Kcna1
entrez
16485
canonical
uniprot
P16388
canonical
ensembl
ENSMUSG00000047976
resolver
ensp
ENSMUSP00000055225
resolver
ensp
ENSMUSP00000144947
resolver
enst
ENSMUST00000055168
resolver
enst
ENSMUST00000203094
resolver
genesymbol
Kcna1
resolver
uniprot_entry
KCNA1_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by 4-aminopyridine (4-AP), tetraethylammonium (TEA) and dendrotoxin (DTX), but not by charybdotoxin (CTX). {ECO:0000269|PubMed:7517498}.
uniprot
proteins
amino_acid_sequence
MTVMSGENADEASTAPGHPQDGSYPRQADHDDHECCERVVINISGLRFETQLKTLAQFPNTLLGNPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDMFSEEIKFYELGEEAMEKFREDEGFIKEEERPLPEKEYQRQVWLLFEYPESSGPARVIAIVSVMVILISIVIFCLETLPELKDDKDFTGTIHRIDNTTVIYTSNIFTDPFFIVETLCIIWFSFELVVRFFACPSKTDFFKNIMNFIDIVAIIPYFITLGTEIAEQEGNQKGEQATSLAILRVIRLVRVFRIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEAEEAESHFSSIPDAFWWAVVSMTTVGYGDMYPVTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEGEEQAQLLHVSSPNLASDSDLSRRSSSTISKSEYMEIEEDMNNSIAHYRQANIRTGNCTTADQNCVNKSKLLTDV
uniprot
proteins
disease_involvement
DISEASE: Note=A spontaneous mutation leading to a frameshift and truncation of Kcna2 causes megencephaly with a 25% increase of brain weight relative to wild-type. Especially the hippocampus shows increased proliferation of neurons and astrocytes, leading to increased brain volume (PubMed:17315199). Mutant mice appear normal at birth. After 3-4 weeks, they display low body weight, a subtle shakiness in their gait, a preference for a strange sitting position that is maintained for periods ranging from 30 seconds to several minutes, excessive lacrimation and acoustic startle hypersensitivity (PubMed:21966978, PubMed:8995755). The increase in the acoustic startle response is down-regulated by treatment with the anti-epileptic drug valproate (PubMed:21966978). Mutant mice display an abnormal electro-encephalogram with single spikes and waves, when anesthesized (PubMed:21966978). The electric activity of mossy cells from the dentate hilus region is altered and shows increased firing of action potentials, probably due to the absence of functional Kcna1 channels (PubMed:14686897). Heterozygotes show mechanical allodynia, but no increased sensitivity to heat (PubMed:23473320). Homozygotes show no alteration of the islet of Langerhans structure, of the basal levels of insulin secretion and blood glucose levels (PubMed:21483673). Compared to wild-type, they display moderately increased insulin secretion in response to a glucose stimulus (PubMed:21483673). Besides, the frequency of beta cell action potentials is increased (PubMed:21483673). {ECO:0000269|PubMed:14686897, ECO:0000269|PubMed:17315199, ECO:0000269|PubMed:21483673, ECO:0000269|PubMed:21966978, ECO:0000269|PubMed:8995755}.
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. Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability (PubMed:10191303, PubMed:12611922, PubMed:21966978, PubMed:22158511, PubMed:23473320, PubMed:9581771, PubMed:9736643). 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:15361858). 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 (PubMed:15361858). 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:15361858, PubMed:7517498). In contrast, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons, preventing neuronal hyperexcitability (PubMed:23466697). 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 (PubMed:20392939, PubMed:22641786, PubMed:25377007). Required for normal neuromuscular responses (PubMed:9736643). 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 (PubMed:23473320). Required for normal responses to auditory stimuli and precise location of sound sources, but not for sound perception (PubMed:21966978, PubMed:22396426). The use of toxins that block specific channels suggest that it contributes to the regulation of the axonal release of the neurotransmitter dopamine (PubMed:21233214). Required for normal postnatal brain development and normal proliferation of neuronal precursor cells in the brain (PubMed:17250763, PubMed:17315199, PubMed:22411008, PubMed:8995755). 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 (By similarity). {ECO:0000250|UniProtKB:P10499, ECO:0000250|UniProtKB:Q09470, ECO:0000269|PubMed:10191303, ECO:0000269|PubMed:12611922, ECO:0000269|PubMed:15361858, ECO:0000269|PubMed:17250763, ECO:0000269|PubMed:17315199, ECO:0000269|PubMed:20392939, ECO:0000269|PubMed:21233214, ECO:0000269|PubMed:21966978, ECO:0000269|PubMed:22158511, ECO:0000269|PubMed:22396426, ECO:0000269|PubMed:22411008, ECO:0000269|PubMed:22641786, ECO:0000269|PubMed:23466697, ECO:0000269|PubMed:23473320, ECO:0000269|PubMed:25377007, ECO:0000269|PubMed:7517498, ECO:0000269|PubMed:8995755, ECO:0000269|PubMed:9581771, ECO:0000269|PubMed:9736643}.
uniprot
proteins
mass_dalton
56409
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:0000250|UniProtKB:Q09470}.; PTM: Phosphorylated on tyrosine residues. Phosphorylation increases in response to NRG1; this inhibits channel activity (PubMed:22158511). Phosphorylation at Ser-446 regulates channel activity by down-regulating expression at the cell membrane (By similarity). {ECO:0000250|UniProtKB:Q09470, ECO:0000269|PubMed:22158511}.
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
10191303
uniprot
proteins
pubmed
12611922
uniprot
proteins
pubmed
12907802
uniprot
proteins
pubmed
14686897
uniprot
proteins
pubmed
15361858
uniprot
proteins
pubmed
16452087
uniprot
proteins
pubmed
17250763
uniprot
proteins
pubmed
17315199
uniprot
proteins
pubmed
17917103
uniprot
proteins
pubmed
19307729
uniprot
proteins
pubmed
20392939
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21233214
uniprot
proteins
pubmed
21483673
uniprot
proteins
pubmed
21966978
uniprot
proteins
pubmed
22158511
uniprot
proteins
pubmed
22396426
uniprot
proteins
pubmed
22411008
uniprot
proteins
pubmed
22641786
uniprot
proteins
pubmed
2305265
uniprot
proteins
pubmed
23466697
uniprot
proteins
pubmed
23473320
uniprot
proteins
pubmed
23903368
uniprot
proteins
pubmed
2451788
uniprot
proteins
pubmed
25377007
uniprot
proteins
pubmed
26269648
uniprot
proteins
pubmed
7517498
uniprot
proteins
pubmed
8046438
uniprot
proteins
pubmed
8361541
uniprot
proteins
pubmed
8995755
uniprot
proteins
pubmed
9581771
uniprot
proteins
pubmed
9736643
uniprot
proteins
sequence_length
495
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15361858, ECO:0000269|PubMed:7517498}; Multi-pass membrane protein {ECO:0000305}. Cell projection, axon {ECO:0000269|PubMed:20392939, ECO:0000269|PubMed:21233214, ECO:0000269|PubMed:26269648, ECO:0000269|PubMed:8046438, ECO:0000269|PubMed:8361541, ECO:0000269|PubMed:9581771, ECO:0000269|PubMed:9736643}. Membrane {ECO:0000269|PubMed:22158511}. Perikaryon {ECO:0000269|PubMed:12611922, ECO:0000269|PubMed:26269648, ECO:0000269|PubMed:8046438}. Cell projection, dendrite {ECO:0000269|PubMed:8046438}. Cell junction {ECO:0000269|PubMed:8046438}. Synapse {ECO:0000269|PubMed:8046438}. Cytoplasmic vesicle {ECO:0000269|PubMed:12611922}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P10499}. Presynaptic cell membrane {ECO:0000250|UniProtKB:P10499}. Presynapse {ECO:0000269|PubMed:21233214}. 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:0000269|PubMed:21233214}.
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