Protein: Potassium voltage-gated channel subfamily A member 2 (RAK) (RBK2) (RCK5) (Voltage-gated potassium channel subunit Kv1.2) (P63142)
Organism: Rattus norvegicus (Rat)
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 a 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. Response to toxins that are selective for KCNA1, respectively for KCNA2, suggests that heteromeric potassium channels composed of both KCNA1 and KCNA2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neurons. KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing. 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. 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. May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA). Contributes to the regulation of the axonal release of the neurotransmitter dopamine. Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain. 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:10896669, ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:14713306, ECO:0000269|PubMed:15618540, ECO:0000269|PubMed:16770729, ECO:0000269|PubMed:1715584, ECO:0000269|PubMed:17766348, ECO:0000269|PubMed:18003609, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20805574, ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:23318870, ECO:0000269|PubMed:23725331, ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2555158, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:9635436, ECO:0000305|PubMed:11086297}; Multi-pass membrane protein {ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:16002581, ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430, ECO:0000269|PubMed:23705070, ECO:0000305}. Membrane {ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:16002581, ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:18638484, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430, ECO:0000269|PubMed:23705070, ECO:0000269|PubMed:8361540}. Cell projection, axon {ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:12777451, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:8361540}. Synapse {ECO:0000269|PubMed:8361540}. Synapse, synaptosome {ECO:0000250|UniProtKB:P63141}. Presynaptic cell membrane {ECO:0000250|UniProtKB:P63141}. Cell projection, dendrite {ECO:0000250|UniProtKB:P63141}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:10896669}. Cell projection, lamellipodium membrane {ECO:0000269|PubMed:12151401}. Endosome {ECO:0000269|PubMed:19403695}. Perikaryon {ECO:0000269|PubMed:23318870}. 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 (PubMed:10896669, PubMed:16770729, PubMed:18003609). Coexpression with KCNA1 inhibits cell surface expression (PubMed:10896669). Surface levels are regulated both by steady-state and stimulus-induced clathrin-dependent endocytosis (PubMed:19403695). Expression at the cell surface is down-regulated in response to CHRM1 activation (PubMed:9635436). Expression at the cell surface is increased in response to the activation of beta-adrenergic receptors and increased cAMP levels (PubMed:18003609). Detected on presynaptic and postsynaptic axon segments (PubMed:12777451). 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:0000269|PubMed:10896669, ECO:0000269|PubMed:12777451, ECO:0000269|PubMed:16770729, ECO:0000269|PubMed:18003609, ECO:0000269|PubMed:19403695, ECO:0000269|PubMed:9635436}.
Interaction partners:
- Voltage-gated potassium channel subunit beta-2
- Voltage-gated potassium channel subunit beta-1
- Potassium voltage-gated channel subfamily A member 1
- Potassium voltage-gated channel subfamily A member 6
- Potassium voltage-gated channel subfamily A member 4
- Voltage-gated potassium channel subunit beta-3
- Potassium voltage-gated channel subfamily A member 5
- Potassium voltage-gated channel subfamily A member 3
- Contactin-2
- FAU ubiquitin like and ribosomal protein S30 fusion like 2
Sequence:
MTVATGDPVDEAAALPGHPQDTYDPEADHECCERVVINISGLRFETQLKTLAQFPETLLGDPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFSEEIRFYELGEEAMEMFREDEGYIKEEERPLPENEFQRQVWLLFEYPESSGPARIIAIVSVMVILISIVSFCLETLPIFRDENEDMHGGGVTFHTYSNSTIGYQQSTSFTDPFFIVETLCIIWFSFEFLVRFFACPSKAGFFTNIMNIIDIVAIIPYFITLGTELAEKPEDAQQGQQAMSLAILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEADERDSQFPSIPDAFWWAVVSMTTVGYGDMVPTTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEGEEQAQYLQVTSCPKIPSSPDLKKSRSASTISKSDYMEIQEGVNNSNEDFREENLKTANCTLANTNYVNITKMLTDV