Protein: Potassium voltage-gated channel subfamily A member 2 (NGK1) (Voltage-gated K(+) channel HuKIV) (Voltage-gated potassium channel HBK5) (Voltage-gated potassium channel subunit Kv1.2) (P16389)
Organism: Homo sapiens (Human)
Function: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure. In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation. Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
Subcellular location: Cell membrane {ECO:0000269|PubMed:11211111, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:20220134, ECO:0000269|PubMed:23769686, ECO:0000269|PubMed:32833227, ECO:0000269|PubMed:35439054, ECO:0000269|PubMed:37883018, ECO:0000269|PubMed:8495559}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P63142, ECO:0000305}. Membrane {ECO:0000250|UniProtKB:P63142}. Cell projection, axon {ECO:0000269|PubMed:16473933}. Synapse {ECO:0000250|UniProtKB:P63142}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P63142}. Cell projection, lamellipodium membrane {ECO:0000250|UniProtKB:P63142}. Synapse, synaptosome {ECO:0000250|UniProtKB:P63141}. Presynaptic cell membrane {ECO:0000250|UniProtKB:P63141}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63141}. Cell junction, paranodal septate junction {ECO:0000250|UniProtKB:P63141}. Note=KCNA2 by itself is detected both at the endoplasmic reticulum and at the cell membrane. Coexpression with KCNA4 or with beta subunits promotes expression at the cell membrane. Coexpression with KCNA1 inhibits cell surface expression. In myelinated peripheral axons, clustered in the juxtaparadonal region and at an internodal line located along the mesaxon and below the Schmidt-Lanterman incisures (By similarity). {ECO:0000250|UniProtKB:P63141, ECO:0000250|UniProtKB:P63142}.
Sequence: MTVATGDPADEAAALPGHPQDTYDPEADHECCERVVINISGLRFETQLKTLAQFPETLLGDPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFSEEIRFYELGEEAMEMFREDEGYIKEEERPLPENEFQRQVWLLFEYPESSGPARIIAIVSVMVILISIVSFCLETLPIFRDENEDMHGSGVTFHTYSNSTIGYQQSTSFTDPFFIVETLCIIWFSFEFLVRFFACPSKAGFFTNIMNIIDIVAIIPYFITLGTELAEKPEDAQQGQQAMSLAILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEADERESQFPSIPDAFWWAVVSMTTVGYGDMVPTTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEGEEQAQYLQVTSCPKIPSSPDLKKSRSASTISKSDYMEIQEGVNNSNEDFREENLKTANCTLANTNYVNITKMLTDV
InterPro domains: - IPR003972: Potassium channel, voltage dependent, Kv1 (family) [62-187]
- IPR028325: Voltage-gated potassium channel (family) [33-445]
- IPR027359: Voltage-dependent channel domain superfamily (homologous_superfamily) [133-310]
- IPR003131: Potassium channel tetramerisation-type BTB domain (domain) [35-125]
- IPR000210: BTB/POZ domain (domain) [33-133]
- IPR011333: SKP1/BTB/POZ domain superfamily (homologous_superfamily) [32-132]
- IPR004049: Potassium channel, voltage dependent, Kv1.2 (family) [195-475]
- IPR003968: Potassium channel, voltage dependent, Kv (family) [75-409]
- IPR005821: Ion transport domain (domain) [163-420]
Interaction partners: - Voltage-gated potassium channel subunit beta-2
- Potassium voltage-gated channel subfamily A member 1
- Potassium voltage-gated channel subfamily A member 6
- Contactin-associated protein-like 2
- Potassium voltage-gated channel subfamily A member 4
- Src substrate cortactin
- Potassium voltage-gated channel subfamily A member 5
- Voltage-gated potassium channel subunit beta-1
- Potassium voltage-gated channel subfamily A member 3
- Potassium voltage-gated channel subfamily B member 1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0005515 (protein binding), GO:0015075 (monoatomic ion transmembrane transporter activity), GO:0022803 (passive transmembrane transporter activity), GO:0008092 (cytoskeletal protein binding), GO:1901702 (salt transmembrane transporter activity), GO:0015318 (inorganic molecular entity transmembrane transporter activity), GO:0015079 (potassium ion transmembrane transporter activity), GO:0015267 (channel activity), GO:0008324 (monoatomic cation transmembrane transporter activity), GO:0005216 (monoatomic ion channel activity), GO:0022890 (inorganic cation transmembrane transporter activity), GO:0019894 (kinesin binding), GO:0046873 (metal ion transmembrane transporter activity), GO:0005261 (monoatomic cation channel activity), GO:0022839 (monoatomic ion gated channel activity), GO:0005267 (potassium channel activity), GO:0022836 (gated channel activity), GO:0022843 (voltage-gated monoatomic cation channel activity), GO:0005244 (voltage-gated monoatomic ion channel activity), GO:0005249 (voltage-gated potassium channel activity), GO:0022832 (voltage-gated channel activity), GO:0005251 (delayed rectifier potassium channel activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0051179 (localization), GO:0042592 (homeostatic process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0048878 (chemical homeostasis), GO:0007267 (cell-cell signaling), GO:0065008 (regulation of biological quality), GO:0055085 (transmembrane transport), GO:0051234 (establishment of localization), GO:0003008 (system process), GO:0007154 (cell communication), GO:0050801 (monoatomic ion homeostasis), GO:0099536 (synaptic signaling), GO:0098660 (inorganic ion transmembrane transport), GO:0042391 (regulation of membrane potential), GO:0006810 (transport), GO:0098771 (inorganic ion homeostasis), GO:0050877 (nervous system process), GO:0034220 (monoatomic ion transmembrane transport), GO:0098655 (monoatomic cation transmembrane transport), GO:0050905 (neuromuscular process), GO:0098662 (inorganic cation transmembrane transport), GO:0055080 (monoatomic cation homeostasis), GO:0010960 (magnesium ion homeostasis), GO:0099537 (trans-synaptic signaling), GO:0006811 (monoatomic ion transport), GO:0071805 (potassium ion transmembrane transport), GO:0006812 (monoatomic cation transport), GO:0098916 (anterograde trans-synaptic signaling), GO:0030001 (metal ion transport), GO:0007268 (chemical synaptic transmission), GO:0006813 (potassium ion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0042995 (cell projection), GO:0016020 (membrane), GO:0033270 (paranode region of axon), GO:0044304 (main axon), GO:0071944 (cell periphery), GO:0098796 (membrane protein complex), GO:1990351 (transporter complex), GO:0098797 (plasma membrane protein complex), GO:1902495 (transmembrane transporter complex), GO:0120025 (plasma membrane bounded cell projection), GO:0005886 (plasma membrane), GO:0043005 (neuron projection), GO:0034702 (ion channel complex), GO:0008076 (voltage-gated potassium channel complex), GO:0034703 (cation channel complex), GO:0030424 (axon), GO:0034705 (potassium channel complex)