contains two members: THIK-1 and THIK-2. Both proteins were first isolated from rat and have subsequently been found in human. THIK-1 is expressed ubiquitously and is activated by arachidonic acid and inhibited by the volatile anaesthetic halothane. The second member, THIK-2, shares 58% amino acid identity with THIK-1, but is not functionally expressed. THIK-2 is strongly expressed in several tissues, and is particularly abundant in the brain [PMID: 11060316].
- PR01588 (THIKCHANNEL)