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Protein

Potassium voltage-gated channel subfamily A member 1

Gene

KCNA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 Mg2+ 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).By similarity11 Publications

Enzyme regulationi

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).2 Publications

GO - Molecular functioni

  • delayed rectifier potassium channel activity Source: UniProtKB
  • potassium channel activity Source: ProtInc
  • potassium ion transmembrane transporter activity Source: ProtInc
  • voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

  • cell communication by electrical coupling Source: UniProtKB
  • cellular protein localization Source: Ensembl
  • cellular response to magnesium ion Source: UniProtKB
  • chemical synaptic transmission Source: ProtInc
  • detection of mechanical stimulus involved in sensory perception of pain Source: UniProtKB
  • detection of mechanical stimulus involved in sensory perception of touch Source: UniProtKB
  • hippocampus development Source: Ensembl
  • magnesium ion homeostasis Source: UniProtKB
  • neuroblast proliferation Source: Ensembl
  • neuromuscular process Source: UniProtKB
  • neuronal action potential Source: UniProtKB
  • neuronal signal transduction Source: UniProtKB
  • potassium ion transmembrane transport Source: UniProtKB
  • potassium ion transport Source: ProtInc
  • protein homooligomerization Source: InterPro
  • regulation of membrane potential Source: UniProtKB
  • regulation of muscle contraction Source: UniProtKB
  • startle response Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000111262-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.

Protein family/group databases

TCDBi1.A.1.2.12. the voltage-gated ion channel (vic) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily A member 1
Alternative name(s):
Voltage-gated K(+) channel HuKI1 Publication
Voltage-gated potassium channel HBK11 Publication
Voltage-gated potassium channel subunit Kv1.1
Gene namesi
Name:KCNA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6218. KCNA1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 164CytoplasmicBy similarityAdd BLAST164
Transmembranei165 – 186Helical; Name=Segment S1By similarityAdd BLAST22
Topological domaini187 – 220ExtracellularBy similarityAdd BLAST34
Transmembranei221 – 242Helical; Name=Segment S2By similarityAdd BLAST22
Topological domaini243 – 253CytoplasmicBy similarityAdd BLAST11
Transmembranei254 – 274Helical; Name=Segment S3By similarityAdd BLAST21
Topological domaini275 – 287ExtracellularBy similarityAdd BLAST13
Transmembranei288 – 308Helical; Voltage-sensor; Name=Segment S4By similarityAdd BLAST21
Topological domaini309 – 323CytoplasmicBy similarityAdd BLAST15
Transmembranei324 – 345Helical; Name=Segment S5By similarityAdd BLAST22
Topological domaini346 – 359ExtracellularBy similarityAdd BLAST14
Intramembranei360 – 371Helical; Name=Pore helixBy similarityAdd BLAST12
Intramembranei372 – 379By similarity8
Topological domaini380 – 386ExtracellularBy similarity7
Transmembranei387 – 415Helical; Name=Segment S6By similarityAdd BLAST29
Topological domaini416 – 495CytoplasmicBy similarityAdd BLAST80

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • axon terminus Source: UniProtKB
  • cell junction Source: UniProtKB
  • cell surface Source: Ensembl
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • cytosol Source: UniProtKB
  • dendrite Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • juxtaparanode region of axon Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • paranode region of axon Source: UniProtKB
  • perikaryon Source: UniProtKB-SubCell
  • plasma membrane Source: Reactome
  • presynaptic membrane Source: UniProtKB
  • synapse Source: UniProtKB
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

Episodic ataxia 1 (EA1)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:160120
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001508174V → F in EA1. 2 PublicationsCorresponds to variant rs104894349dbSNPEnsembl.1
Natural variantiVAR_001509177I → R in EA1. 1 Publication1
Natural variantiVAR_020830184F → C in EA1; alters voltage dependence and kinetics of activation though not of C-type inactivation. 2 PublicationsCorresponds to variant rs104894357dbSNPEnsembl.1
Natural variantiVAR_001510226T → A in EA1. 1 PublicationCorresponds to variant rs104894354dbSNPEnsembl.1
Natural variantiVAR_020831226T → M in EA1. 1 PublicationCorresponds to variant rs28933383dbSNPEnsembl.1
Natural variantiVAR_037101226T → R in EA1; yields currents with a largely reduced amplitude. 1 PublicationCorresponds to variant rs28933383dbSNPEnsembl.1
Natural variantiVAR_001511239R → S in EA1. 1 PublicationCorresponds to variant rs104894348dbSNPEnsembl.1
Natural variantiVAR_001512249F → I in EA1. 1 PublicationCorresponds to variant rs104894356dbSNPEnsembl.1
Natural variantiVAR_020832325E → D in EA1; results in non-functional homomeric channels; accelerates recovery from N-type inactivation due to interaction with KCNAB1; slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 4 PublicationsCorresponds to variant rs104894353dbSNPEnsembl.1
Natural variantiVAR_020833329L → I in EA1. 1 Publication1
Natural variantiVAR_020834342S → I in EA1; phenotype without myokymia. 1 Publication1
Natural variantiVAR_001513404V → I in EA1; results in slower channel activation compared to wild-type; slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 3 PublicationsCorresponds to variant rs104894355dbSNPEnsembl.1
Natural variantiVAR_001514408V → A in EA1; channels have voltage dependence similar to that of wild-type channels but with faster kinetics and increased C-type inactivation; accelerates recovery from N-type inactivation due to interaction with KCNAB1; slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 4 PublicationsCorresponds to variant rs104894352dbSNPEnsembl.1
Myokymia isolated 1 (MK1)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:160120
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037100226T → K in MK1; induces a reduced efflux of potassium ions during depolarization which results in increased muscle cell activity; coexpression studies of the mutant protein with the wild-type protein produces significantly reduced currents suggesting a severe effect of the mutation. 1 PublicationCorresponds to variant rs28933383dbSNPEnsembl.1
Natural variantiVAR_037102242A → P in MK1; 10% reduction of mean peak current amplitudes compared to wil-dtype; mutant and wild-type expression together is consistent with a loss-of-function effect of the mutation. 1 PublicationCorresponds to variant rs28933381dbSNPEnsembl.1
Natural variantiVAR_037103244P → H in MK1; does not affect channel activity. 1 PublicationCorresponds to variant rs28933382dbSNPEnsembl.1
Natural variantiVAR_072397255N → D in MK1; strongly reduces the activity of homomeric channels with dominant negative effects on wild-type channels. 1 PublicationCorresponds to variant rs121918067dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi35 – 36CC → AA: No effect on palmitoylation, no effect on current kinetics. 1 Publication2
Mutagenesisi177I → N: Slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 1 Publication1
Mutagenesisi243C → A: Strongly decreases palmitoylation and alters current kinetics. 1 Publication1
Mutagenesisi255N → A, H or T: Slightly increases channel activity, but does not affect expression at the cell membrane. 1 Publication1
Mutagenesisi255N → E: Abolishes channel activity, but does not affect expression at the cell membrane. 1 Publication1
Mutagenesisi255N → Q: Strongly reduces channel activity, but does not affect expression at the cell membrane. 1 Publication1
Mutagenesisi255N → V: No effect on channel activity. 1 Publication1
Mutagenesisi446S → A: Impairs phosphorylation by PKA. 1 Publication1
Mutagenesisi446S → E: Impairs expression at the cell membrane. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi3736.
MalaCardsiKCNA1.
MIMi160120. phenotype.
OpenTargetsiENSG00000111262.
Orphaneti37612. Episodic ataxia type 1.
972. Hereditary continuous muscle fiber activity.
199326. Isolated autosomal dominant hypomagnesemia, Glaudemans type.
PharmGKBiPA30019.

Chemistry databases

ChEMBLiCHEMBL2309.
DrugBankiDB00321. Amitriptyline.
DB06637. Dalfampridine.
DB01189. Desflurane.
DB00228. Enflurane.
DB00753. Isoflurane.
DB01028. Methoxyflurane.
DB01115. Nifedipine.
DB01236. Sevoflurane.
GuidetoPHARMACOLOGYi538.

Polymorphism and mutation databases

BioMutaiKCNA1.
DMDMi223590092.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000539681 – 495Potassium voltage-gated channel subfamily A member 1Add BLAST495

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23PhosphoserineBy similarity1
Glycosylationi207N-linked (GlcNAc...)Sequence analysis1
Lipidationi243S-palmitoyl cysteine1 Publication1
Modified residuei322Phosphoserine; by PKASequence analysis1
Modified residuei437PhosphoserineBy similarity1
Modified residuei439PhosphoserineBy similarity1
Modified residuei446Phosphoserine; by PKA1 Publication1

Post-translational modificationi

N-glycosylated.By similarity
Palmitoylated on Cys-243; which may be required for membrane targeting.1 Publication
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).By similarity1 Publication

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

MaxQBiQ09470.
PaxDbiQ09470.
PeptideAtlasiQ09470.
PRIDEiQ09470.

PTM databases

iPTMnetiQ09470.
PhosphoSitePlusiQ09470.
SwissPalmiQ09470.

Expressioni

Tissue specificityi

Detected adjacent to nodes of Ranvier in juxtaparanodal zones in spinal cord nerve fibers, but also in paranodal regions in some myelinated spinal cord axons (at protein level) (PubMed:11086297). Detected in the islet of Langerhans (PubMed:21483673).2 Publications

Gene expression databases

BgeeiENSG00000111262.
CleanExiHS_KCNA1.
GenevisibleiQ09470. HS.

Organism-specific databases

HPAiCAB022365.

Interactioni

Subunit structurei

Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA2, KCNA4, KCNA5, KCNA6 and KCNA7 (PubMed:12077175, PubMed:17156368). Channel activity is regulated by interaction with the beta subunits KCNAB1 and KCNAB2 (PubMed:12077175, PubMed:17156368). Identified in a complex with KCNA2 and KCNAB2 (PubMed:11086297). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with LGI1 within a complex containing LGI1, KCNA4 and KCNAB1 (By similarity). Interacts (via N-terminus) with STX1A; this promotes channel inactivation (By similarity). Interacts (via N-terminus) with the heterodimer formed by GNB1 and GNG2; this promotes channel inactivation (By similarity). Can interact simultaneously with STX1A and the heterodimer formed by GNB1 and GNG2 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG; this inhibits channel activity (PubMed:19968958). Interacts with ANK3; this inhibits channel activity (PubMed:23903368).By similarityCurated4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dlg3Q629362EBI-8286599,EBI-349596From a different organism.
DLG4P783522EBI-8286599,EBI-80389

Protein-protein interaction databases

BioGridi109939. 7 interactors.
IntActiQ09470. 9 interactors.
MINTiMINT-1900397.
STRINGi9606.ENSP00000371985.

Chemistry databases

BindingDBiQ09470.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AFLmodel-A/B/C/D326-407[»]
ProteinModelPortaliQ09470.
SMRiQ09470.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 128Tetramerization domainBy similarityAdd BLAST128
Regioni310 – 323S4-S5 linkerBy similarityAdd BLAST14

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi372 – 377Selectivity filterBy similarity6
Motifi493 – 495PDZ-bindingBy similarity3

Domaini

The cytoplasmic N-terminus is important for tetramerization and for interaction with the beta subunits that promote rapid channel closure.By similarity
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.By similarity

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1545. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiQ09470.
KOiK04874.
OMAiIHRIDNT.
OrthoDBiEOG091G10NU.
PhylomeDBiQ09470.
TreeFamiTF313103.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004048. K_chnl_volt-dep_Kv1.1.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01508. KV11CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

Q09470-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTVMSGENVD EASAAPGHPQ DGSYPRQADH DDHECCERVV INISGLRFET
60 70 80 90 100
QLKTLAQFPN TLLGNPKKRM RYFDPLRNEY FFDRNRPSFD AILYYYQSGG
110 120 130 140 150
RLRRPVNVPL DMFSEEIKFY ELGEEAMEKF REDEGFIKEE ERPLPEKEYQ
160 170 180 190 200
RQVWLLFEYP ESSGPARVIA IVSVMVILIS IVIFCLETLP ELKDDKDFTG
210 220 230 240 250
TVHRIDNTTV IYNSNIFTDP FFIVETLCII WFSFELVVRF FACPSKTDFF
260 270 280 290 300
KNIMNFIDIV AIIPYFITLG TEIAEQEGNQ KGEQATSLAI LRVIRLVRVF
310 320 330 340 350
RIFKLSRHSK GLQILGQTLK ASMRELGLLI FFLFIGVILF SSAVYFAEAE
360 370 380 390 400
EAESHFSSIP DAFWWAVVSM TTVGYGDMYP VTIGGKIVGS LCAIAGVLTI
410 420 430 440 450
ALPVPVIVSN FNYFYHRETE GEEQAQLLHV SSPNLASDSD LSRRSSSTMS
460 470 480 490
KSEYMEIEED MNNSIAHYRQ VNIRTANCTT ANQNCVNKSK LLTDV
Length:495
Mass (Da):56,466
Last modified:February 10, 2009 - v2
Checksum:i0A1B1AB87BCDDEBA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti265Missing no nucleotide entry (PubMed:2128063).Curated1
Sequence conflicti315L → R no nucleotide entry (PubMed:2128063).Curated1
Sequence conflicti452S → Y in AAA36139 (PubMed:19912772).Curated1

RNA editingi

Edited at position 400.1 Publication
Partially edited. RNA editing varies from 17% in the caudate nucleus to 68% in the spinal cord and to 77% in the medulla.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001508174V → F in EA1. 2 PublicationsCorresponds to variant rs104894349dbSNPEnsembl.1
Natural variantiVAR_001509177I → R in EA1. 1 Publication1
Natural variantiVAR_020830184F → C in EA1; alters voltage dependence and kinetics of activation though not of C-type inactivation. 2 PublicationsCorresponds to variant rs104894357dbSNPEnsembl.1
Natural variantiVAR_020051204R → H.Corresponds to variant rs2229000dbSNPEnsembl.1
Natural variantiVAR_001510226T → A in EA1. 1 PublicationCorresponds to variant rs104894354dbSNPEnsembl.1
Natural variantiVAR_037100226T → K in MK1; induces a reduced efflux of potassium ions during depolarization which results in increased muscle cell activity; coexpression studies of the mutant protein with the wild-type protein produces significantly reduced currents suggesting a severe effect of the mutation. 1 PublicationCorresponds to variant rs28933383dbSNPEnsembl.1
Natural variantiVAR_020831226T → M in EA1. 1 PublicationCorresponds to variant rs28933383dbSNPEnsembl.1
Natural variantiVAR_037101226T → R in EA1; yields currents with a largely reduced amplitude. 1 PublicationCorresponds to variant rs28933383dbSNPEnsembl.1
Natural variantiVAR_001511239R → S in EA1. 1 PublicationCorresponds to variant rs104894348dbSNPEnsembl.1
Natural variantiVAR_037102242A → P in MK1; 10% reduction of mean peak current amplitudes compared to wil-dtype; mutant and wild-type expression together is consistent with a loss-of-function effect of the mutation. 1 PublicationCorresponds to variant rs28933381dbSNPEnsembl.1
Natural variantiVAR_037103244P → H in MK1; does not affect channel activity. 1 PublicationCorresponds to variant rs28933382dbSNPEnsembl.1
Natural variantiVAR_001512249F → I in EA1. 1 PublicationCorresponds to variant rs104894356dbSNPEnsembl.1
Natural variantiVAR_072397255N → D in MK1; strongly reduces the activity of homomeric channels with dominant negative effects on wild-type channels. 1 PublicationCorresponds to variant rs121918067dbSNPEnsembl.1
Natural variantiVAR_020832325E → D in EA1; results in non-functional homomeric channels; accelerates recovery from N-type inactivation due to interaction with KCNAB1; slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 4 PublicationsCorresponds to variant rs104894353dbSNPEnsembl.1
Natural variantiVAR_020833329L → I in EA1. 1 Publication1
Natural variantiVAR_020834342S → I in EA1; phenotype without myokymia. 1 Publication1
Natural variantiVAR_016805400I → V in RNA edited version. 1
Natural variantiVAR_001513404V → I in EA1; results in slower channel activation compared to wild-type; slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 3 PublicationsCorresponds to variant rs104894355dbSNPEnsembl.1
Natural variantiVAR_001514408V → A in EA1; channels have voltage dependence similar to that of wild-type channels but with faster kinetics and increased C-type inactivation; accelerates recovery from N-type inactivation due to interaction with KCNAB1; slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 4 PublicationsCorresponds to variant rs104894352dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L02750 mRNA. Translation: AAA36139.1.
AC006063 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88833.1.
BC101733 mRNA. Translation: AAI01734.1.
BC112180 mRNA. Translation: AAI12181.1.
CCDSiCCDS8535.1.
PIRiI57680.
RefSeqiNP_000208.2. NM_000217.2.
UniGeneiHs.416139.

Genome annotation databases

EnsembliENST00000382545; ENSP00000371985; ENSG00000111262.
GeneIDi3736.
KEGGihsa:3736.
UCSCiuc001qnh.4. human.

Keywords - Coding sequence diversityi

Polymorphism, RNA editing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L02750 mRNA. Translation: AAA36139.1.
AC006063 Genomic DNA. No translation available.
CH471116 Genomic DNA. Translation: EAW88833.1.
BC101733 mRNA. Translation: AAI01734.1.
BC112180 mRNA. Translation: AAI12181.1.
CCDSiCCDS8535.1.
PIRiI57680.
RefSeqiNP_000208.2. NM_000217.2.
UniGeneiHs.416139.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2AFLmodel-A/B/C/D326-407[»]
ProteinModelPortaliQ09470.
SMRiQ09470.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109939. 7 interactors.
IntActiQ09470. 9 interactors.
MINTiMINT-1900397.
STRINGi9606.ENSP00000371985.

Chemistry databases

BindingDBiQ09470.
ChEMBLiCHEMBL2309.
DrugBankiDB00321. Amitriptyline.
DB06637. Dalfampridine.
DB01189. Desflurane.
DB00228. Enflurane.
DB00753. Isoflurane.
DB01028. Methoxyflurane.
DB01115. Nifedipine.
DB01236. Sevoflurane.
GuidetoPHARMACOLOGYi538.

Protein family/group databases

TCDBi1.A.1.2.12. the voltage-gated ion channel (vic) superfamily.

PTM databases

iPTMnetiQ09470.
PhosphoSitePlusiQ09470.
SwissPalmiQ09470.

Polymorphism and mutation databases

BioMutaiKCNA1.
DMDMi223590092.

Proteomic databases

MaxQBiQ09470.
PaxDbiQ09470.
PeptideAtlasiQ09470.
PRIDEiQ09470.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382545; ENSP00000371985; ENSG00000111262.
GeneIDi3736.
KEGGihsa:3736.
UCSCiuc001qnh.4. human.

Organism-specific databases

CTDi3736.
DisGeNETi3736.
GeneCardsiKCNA1.
GeneReviewsiKCNA1.
HGNCiHGNC:6218. KCNA1.
HPAiCAB022365.
MalaCardsiKCNA1.
MIMi160120. phenotype.
176260. gene.
neXtProtiNX_Q09470.
OpenTargetsiENSG00000111262.
Orphaneti37612. Episodic ataxia type 1.
972. Hereditary continuous muscle fiber activity.
199326. Isolated autosomal dominant hypomagnesemia, Glaudemans type.
PharmGKBiPA30019.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1545. Eukaryota.
COG1226. LUCA.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiQ09470.
KOiK04874.
OMAiIHRIDNT.
OrthoDBiEOG091G10NU.
PhylomeDBiQ09470.
TreeFamiTF313103.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000111262-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.

Miscellaneous databases

ChiTaRSiKCNA1. human.
GeneWikiiKv1.1.
GenomeRNAii3736.
PROiQ09470.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111262.
CleanExiHS_KCNA1.
GenevisibleiQ09470. HS.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ_dom.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004048. K_chnl_volt-dep_Kv1.1.
IPR011333. SKP1/BTB/POZ.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01508. KV11CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNA1_HUMAN
AccessioniPrimary (citable) accession number: Q09470
Secondary accession number(s): A6NM83, Q3MIQ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: February 10, 2009
Last modified: November 30, 2016
This is version 175 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.