Potassium voltage-gated channel subfamily A member 1

Details

Name
Potassium voltage-gated channel subfamily A member 1
Synonyms
  • Voltage-gated K(+) channel HuKI
  • Voltage-gated potassium channel HBK1
  • Voltage-gated potassium channel subunit Kv1.1
Gene Name
KCNA1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0019011|Potassium voltage-gated channel subfamily A member 1
MTVMSGENVDEASAAPGHPQDGSYPRQADHDDHECCERVVINISGLRFETQLKTLAQFPN
TLLGNPKKRMRYFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDMFSEEIKFY
ELGEEAMEKFREDEGFIKEEERPLPEKEYQRQVWLLFEYPESSGPARVIAIVSVMVILIS
IVIFCLETLPELKDDKDFTGTVHRIDNTTVIYNSNIFTDPFFIVETLCIIWFSFELVVRF
FACPSKTDFFKNIMNFIDIVAIIPYFITLGTEIAEQEGNQKGEQATSLAILRVIRLVRVF
RIFKLSRHSKGLQILGQTLKASMRELGLLIFFLFIGVILFSSAVYFAEAEEAESHFSSIP
DAFWWAVVSMTTVGYGDMYPVTIGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETE
GEEQAQLLHVSSPNLASDSDLSRRSSSTMSKSEYMEIEEDMNNSIAHYRQVNIRTANCTT
ANQNCVNKSKLLTDV
Number of residues
495
Molecular Weight
56465.01
Theoretical pI
4.82
GO Classification
Functions
delayed rectifier potassium channel activity / potassium channel activity / potassium ion transmembrane transporter activity / voltage-gated potassium channel activity
Processes
cell communication by electrical coupling / cellular protein localization / cellular response to magnesium ion / detection of mechanical stimulus involved in sensory perception of pain / detection of mechanical stimulus involved in sensory perception of touch / hippocampus development / magnesium ion homeostasis / neuroblast proliferation / neuromuscular process / neuronal action potential / neuronal signal transduction / potassium ion transmembrane transport / potassium ion transport / protein homooligomerization / regulation of membrane potential / regulation of muscle contraction / startle response / synaptic transmission
Components
apical plasma membrane / axon terminus / cell junction / cell surface / cytoplasmic membrane-bounded vesicle / cytosol / dendrite / endoplasmic reticulum / integral component of plasma membrane / juxtaparanode region of axon / neuronal cell body / paranode region of axon / perikaryon / plasma membrane / presynaptic membrane / synapse / voltage-gated potassium channel complex
General Function
Voltage-gated potassium channel activity
Specific 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). 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:19912772, PubMed:19968958, PubMed:19307729, PubMed:19903818). 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:23903368, PubMed:19307729).
Pfam Domain Function
Transmembrane Regions
165-186 221-242 254-274 288-308 324-345 387-415
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0019012|Potassium voltage-gated channel subfamily A member 1 (KCNA1)
ATGACGGTGATGTCTGGGGAGAACGTGGACGAGGCTTCGGCCGCCCCGGGCCACCCCCAG
GATGGCAGCTACCCCCGGCAGGCCGACCACGACGACCACGAGTGCTGCGAGCGCGTGGTG
ATCAACATCTCCGGGCTGCGCTTCGAGACGCAGCTCAAGACCCTGGCGCAGTTCCCCAAC
ACGCTGCTGGGCAACCCTAAGAAACGCATGCGCTACTTCGACCCCCTGAGGAACGAGTAC
TTCTTCGACCGCAACCGGCCCAGCTTCGACGCCATCCTCTACTACTACCAGTCCGGCGGC
CGCCTGCGGAGGCCGGTCAACGTGCCCCTGGACATGTTCTCCGAGGAGATCAAGTTTTAC
GAGTTGGGCGAGGAGGCCATGGAGAAGTTCCGGGAGGACGAGGGCTTCATCAAGGAGGAG
GAGCGCCCTCTGCCCGAGAAGGAGTACCAGCGCCAGGTGTGGCTGCTCTTCGAGTACCCC
GAGAGCTCGGGGCCCGCCAGGGTCATCGCCATCGTCTCCGTCATGGTCATCCTCATCTCC
ATCGTCATCTTTTGCCTGGAGACGCTCCCCGAGCTGAAGGATGACAAGGACTTCACGGGC
ACCGTCCACCGCATCGACAACACCACGGTCATCTACAATTCCAACATCTTCACAGACCCC
TTCTTCATCGTGGAAACGCTGTGTATCATCTGGTTCTCCTTCGAGCTGGTGGTGCGCTTC
TTCGCCTGCCCCAGCAAGACGGACTTCTTCAAAAACATCATGAACTTCATAGACATTGTG
GCCATCATTCCTTATTTCATCACGCTGGGCACCGAGATAGCTGAGCAGGAAGGAAACCAG
AAGGGCGAGCAGGCCACCTCCCTGGCCATCCTCAGGGTCATCCGCTTGGTAAGGGTTTTT
AGAATCTTCAAGCTCTCCCGCCACTCTAAGGGCCTCCAGATCCTGGGCCAGACCCTCAAA
GCTAGTATGAGAGAGCTAGGGCTGCTCATCTTTTTCCTCTTCATCGGGGTCATCCTGTTT
TCTAGTGCAGTGTACTTTGCCGAGGCGGAAGAAGCTGAGTCGCACTTCTCCAGTATCCCC
GATGCTTTCTGGTGGGCGGTGGTGTCCATGACCACTGTAGGATACGGTGACATGTACCCT
GTGACAATTGGAGGCAAGATCGTGGGCTCCTTGTGTGCCATCGCTGGTGTGCTAACAATT
GCCCTGCCCGTACCTGTCATTGTGTCCAATTTCAACTATTTCTACCACCGAGAAACTGAG
GGGGAAGAGCAGGCTCAGTTGCTCCACGTCAGTTCCCCTAACTTAGCCTCTGACAGTGAC
CTCAGTCGCCGCAGTTCCTCTACTATGAGCAAGTCTGAGTACATGGAGATCGAAGAGGAT
ATGAATAATAGCATAGCCCATTATAGACAGGTCAATATCAGAACTGCCAATTGCACCACT
GCTAACCAAAACTGCGTTAATAAGAGCAAGCTACTGACCGATGTTTAA
Chromosome Location
12
Locus
12p13
External Identifiers
ResourceLink
UniProtKB IDQ09470
UniProtKB Entry NameKCNA1_HUMAN
GenBank Protein ID186663
GenBank Gene IDL02750
GenAtlas IDKCNA1
HGNC IDHGNC:6218
General References
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  24. Imbrici P, D'Adamo MC, Kullmann DM, Pessia M: Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4-1.1/Kvbeta1.1 and Kv1.4-1.1/Kvbeta1.2. Eur J Neurosci. 2006 Dec;24(11):3073-83. [PubMed:17156368]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00753Isofluraneapproved, vet_approvedyesinducerDetails
DB01028Methoxyfluraneapproved, investigational, vet_approvedyesinducerDetails
DB01189DesfluraneapprovedyesinducerDetails
DB00321AmitriptylineapprovednoinhibitorDetails
DB06637DalfampridineapprovedyesantagonistDetails
DB08837Tetraethylammoniumexperimental, investigationalunknownblockerDetails
DB11640Amifampridineapproved, investigationalyesblockerDetails
DB00228Enfluraneapproved, investigational, vet_approvedunknowninhibitoractivatorDetails
DB01069Promethazineapproved, investigationalunknowninducerDetails
DB01110Miconazoleapproved, investigational, vet_approvedunknowninhibitorDetails