| Primary Identifier | IPR005402 | Type | Family |
| Short Name | K_chnl_volt-dep_bsu_KCNAB3 |
| 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. Thefunctional 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).KCNAB3 associates with Kv1.5 alpha subunits, resulting in a much faster inactivation than is observed in kv1.5 channels formed from alpha subunitsalone []. KCNAB3 channels are expressed specifically in the brain, with most prominent expression in the cerebellum. Weaker expression is observed in the cortex, occipital lobe, frontal lobe and temporal lobe. |
