KCNA2
entrez
3737
canonical
uniprot
P16389
canonical
ensembl
ENSG00000177301
resolver
ensp
ENSP00000314520
resolver
ensp
ENSP00000358785
resolver
ensp
ENSP00000487785
resolver
ensp
ENSP00000491613
resolver
ensp
ENSP00000521711
resolver
ensp
ENSP00000521712
resolver
genesymbol
KCNA2
resolver
hgnc
HGNC:6220
resolver
uniprot
A0A024R0D3
resolver
uniprot
A8K1Z6
resolver
uniprot
Q86XG6
resolver
uniprot_entry
KCNA2_HUMAN
resolver
uniprot_sec
A0A024R0D3
resolver
uniprot_sec
A8K1Z6
resolver
uniprot_sec
Q86XG6
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by 4-aminopyridine (4-AP) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (PubMed:19912772). Inhibited by dendrotoxin (DTX) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK; kappaM-RIIIJ has much higher affinity for channels containing KCNA2 than kappaM-RIIIK, with the exception of heterodimers formed by KCNA2 and KCNA7 where the opposite is true (PubMed:20220134). {ECO:0000250|UniProtKB:P63141, ECO:0000250|UniProtKB:P63142, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:20220134}.
uniprot
proteins
amino_acid_sequence
MTVATGDPADEAAALPGHPQDTYDPEADHECCERVVINISGLRFETQLKTLAQFPETLLGDPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFSEEIRFYELGEEAMEMFREDEGYIKEEERPLPENEFQRQVWLLFEYPESSGPARIIAIVSVMVILISIVSFCLETLPIFRDENEDMHGSGVTFHTYSNSTIGYQQSTSFTDPFFIVETLCIIWFSFEFLVRFFACPSKAGFFTNIMNIIDIVAIIPYFITLGTELAEKPEDAQQGQQAMSLAILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEADERESQFPSIPDAFWWAVVSMTTVGYGDMVPTTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEGEEQAQYLQVTSCPKIPSSPDLKKSRSASTISKSDYMEIQEGVNNSNEDFREENLKTANCTLANTNYVNITKMLTDV
uniprot
proteins
disease_involvement
DISEASE: Developmental and epileptic encephalopathy 32 (DEE32) [MIM:616366]: A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE32 inheritance is autosomal dominant. {ECO:0000269|PubMed:25477152, ECO:0000269|PubMed:25751627, ECO:0000269|PubMed:32833227, ECO:0000269|PubMed:34576077, ECO:0000269|PubMed:35439054, ECO:0000269|PubMed:37883018}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Nizon-Isidor syndrome (NIZIDS) [MIM:618872]: An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, global developmental delay, speech impairment, and behavioral abnormalities including autism spectrum disorder and aggressive behavior. Other features include a thin corpus callosum, and mild facial dysmorphism. Disease onset is in infancy or early childhood. {ECO:0000269|PubMed:37883018}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
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:11211111, PubMed:19912772, PubMed:23769686, PubMed:8495559). 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:20220134, PubMed:8495559). 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 (PubMed:19912772, PubMed:23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). 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). {ECO:0000250|UniProtKB:P63141, ECO:0000250|UniProtKB:P63142, 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, ECO:0000305}.
uniprot
proteins
mass_dalton
56717
uniprot
proteins
mutagenesis
MUTAGEN 381; /note="V->R: Abolishes pore blocking and subsequent channel inhibition by the Pterinochilus murinus spider venom toxin Murinotoxin-1."; /evidence="ECO:0000269|PubMed:40778948
uniprot
proteins
post_translational_modification
PTM: Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (By similarity). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (By similarity). Phosphorylation on tyrosine residues suppresses ion channel activity (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN. This is probably due to endocytosis of the phosphorylated channel subunits (By similarity). Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (By similarity). {ECO:0000250|UniProtKB:P63142}.; PTM: N-glycosylated, with complex, sialylated N-glycans. {ECO:0000250|UniProtKB:P63142}.
uniprot
proteins
protein_family
A (Shaker) (TC 1.A.1.2) subfamily
uniprot
proteins
protein_family
Kv1.2/KCNA2 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10624965
uniprot
proteins
pubmed
11086297
uniprot
proteins
pubmed
11211111
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16473933
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17917103
uniprot
proteins
pubmed
19713757
uniprot
proteins
pubmed
19912772
uniprot
proteins
pubmed
20220134
uniprot
proteins
pubmed
22649228
uniprot
proteins
pubmed
23769686
uniprot
proteins
pubmed
24613312
uniprot
proteins
pubmed
25477152
uniprot
proteins
pubmed
25751627
uniprot
proteins
pubmed
27864847
uniprot
proteins
pubmed
32833227
uniprot
proteins
pubmed
34576077
uniprot
proteins
pubmed
35439054
uniprot
proteins
pubmed
37883018
uniprot
proteins
pubmed
40778948
uniprot
proteins
pubmed
8495559
uniprot
proteins
sequence_length
499
uniprot
proteins
subcellular_location
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}.
uniprot
proteins
transmembrane_region
TRANSMEM 161..182; /note="Helical; Name=Segment S1"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 222..243; /note="Helical; Name=Segment S2"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 255..275; /note="Helical; Name=Segment S3"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 290..310; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 326..347; /note="Helical; Name=Segment S5"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 389..417; /note="Helical; Name=Segment S6"; /evidence="ECO:0000250|UniProtKB:P63142
uniprot
proteins