UniProt functional annotation for P63142



	UniProt functional annotation for P63142

UniProt code: P63142.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

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 (PubMed:12151401, PubMed:21602278, PubMed:24472174). 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 (PubMed:8495559, PubMed:15618540, PubMed:20805574, PubMed:23725331). 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 (PubMed:18003609, PubMed:19713757). 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 (PubMed:1715584, PubMed:16770729, PubMed:17766348, PubMed:18003609, PubMed:18638484, PubMed:19713757, PubMed:20089912). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). 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 (PubMed:23318870). KCNA2- containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:12777451). 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 (PubMed:16210348). 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 (PubMed:16306173). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (PubMed:17869444). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21647367). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (PubMed:24472174). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity). {ECO:0000250|UniProtKB:P63141, ECO:0000269|PubMed:11007484, ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:12777451, ECO:0000269|PubMed:15618540, ECO:0000269|PubMed:16210348, ECO:0000269|PubMed:16770729, ECO:0000269|PubMed:1715584, ECO:0000269|PubMed:17766348, ECO:0000269|PubMed:18003609, ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:18638484, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20805574, ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:23318870, ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2555158, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8495559, ECO:0000305, ECO:0000305|PubMed:12177193, ECO:0000305|PubMed:16306173, ECO:0000305|PubMed:17869444, ECO:0000305|PubMed:21647367}.

Activity regulation: Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:2555158, PubMed:8495559, PubMed:18638484). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (PubMed:8355670). Inhibited by maurotoxin (PubMed:24472174). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity). {ECO:0000250|UniProtKB:P16389, ECO:0000269|PubMed:18638484, ECO:0000269|PubMed:20805574, ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2555158, ECO:0000269|PubMed:8355670, ECO:0000269|PubMed:8495559}.

Biophysicochemical properties: Kinetic parameters: Note=Homotetrameric channels activate rapidly, i.e within a few msec, but inactivation is very slow, with only a marginal decrease in conductance over several seconds. The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, post-translational modifications and the presence or absence of ancillary subunits. For the activation of homotetrameric channels expressed in xenopus oocytes, the voltage at half-maximal amplitude is about -34 mV (PubMed:2555158). Unit channel conductance is about 10 pS (PubMed:2555158). For the activation of homotetrameric channels expressed in Chinese hamster ovary (CHO) cells, the voltage at half- maximal amplitude is about -10 mV (PubMed:17324383). {ECO:0000269|PubMed:17324383, ECO:0000269|PubMed:2555158};

Subunit: Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8495559, PubMed:8361540, PubMed:10896669, PubMed:12777451, PubMed:12632190, PubMed:15618540, PubMed:11007484, PubMed:16002581, PubMed:18004376, PubMed:20534430). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (PubMed:18003609, PubMed:19713757, PubMed:16002581, PubMed:18004376, PubMed:20534430, PubMed:20360102, PubMed:23705070). Identified in a complex with KCNA1 and KCNAB2 (PubMed:11086297, PubMed:23318870). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1 and DLG2 (PubMed:7477295). Interacts with DLG4 (via PDZ domain) (PubMed:7477295, PubMed:20089912). Interacts with PTK2B (PubMed:11739373). Interacts (via C-terminus) with CTTN (PubMed:12151401). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (PubMed:9635436). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with CNTNAP2 (PubMed:10624965). Interacts with ADAM22 (PubMed:20089912). {ECO:0000250|UniProtKB:P63141, ECO:0000250|UniProtKB:Q09081, ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:11007484, ECO:0000269|PubMed:11086297, ECO:0000269|PubMed:11739373, ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:12632190, ECO:0000269|PubMed:15618540, ECO:0000269|PubMed:16002581, ECO:0000269|PubMed:18004376, ECO:0000269|PubMed:19713757, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:20360102, ECO:0000269|PubMed:20534430, ECO:0000269|PubMed:23318870, ECO:0000269|PubMed:23705070, ECO:0000269|PubMed:7477295, ECO:0000269|PubMed:8361540, ECO:0000269|PubMed:8495559, ECO:0000269|PubMed:9635436, ECO:0000305}.

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}. Cell junction, synapse {ECO:0000269|PubMed:8361540}. Cell junction, synapse, synaptosome {ECO:0000250|UniProtKB:P63141}. Cell junction, synapse, 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}.

Tissue specificity: Detected in neurons in dorsal root ganglion (PubMed:24472174). Detected in hippocampus neurons (PubMed:21602278). Detected on neurons of the anteroventral cochlear nucleus (PubMed:12777451). Detected in renal arteries (PubMed:12632190). Detected in neurons of the medial nucleus of the trapezoid body (PubMed:12177193). Detected in neurons in the brain cortex (PubMed:14713306). Detected in axon tracts of the corpus callosum, specific terminal fields of the brain cortex neuropil, neurons in the medial entorhinal cortex, and in puncta representing mossy fiber terminals in the hippocampus mossy fiber tract; these puncta correspond to synapses made by dentate granule cells (PubMed:8361540). Detected in paranodal and juxtanodal zones in the central nervous system, including myelinated spinal cord (PubMed:11086297, PubMed:20089912). Detected in the juxtaparanodal region in optic nerve (PubMed:10624965). Detected at nerve terminal plexuses of basket cells in the cerebellum (at protein level) (PubMed:7477295, PubMed:20089912). Detected in brain (PubMed:2722779). Detected in heart atrium and ventricle (PubMed:1715584). Detected in renal arteries (PubMed:12632190). {ECO:0000269|PubMed:10624965, ECO:0000269|PubMed:11086297, ECO:0000269|PubMed:12177193, ECO:0000269|PubMed:12632190, ECO:0000269|PubMed:14713306, ECO:0000269|PubMed:1715584, ECO:0000269|PubMed:20089912, ECO:0000269|PubMed:21602278, ECO:0000269|PubMed:24472174, ECO:0000269|PubMed:2722779, ECO:0000269|PubMed:7477295, ECO:0000269|PubMed:8361540}.

Induction: Up-regulated in brain cortex in response to ischemia (at protein level) (PubMed:14713306). Down-regulated in dorsal root ganglion neurons after peripheral nerve injury (at protein level) (PubMed:24472174). Down-regulated in pulmonary artery myocytes in response to chronic moderate hypoxia. {ECO:0000269|PubMed:14713306, ECO:0000269|PubMed:15151918, ECO:0000269|PubMed:24472174}.

Domain: The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (PubMed:11007484). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA- mediated endocytosis (PubMed:9635436). {ECO:0000269|PubMed:11007484, ECO:0000269|PubMed:19403695, ECO:0000269|PubMed:9635436}.

Domain: The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. {ECO:0000305|PubMed:16002579, ECO:0000305|PubMed:20360102}.

Ptm: Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (PubMed:14713306). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (PubMed:7544443). Phosphorylation on tyrosine residues suppresses ion channel activity (PubMed:7544443). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN (PubMed:12151401). This is probably due to endocytosis of the phosphorylated channel subunits. Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (PubMed:18003609). {ECO:0000269|PubMed:12151401, ECO:0000269|PubMed:14713306, ECO:0000269|PubMed:18003609, ECO:0000269|PubMed:7544443}.

Ptm: N-glycosylated, with complex, sialylated N-glycans. {ECO:0000269|PubMed:10896669, ECO:0000269|PubMed:16770729}.

Miscellaneous: The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP). {ECO:0000305|PubMed:17917103}.

Similarity: Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



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 (PubMed:12151401, PubMed:21602278, PubMed:24472174). 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 (PubMed:8495559, PubMed:15618540, PubMed:20805574, PubMed:23725331). 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 (PubMed:18003609, PubMed:19713757). 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 (PubMed:1715584, PubMed:16770729, PubMed:17766348, PubMed:18003609, PubMed:18638484, PubMed:19713757, PubMed:20089912). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). 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 (PubMed:23318870). KCNA2- containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (PubMed:12777451). 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 (PubMed:16210348). 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 (PubMed:16306173). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (PubMed:17869444). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21647367). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (PubMed:24472174). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity). {ECO:0000250\|UniProtKB:P63141, ECO:0000269\|PubMed:11007484, ECO:0000269\|PubMed:12151401, ECO:0000269\|PubMed:12177193, ECO:0000269\|PubMed:12777451, ECO:0000269\|PubMed:15618540, ECO:0000269\|PubMed:16210348, ECO:0000269\|PubMed:16770729, ECO:0000269\|PubMed:1715584, ECO:0000269\|PubMed:17766348, ECO:0000269\|PubMed:18003609, ECO:0000269\|PubMed:18004376, ECO:0000269\|PubMed:18638484, ECO:0000269\|PubMed:20089912, ECO:0000269\|PubMed:20805574, ECO:0000269\|PubMed:21602278, ECO:0000269\|PubMed:23318870, ECO:0000269\|PubMed:24472174, ECO:0000269\|PubMed:2555158, ECO:0000269\|PubMed:7544443, ECO:0000269\|PubMed:8495559, ECO:0000305, ECO:0000305\|PubMed:12177193, ECO:0000305\|PubMed:16306173, ECO:0000305\|PubMed:17869444, ECO:0000305\|PubMed:21647367}.


Activity regulation:		Inhibited by 4-aminopyridine (4-AP), dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:2555158, PubMed:8495559, PubMed:18638484). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (PubMed:8355670). Inhibited by maurotoxin (PubMed:24472174). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity). {ECO:0000250\|UniProtKB:P16389, ECO:0000269\|PubMed:18638484, ECO:0000269\|PubMed:20805574, ECO:0000269\|PubMed:24472174, ECO:0000269\|PubMed:2555158, ECO:0000269\|PubMed:8355670, ECO:0000269\|PubMed:8495559}.
Biophysicochemical properties:		Kinetic parameters: Note=Homotetrameric channels activate rapidly, i.e within a few msec, but inactivation is very slow, with only a marginal decrease in conductance over several seconds. The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, post-translational modifications and the presence or absence of ancillary subunits. For the activation of homotetrameric channels expressed in xenopus oocytes, the voltage at half-maximal amplitude is about -34 mV (PubMed:2555158). Unit channel conductance is about 10 pS (PubMed:2555158). For the activation of homotetrameric channels expressed in Chinese hamster ovary (CHO) cells, the voltage at half- maximal amplitude is about -10 mV (PubMed:17324383). {ECO:0000269\|PubMed:17324383, ECO:0000269\|PubMed:2555158};
Subunit:		Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:8495559, PubMed:8361540, PubMed:10896669, PubMed:12777451, PubMed:12632190, PubMed:15618540, PubMed:11007484, PubMed:16002581, PubMed:18004376, PubMed:20534430). Channel activity is regulated by interaction with beta subunits, including KCNAB1 and KCNAB2 (PubMed:18003609, PubMed:19713757, PubMed:16002581, PubMed:18004376, PubMed:20534430, PubMed:20360102, PubMed:23705070). Identified in a complex with KCNA1 and KCNAB2 (PubMed:11086297, PubMed:23318870). Identified in a complex with KCNA5 and KCNAB1 (By similarity). Identified in a complex with KCNA4 and FYN (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1 and DLG2 (PubMed:7477295). Interacts with DLG4 (via PDZ domain) (PubMed:7477295, PubMed:20089912). Interacts with PTK2B (PubMed:11739373). Interacts (via C-terminus) with CTTN (PubMed:12151401). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (PubMed:9635436). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with CNTNAP2 (PubMed:10624965). Interacts with ADAM22 (PubMed:20089912). {ECO:0000250\|UniProtKB:P63141, ECO:0000250\|UniProtKB:Q09081, ECO:0000269\|PubMed:10624965, ECO:0000269\|PubMed:10896669, ECO:0000269\|PubMed:11007484, ECO:0000269\|PubMed:11086297, ECO:0000269\|PubMed:11739373, ECO:0000269\|PubMed:12151401, ECO:0000269\|PubMed:12632190, ECO:0000269\|PubMed:15618540, ECO:0000269\|PubMed:16002581, ECO:0000269\|PubMed:18004376, ECO:0000269\|PubMed:19713757, ECO:0000269\|PubMed:20089912, ECO:0000269\|PubMed:20360102, ECO:0000269\|PubMed:20534430, ECO:0000269\|PubMed:23318870, ECO:0000269\|PubMed:23705070, ECO:0000269\|PubMed:7477295, ECO:0000269\|PubMed:8361540, ECO:0000269\|PubMed:8495559, ECO:0000269\|PubMed:9635436, ECO:0000305}.
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}. Cell junction, synapse {ECO:0000269\|PubMed:8361540}. Cell junction, synapse, synaptosome {ECO:0000250\|UniProtKB:P63141}. Cell junction, synapse, 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}.
Tissue specificity:		Detected in neurons in dorsal root ganglion (PubMed:24472174). Detected in hippocampus neurons (PubMed:21602278). Detected on neurons of the anteroventral cochlear nucleus (PubMed:12777451). Detected in renal arteries (PubMed:12632190). Detected in neurons of the medial nucleus of the trapezoid body (PubMed:12177193). Detected in neurons in the brain cortex (PubMed:14713306). Detected in axon tracts of the corpus callosum, specific terminal fields of the brain cortex neuropil, neurons in the medial entorhinal cortex, and in puncta representing mossy fiber terminals in the hippocampus mossy fiber tract; these puncta correspond to synapses made by dentate granule cells (PubMed:8361540). Detected in paranodal and juxtanodal zones in the central nervous system, including myelinated spinal cord (PubMed:11086297, PubMed:20089912). Detected in the juxtaparanodal region in optic nerve (PubMed:10624965). Detected at nerve terminal plexuses of basket cells in the cerebellum (at protein level) (PubMed:7477295, PubMed:20089912). Detected in brain (PubMed:2722779). Detected in heart atrium and ventricle (PubMed:1715584). Detected in renal arteries (PubMed:12632190). {ECO:0000269\|PubMed:10624965, ECO:0000269\|PubMed:11086297, ECO:0000269\|PubMed:12177193, ECO:0000269\|PubMed:12632190, ECO:0000269\|PubMed:14713306, ECO:0000269\|PubMed:1715584, ECO:0000269\|PubMed:20089912, ECO:0000269\|PubMed:21602278, ECO:0000269\|PubMed:24472174, ECO:0000269\|PubMed:2722779, ECO:0000269\|PubMed:7477295, ECO:0000269\|PubMed:8361540}.
Induction:		Up-regulated in brain cortex in response to ischemia (at protein level) (PubMed:14713306). Down-regulated in dorsal root ganglion neurons after peripheral nerve injury (at protein level) (PubMed:24472174). Down-regulated in pulmonary artery myocytes in response to chronic moderate hypoxia. {ECO:0000269\|PubMed:14713306, ECO:0000269\|PubMed:15151918, ECO:0000269\|PubMed:24472174}.
Domain:		The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (PubMed:11007484). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA- mediated endocytosis (PubMed:9635436). {ECO:0000269\|PubMed:11007484, ECO:0000269\|PubMed:19403695, ECO:0000269\|PubMed:9635436}.
Domain:		The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region. {ECO:0000305\|PubMed:16002579, ECO:0000305\|PubMed:20360102}.
Ptm:		Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (PubMed:14713306). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (PubMed:7544443). Phosphorylation on tyrosine residues suppresses ion channel activity (PubMed:7544443). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN (PubMed:12151401). This is probably due to endocytosis of the phosphorylated channel subunits. Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (PubMed:18003609). {ECO:0000269\|PubMed:12151401, ECO:0000269\|PubMed:14713306, ECO:0000269\|PubMed:18003609, ECO:0000269\|PubMed:7544443}.
Ptm:		N-glycosylated, with complex, sialylated N-glycans. {ECO:0000269\|PubMed:10896669, ECO:0000269\|PubMed:16770729}.
Miscellaneous:		The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP). {ECO:0000305\|PubMed:17917103}.
Similarity:		Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily. {ECO:0000305}.