KCNA1
entrez
3736
canonical
uniprot
Q09470
canonical
ensembl
ENSG00000111262
resolver
ensp
ENSP00000371985
resolver
enst
ENST00000382545
resolver
genesymbol
KCNA1
resolver
hgnc
HGNC:6218
resolver
uniprot
A6NM83
resolver
uniprot
Q3MIQ9
resolver
uniprot_entry
KCNA1_HUMAN
resolver
uniprot_sec
A6NM83
resolver
uniprot_sec
Q3MIQ9
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by 1.1 mM 4-aminopyridine (4-AP) and by 20 mM tetraethylammonium (TEA), but not by charybdotoxin (CTX) (PubMed:19912772). Inhibited by dendrotoxin (DTX) (PubMed:19307729). {ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19912772}.
uniprot
proteins
amino_acid_sequence
MTVMSGENVDEASAAPGHPQDGSYPRQADHDDHECCERVVINISGLRFETQLKTLAQFPNTLLGNPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDMFSEEIKFYELGEEAMEKFREDEGFIKEEERPLPEKEYQRQVWLLFEYPESSGPARVIAIVSVMVILISIVIFCLETLPELKDDKDFTGTVHRIDNTTVIYNSNIFTDPFFIVETLCIIWFSFELVVRFFACPSKTDFFKNIMNFIDIVAIIPYFITLGTEIAEQEGNQKGEQATSLAILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEAEEAESHFSSIPDAFWWAVVSMTTVGYGDMYPVTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEGEEQAQLLHVSSPNLASDSDLSRRSSSTMSKSEYMEIEEDMNNSIAHYRQVNIRTANCTTANQNCVNKSKLLTDV
uniprot
proteins
disease_involvement
DISEASE: Episodic ataxia 1 (EA1) [MIM:160120]: An autosomal dominant disorder characterized by brief episodes of ataxia and dysarthria. Neurological examination during and between the attacks demonstrates spontaneous, repetitive discharges in the distal musculature (myokymia) that arise from peripheral nerve. Nystagmus is absent. {ECO:0000269|PubMed:10355668, ECO:0000269|PubMed:11013453, ECO:0000269|PubMed:11026449, ECO:0000269|PubMed:12077175, ECO:0000269|PubMed:15532032, ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:7842011, ECO:0000269|PubMed:8541859, ECO:0000269|PubMed:8845167, ECO:0000269|PubMed:8871592, ECO:0000269|PubMed:9600245}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Myokymia isolated 1 (MK1) [MIM:160120]: A condition characterized by spontaneous involuntary contraction of muscle fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Isolated spontaneous muscle twitches occur in many persons and have no grave significance. {ECO:0000269|PubMed:11026449, ECO:0000269|PubMed:17136396, ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818}. 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 kidney (PubMed:19903818, PubMed:8845167). Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:17156368). 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:19912772). 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:12077175, PubMed:17156368). 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:12077175, PubMed:17156368). 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 KCNA1 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19307729, PubMed:19903818, PubMed:19912772, PubMed:19968958). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability. 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 (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) release (By similarity). Plays a role in regulating the generation of action potentials and preventing hyperexcitability in myelinated axons of the vagus nerve, and thereby contributes to the regulation of heart contraction (By similarity). Required for normal neuromuscular responses (PubMed:11026449, PubMed:17136396). Regulates the frequency of neuronal action potential firing in response to mechanical stimuli, and plays a role in the perception of pain caused by mechanical stimuli, but does not play a role in the perception of pain due to heat stimuli (By similarity). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (By similarity). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (By similarity). Plays a role in the reabsorption of Mg(2+) in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential (PubMed:19307729, PubMed:23903368). {ECO:0000250|UniProtKB:P10499, ECO:0000269|PubMed:11026449, ECO:0000269|PubMed:12077175, ECO:0000269|PubMed:15837928, ECO:0000269|PubMed:17136396, ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:19968958, ECO:0000269|PubMed:21106501, ECO:0000269|PubMed:23903368, ECO:0000269|PubMed:8845167}.
uniprot
proteins
mass_dalton
56466
uniprot
proteins
mutagenesis
MUTAGEN 35..36; /note="CC->AA: No effect on palmitoylation, no effect on current kinetics."; /evidence="ECO:0000269|PubMed:15837928"; MUTAGEN 177; /note="I->N: Slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4."; /evidence="ECO:0000269|PubMed:17156368"; MUTAGEN 243; /note="C->A: Strongly decreases palmitoylation and alters current kinetics."; /evidence="ECO:0000269|PubMed:15837928"; MUTAGEN 255; /note="N->A,H,T: Slightly increases channel activity, but does not affect expression at the cell membrane."; /evidence="ECO:0000269|PubMed:19307729"; MUTAGEN 255; /note="N->E: Abolishes channel activity, but does not affect expression at the cell membrane."; /evidence="ECO:0000269|PubMed:19307729"; MUTAGEN 255; /note="N->Q: Strongly reduces channel activity, but does not affect expression at the cell membrane."; /evidence="ECO:0000269|PubMed:19307729"; MUTAGEN 255; /note="N->V: No effect on channel activity."; /evidence="ECO:0000269|PubMed:19307729"; MUTAGEN 446; /note="S->A: Impairs phosphorylation by PKA."; /evidence="ECO:0000269|PubMed:23774215"; MUTAGEN 446; /note="S->E: Impairs expression at the cell membrane."; /evidence="ECO:0000269|PubMed:23774215
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000250|UniProtKB:P10499}.; PTM: Palmitoylated on Cys-243; which may be required for membrane targeting. {ECO:0000269|PubMed:15837928}.; PTM: Phosphorylated on tyrosine residues. Phosphorylation increases in response to NRG1; this inhibits channel activity (By similarity). Phosphorylation at Ser-446 regulates channel activity by down-regulating expression at the cell membrane (PubMed:23774215). {ECO:0000250|UniProtKB:P16388, ECO:0000269|PubMed:23774215}.
uniprot
proteins
protein_family
A (Shaker) (TC 1.A.1.2) subfamily
uniprot
proteins
protein_family
Kv1.1/KCNA1 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10355668
uniprot
proteins
pubmed
11013453
uniprot
proteins
pubmed
11026449
uniprot
proteins
pubmed
11086297
uniprot
proteins
pubmed
12077175
uniprot
proteins
pubmed
12907802
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15532032
uniprot
proteins
pubmed
15837928
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17136396
uniprot
proteins
pubmed
17156368
uniprot
proteins
pubmed
17917103
uniprot
proteins
pubmed
19307729
uniprot
proteins
pubmed
19903818
uniprot
proteins
pubmed
19912772
uniprot
proteins
pubmed
19968958
uniprot
proteins
pubmed
21106501
uniprot
proteins
pubmed
2128063
uniprot
proteins
pubmed
21483673
uniprot
proteins
pubmed
23774215
uniprot
proteins
pubmed
23903368
uniprot
proteins
pubmed
27864847
uniprot
proteins
pubmed
7842011
uniprot
proteins
pubmed
8541859
uniprot
proteins
pubmed
8845167
uniprot
proteins
pubmed
8871592
uniprot
proteins
pubmed
9600245
uniprot
proteins
sequence_length
495
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12077175, ECO:0000269|PubMed:15837928, ECO:0000269|PubMed:17136396, ECO:0000269|PubMed:17156368, ECO:0000269|PubMed:19307729, ECO:0000269|PubMed:19903818, ECO:0000269|PubMed:19912772, ECO:0000269|PubMed:19968958, ECO:0000269|PubMed:23903368}; Multi-pass membrane protein {ECO:0000305}. Membrane {ECO:0000269|PubMed:11086297}. Cell projection, axon {ECO:0000269|PubMed:11086297}. Cytoplasmic vesicle {ECO:0000269|PubMed:23774215}. Perikaryon {ECO:0000250|UniProtKB:P10499}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P10499}. Cell projection, dendrite {ECO:0000250|UniProtKB:P16388}. Cell junction {ECO:0000250|UniProtKB:P16388}. Synapse {ECO:0000250|UniProtKB:P16388}. Presynaptic cell membrane {ECO:0000250|UniProtKB:P10499}. Presynapse {ECO:0000250|UniProtKB:P16388}. Note=Homotetrameric KCNA1 is primarily located in the endoplasmic reticulum. Interaction with KCNA2 and KCNAB2 or with KCNA4 and KCNAB2 promotes expression at the cell membrane (By similarity). {ECO:0000250|UniProtKB:P10499, ECO:0000250|UniProtKB:P16388}.
uniprot
proteins
transmembrane_region
TRANSMEM 165..186; /note="Helical; Name=Segment S1"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 221..242; /note="Helical; Name=Segment S2"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 254..274; /note="Helical; Name=Segment S3"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 288..308; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 324..345; /note="Helical; Name=Segment S5"; /evidence="ECO:0000250|UniProtKB:P63142"; TRANSMEM 387..415; /note="Helical; Name=Segment S6"; /evidence="ECO:0000250|UniProtKB:P63142
uniprot
proteins