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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 20mM tetraethylammonium (TEA), but not by charybdotoxin (CTX)(PubMed:19912772). Inhibited by dendrotoxin (DTX) (PubMed:19307729).2 Publications

GO - Molecular functioni

  1. delayed rectifier potassium channel activity Source: UniProtKB
  2. potassium channel activity Source: ProtInc
  3. potassium ion transmembrane transporter activity Source: ProtInc
  4. voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

  1. cell communication by electrical coupling Source: UniProtKB
  2. cellular response to magnesium ion Source: UniProtKB
  3. detection of mechanical stimulus involved in sensory perception of pain Source: UniProtKB
  4. detection of mechanical stimulus involved in sensory perception of touch Source: UniProtKB
  5. magnesium ion homeostasis Source: UniProtKB
  6. neuromuscular process Source: UniProtKB
  7. neuronal action potential Source: UniProtKB
  8. neuronal signal transduction Source: UniProtKB
  9. potassium ion transmembrane transport Source: UniProtKB
  10. potassium ion transport Source: ProtInc
  11. protein homooligomerization Source: InterPro
  12. regulation of membrane potential Source: UniProtKB
  13. regulation of muscle contraction Source: UniProtKB
  14. synaptic transmission Source: Reactome
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

ReactomeiREACT_75770. 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
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:6218. KCNA1.

Subcellular locationi

Cell membrane 9 Publications; Multi-pass membrane protein Curated. Membrane 1 Publication. Cell projectionaxon 1 Publication. Cytoplasmic vesicle 1 Publication. Perikaryon By similarity. Endoplasmic reticulum By similarity. Cell projectiondendrite By similarity. Cell junction By similarity. Cell junctionsynapse By similarity. Cell junctionsynapsepresynaptic cell membrane By similarity
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). Detected at axon terminals (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 164164CytoplasmicBy similarityAdd
BLAST
Transmembranei165 – 18622Helical; Name=Segment S1By similarityAdd
BLAST
Topological domaini187 – 22034ExtracellularBy similarityAdd
BLAST
Transmembranei221 – 24222Helical; Name=Segment S2By similarityAdd
BLAST
Topological domaini243 – 25311CytoplasmicBy similarityAdd
BLAST
Transmembranei254 – 27421Helical; Name=Segment S3By similarityAdd
BLAST
Topological domaini275 – 28713ExtracellularBy similarityAdd
BLAST
Transmembranei288 – 30821Helical; Voltage-sensor; Name=Segment S4By similarityAdd
BLAST
Topological domaini309 – 32315CytoplasmicBy similarityAdd
BLAST
Transmembranei324 – 34522Helical; Name=Segment S5By similarityAdd
BLAST
Topological domaini346 – 35914ExtracellularBy similarityAdd
BLAST
Intramembranei360 – 37112Helical; Name=Pore helixBy similarityAdd
BLAST
Intramembranei372 – 3798By similarity
Topological domaini380 – 3867ExtracellularBy similarity
Transmembranei387 – 41529Helical; Name=Segment S6By similarityAdd
BLAST
Topological domaini416 – 49580CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. apical plasma membrane Source: Ensembl
  2. axon terminus Source: UniProtKB
  3. cell junction Source: UniProtKB
  4. cell surface Source: Ensembl
  5. cytosol Source: UniProtKB
  6. dendrite Source: UniProtKB
  7. endoplasmic reticulum Source: UniProtKB
  8. integral component of membrane Source: GO_Central
  9. integral component of plasma membrane Source: UniProtKB
  10. juxtaparanode region of axon Source: UniProtKB
  11. neuronal cell body Source: UniProtKB
  12. paranode region of axon Source: UniProtKB
  13. plasma membrane Source: Reactome
  14. presynaptic membrane Source: UniProtKB
  15. synapse Source: UniProtKB
  16. 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 18 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti174 – 1741V → F in EA1. 2 Publications
VAR_001508
Natural varianti177 – 1771I → R in EA1. 1 Publication
VAR_001509
Natural varianti184 – 1841F → C in EA1; alters voltage dependence and kinetics of activation though not of C-type inactivation. 2 Publications
VAR_020830
Natural varianti226 – 2261T → A in EA1. 1 Publication
VAR_001510
Natural varianti226 – 2261T → M in EA1. 1 Publication
VAR_020831
Natural varianti226 – 2261T → R in EA1; yields currents with a largely reduced amplitude. 1 Publication
Corresponds to variant rs28933383 [ dbSNP | Ensembl ].
VAR_037101
Natural varianti239 – 2391R → S in EA1. 1 Publication
VAR_001511
Natural varianti249 – 2491F → I in EA1. 1 Publication
VAR_001512
Natural varianti325 – 3251E → 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 Publications
VAR_020832
Natural varianti329 – 3291L → I in EA1. 1 Publication
VAR_020833
Natural varianti342 – 3421S → I in EA1; phenotype without myokymia. 1 Publication
VAR_020834
Natural varianti404 – 4041V → 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 Publications
VAR_001513
Natural varianti408 – 4081V → 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 Publications
VAR_001514
Myokymia isolated 13 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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti226 – 2261T → 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 Publication
Corresponds to variant rs28933383 [ dbSNP | Ensembl ].
VAR_037100
Natural varianti242 – 2421A → 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 Publication
Corresponds to variant rs28933381 [ dbSNP | Ensembl ].
VAR_037102
Natural varianti244 – 2441P → H in MK1; does not affect channel activity. 1 Publication
Corresponds to variant rs28933382 [ dbSNP | Ensembl ].
VAR_037103
Natural varianti255 – 2551N → D in MK1; strongly reduces the activity of homomeric channels with dominant negative efffects on wild-type channels. 1 Publication
VAR_072397

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi35 – 362CC → AA: No effect on palmitoylation, no effect on current kinetics. 1 Publication
Mutagenesisi177 – 1771I → N: Slows down N-type inactivation of heteromeric channels formed by KCNA1 and KCNA4. 1 Publication
Mutagenesisi243 – 2431C → A: Strongly decreases palmitoylation and alters current kinetics. 1 Publication
Mutagenesisi255 – 2551N → A, H or T: Slightly increases channel activity, but does not affect expression at the cell membrane. 1 Publication
Mutagenesisi255 – 2551N → E: Abolishes channel activity, but does not affect expression at the cell membrane. 1 Publication
Mutagenesisi255 – 2551N → Q: Strongly reduces channel activity, but does not affect expression at the cell membrane. 1 Publication
Mutagenesisi255 – 2551N → V: No effect on channel activity. 1 Publication
Mutagenesisi446 – 4461S → A: Impairs phosphorylation by PKA. 1 Publication
Mutagenesisi446 – 4461S → E: Impairs expression at the cell membrane. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 495495Potassium voltage-gated channel subfamily A member 1PRO_0000053968Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi207 – 2071N-linked (GlcNAc...)Sequence Analysis
Lipidationi243 – 2431S-palmitoyl cysteine1 Publication
Modified residuei322 – 3221Phosphoserine; by PKASequence Analysis
Modified residuei446 – 4461Phosphoserine; by PKA1 Publication

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

PaxDbiQ09470.
PRIDEiQ09470.

PTM databases

PhosphoSiteiQ09470.

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

BgeeiQ09470.
CleanExiHS_KCNA1.
GenevestigatoriQ09470.

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 interactions.
IntActiQ09470. 3 interactions.
MINTiMINT-1900397.
STRINGi9606.ENSP00000228858.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AFLmodel-A/B/C/D326-407[»]
ProteinModelPortaliQ09470.
SMRiQ09470. Positions 36-419.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 128128Tetramerization domainBy similarityAdd
BLAST
Regioni310 – 32314S4-S5 linkerBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi372 – 3776Selectivity filterBy similarity
Motifi493 – 4953PDZ-bindingBy similarity

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

eggNOGiCOG1226.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiQ09470.
KOiK04874.
OMAiIHRIDNT.
OrthoDBiEOG7M0NRD.
PhylomeDBiQ09470.
TreeFamiTF313103.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004048. K_chnl_volt-dep_Kv1.1.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti265 – 2651Missing no nucleotide entry (PubMed:2128063).Curated
Sequence conflicti315 – 3151L → R no nucleotide entry (PubMed:2128063).Curated
Sequence conflicti452 – 4521S → Y in AAA36139 (PubMed:19912772).Curated

RNA editingi

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti174 – 1741V → F in EA1. 2 Publications
VAR_001508
Natural varianti177 – 1771I → R in EA1. 1 Publication
VAR_001509
Natural varianti184 – 1841F → C in EA1; alters voltage dependence and kinetics of activation though not of C-type inactivation. 2 Publications
VAR_020830
Natural varianti204 – 2041R → H.
Corresponds to variant rs2229000 [ dbSNP | Ensembl ].
VAR_020051
Natural varianti226 – 2261T → A in EA1. 1 Publication
VAR_001510
Natural varianti226 – 2261T → 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 Publication
Corresponds to variant rs28933383 [ dbSNP | Ensembl ].
VAR_037100
Natural varianti226 – 2261T → M in EA1. 1 Publication
VAR_020831
Natural varianti226 – 2261T → R in EA1; yields currents with a largely reduced amplitude. 1 Publication
Corresponds to variant rs28933383 [ dbSNP | Ensembl ].
VAR_037101
Natural varianti239 – 2391R → S in EA1. 1 Publication
VAR_001511
Natural varianti242 – 2421A → 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 Publication
Corresponds to variant rs28933381 [ dbSNP | Ensembl ].
VAR_037102
Natural varianti244 – 2441P → H in MK1; does not affect channel activity. 1 Publication
Corresponds to variant rs28933382 [ dbSNP | Ensembl ].
VAR_037103
Natural varianti249 – 2491F → I in EA1. 1 Publication
VAR_001512
Natural varianti255 – 2551N → D in MK1; strongly reduces the activity of homomeric channels with dominant negative efffects on wild-type channels. 1 Publication
VAR_072397
Natural varianti325 – 3251E → 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 Publications
VAR_020832
Natural varianti329 – 3291L → I in EA1. 1 Publication
VAR_020833
Natural varianti342 – 3421S → I in EA1; phenotype without myokymia. 1 Publication
VAR_020834
Natural varianti400 – 4001I → V in RNA edited version.
VAR_016805
Natural varianti404 – 4041V → 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 Publications
VAR_001513
Natural varianti408 – 4081V → 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 Publications
VAR_001514

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.3. human.

Polymorphism databases

DMDMi223590092.

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
EntryMethodResolution (Å)ChainPositionsPDBsum
2AFLmodel-A/B/C/D326-407[»]
ProteinModelPortaliQ09470.
SMRiQ09470. Positions 36-419.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109939. 7 interactions.
IntActiQ09470. 3 interactions.
MINTiMINT-1900397.
STRINGi9606.ENSP00000228858.

Chemistry

BindingDBiQ09470.
ChEMBLiCHEMBL2362996.
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

PhosphoSiteiQ09470.

Polymorphism databases

DMDMi223590092.

Proteomic databases

PaxDbiQ09470.
PRIDEiQ09470.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000382545; ENSP00000371985; ENSG00000111262.
GeneIDi3736.
KEGGihsa:3736.
UCSCiuc001qnh.3. human.

Organism-specific databases

CTDi3736.
GeneCardsiGC12P005019.
GeneReviewsiKCNA1.
HGNCiHGNC:6218. KCNA1.
HPAiCAB022365.
MIMi160120. phenotype.
176260. gene.
neXtProtiNX_Q09470.
Orphaneti37612. Episodic ataxia type 1.
972. Hereditary continuous muscle fiber activity.
199326. Isolated autosomal dominant hypomagnesemia, Glaudemans type.
PharmGKBiPA30019.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1226.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiQ09470.
KOiK04874.
OMAiIHRIDNT.
OrthoDBiEOG7M0NRD.
PhylomeDBiQ09470.
TreeFamiTF313103.

Enzyme and pathway databases

ReactomeiREACT_75770. Voltage gated Potassium channels.

Miscellaneous databases

ChiTaRSiKCNA1. human.
GeneWikiiKv1.1.
GenomeRNAii3736.
NextBioi14621.
PROiQ09470.
SOURCEiSearch...

Gene expression databases

BgeeiQ09470.
CleanExiHS_KCNA1.
GenevestigatoriQ09470.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
InterProiIPR000210. BTB/POZ-like.
IPR011333. BTB/POZ_fold.
IPR027359. Channel_four-helix_dom.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
IPR003968. K_chnl_volt-dep_Kv.
IPR003972. K_chnl_volt-dep_Kv1.
IPR004048. K_chnl_volt-dep_Kv1.1.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Human potassium channel genes: molecular cloning and functional expression."
    Ramaswami M., Gautam M., Kamb A., Rudy B., Tanouye M.A., Mathew M.K.
    Mol. Cell. Neurosci. 1:214-223(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
    Tissue: Brain.
  2. "The finished DNA sequence of human chromosome 12."
    Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
    , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
    Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain cortex.
  5. "Cloning and characterization of a cDNA encoding a human brain potassium channel."
    Freeman S.N., Conley E.C., Brennand J.C., Russell N.J.W., Brammar W.J.
    Biochem. Soc. Trans. 18:891-892(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 263-315.
  6. "Subunit composition and novel localization of K+ channels in spinal cord."
    Rasband M.N., Trimmer J.S.
    J. Comp. Neurol. 429:166-176(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KCNA2 AND KCNAB2, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  7. "Nervous system targets of RNA editing identified by comparative genomics."
    Hoopengardner B., Bhalla T., Staber C., Reenan R.
    Science 301:832-836(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: RNA EDITING OF POSITION 400.
  8. "The human Kv1.1 channel is palmitoylated, modulating voltage sensing: Identification of a palmitoylation consensus sequence."
    Gubitosi-Klug R.A., Mancuso D.J., Gross R.W.
    Proc. Natl. Acad. Sci. U.S.A. 102:5964-5968(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PALMITOYLATION AT CYS-243, MUTAGENESIS OF 35-CYS--CYS-36 AND CYS-243, FUNCTION, SUBCELLULAR LOCATION.
  9. "Ionic channel function in action potential generation: current perspective."
    Baranauskas G.
    Mol. Neurobiol. 35:129-150(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. "Potassium channel regulator KCNRG regulates surface expression of Shaker-type potassium channels."
    Usman H., Mathew M.K.
    Biochem. Biophys. Res. Commun. 391:1301-1305(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KCNRG, FUNCTION, SUBCELLULAR LOCATION.
  11. "Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1."
    Tomlinson S.E., Tan S.V., Kullmann D.M., Griggs R.C., Burke D., Hanna M.G., Bostock H.
    Brain 133:3530-3540(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  12. "Evidence for presence and functional effects of Kv1.1 channels in beta-cells: general survey and results from mceph/mceph mice."
    Ma Z., Lavebratt C., Almgren M., Portwood N., Forsberg L.E., Branstrom R., Berglund E., Falkmer S., Sundler F., Wierup N., Bjorklund A.
    PLoS ONE 6:E18213-E18213(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  13. Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-446, MUTAGENESIS OF SER-446.
  14. "Ankyrin-3 is a novel binding partner of the voltage-gated potassium channel Kv1.1 implicated in renal magnesium handling."
    San-Cristobal P., Lainez S., Dimke H., de Graaf M.J., Hoenderop J.G., Bindels R.J.
    Kidney Int. 85:94-102(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ANK3, FUNCTION, SUBCELLULAR LOCATION.
  15. "Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1."
    Browne D.L., Gancher S.T., Nutt J.G., Brunt E.R.P., Smith E.A., Kramer P., Litt M.
    Nat. Genet. 8:136-140(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS EA1 PHE-174; SER-239; ILE-249 AND ALA-408.
  16. "Identification of two new KCNA1 mutations in episodic ataxia/myokymia families."
    Browne D.L., Brunt E.R.P., Griggs R.C., Nutt J.G., Gancher S.T., Smith E.A., Litt M.
    Hum. Mol. Genet. 4:1671-1672(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS EA1 PHE-174; CYS-184 AND ASP-325.
  17. "Episodic ataxia results from voltage-dependent potassium channels with altered functions."
    Adelman J.P., Bond C.T., Pessia M., Maylie J.
    Neuron 15:1449-1454(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS EA1 CYS-184; ASP-325 AND ALA-408.
  18. "Episodic ataxia and myokymia syndrome: a new mutation of potassium channel gene Kv1.1."
    Comu S., Giuliani M., Narayanan V.
    Ann. Neurol. 40:684-687(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EA1 MET-226.
  19. Cited for: VARIANTS EA1 ARG-177; ALA-226 AND ILE-404.
  20. "A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy."
    Zuberi S.M., Eunson L.H., Spauschus A., De Silva R., Tolmie J., Wood N.W., McWilliam R.C., Stephenson J.P.B., Kullmann D.M., Hanna M.G.
    Brain 122:817-825(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EA1 ARG-226, CHARACTERIZATION OF VARIANT EA1 ARG-226.
  21. "Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability."
    Eunson L.H., Rea R., Zuberi S.M., Youroukos S., Panayiotopoulos C.P., Liguori R., Avoni P., McWilliam R.C., Stephenson J.B.P., Hanna M.G., Kullmann D.M., Spauschus A.
    Ann. Neurol. 48:647-656(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MK1 PRO-242 AND HIS-244, VARIANT EA1 ILE-404, CHARACTERIZATION OF VARIANTS MK1 PRO-242 AND HIS-244, CHARACTERIZATION OF VARIANT EA1 ILE-404, FUNCTION.
  22. "Identification of a novel missense mutation L329I in the episodic ataxia type 1 gene KCNA1 -- a challenging problem."
    Knight M.A., Storey E., McKinlay Gardner R.J., Hand P., Forrest S.M.
    Hum. Mutat. 16:374-374(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EA1 ILE-329.
  23. "Episodic ataxia type 1 mutations in the human Kv1.1 potassium channel alter hKvbeta 1-induced N-type inactivation."
    Maylie B., Bissonnette E., Virk M., Adelman J.P., Maylie J.G.
    J. Neurosci. 22:4786-4793(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS EA1 ASP-325 AND ALA-408, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH KCNAB1.
  24. "A novel mutation in KCNA1 causes episodic ataxia without myokymia."
    Lee H., Wang H., Jen J.C., Sabatti C., Baloh R.W., Nelson S.F.
    Hum. Mutat. 24:536-536(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EA1 ILE-342.
  25. "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."
    Imbrici P., D'Adamo M.C., Kullmann D.M., Pessia M.
    Eur. J. Neurosci. 24:3073-3083(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS EA1 ASP-325; ILE-404 AND ALA-408, MUTAGENESIS OF ILE-177, FUNCTION, SUBCELLULAR LOCATION.
  26. "Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia."
    Chen H., von Hehn C., Kaczmarek L.K., Ment L.R., Pober B.R., Hisama F.M.
    Neurogenetics 8:131-135(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MK1 LYS-226, CHARACTERIZATION OF VARIANT MK1 LYS-226, FUNCTION, SUBCELLULAR LOCATION.
  27. "A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia."
    Glaudemans B., van der Wijst J., Scola R.H., Lorenzoni P.J., Heister A., van der Kemp A.W., Knoers N.V., Hoenderop J.G., Bindels R.J.
    J. Clin. Invest. 119:936-942(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MK1 ASP-255, CHARACTERIZATION OF VARIANT MK1 ASP-255, FUNCTION, SUBCELLULAR LOCATION, ENZYME REGULATION.
  28. "Functional analysis of the Kv1.1 N255D mutation associated with autosomal dominant hypomagnesemia."
    van der Wijst J., Glaudemans B., Venselaar H., Nair A.V., Forst A.L., Hoenderop J.G., Bindels R.J.
    J. Biol. Chem. 285:171-178(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANT MK1 ASP-255, MUTAGENESIS OF ASN-255, FUNCTION, SUBCELLULAR LOCATION.

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: March 4, 2015
This is version 158 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

External Data

Dasty 3

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 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.