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Protein

Potassium voltage-gated channel subfamily A member 4

Gene

KCNA4

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. 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, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. 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 KCNA4 forms a potassium channel that opens in response to membrane depolarization, followed by rapid spontaneous channel closure (PubMed:19912772, PubMed:8495559). Likewise, a heterotetrameric channel formed by KCNA1 and KCNA4 shows rapid inactivation (PubMed:17156368).3 Publications

Enzyme regulationi

Inhibited by 4-aminopyridine (4-AP), but not by tetraethylammonium (TEA) and charybdotoxin (CTX).1 Publication

GO - Molecular functioni

  • potassium ion binding Source: InterPro
  • voltage-gated potassium channel activity Source: UniProtKB

GO - Biological processi

  • potassium ion transmembrane transport Source: UniProtKB
  • potassium ion transport Source: ProtInc
  • protein homooligomerization Source: InterPro
  • 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.

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily A member 4
Alternative name(s):
HPCN2
Voltage-gated K(+) channel HuKII1 Publication
Voltage-gated potassium channel HBK4
Voltage-gated potassium channel HK11 Publication
Voltage-gated potassium channel subunit Kv1.4
Gene namesi
Name:KCNA4
Synonyms:KCNA4L
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6222. KCNA4.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 304304CytoplasmicBy similarityAdd
BLAST
Transmembranei305 – 32622Helical; Name=Segment S1By similarityAdd
BLAST
Topological domaini327 – 37044ExtracellularBy similarityAdd
BLAST
Transmembranei371 – 39222Helical; Name=Segment S2By similarityAdd
BLAST
Topological domaini393 – 40311CytoplasmicBy similarityAdd
BLAST
Transmembranei404 – 42421Helical; Name=Segment S3By similarityAdd
BLAST
Topological domaini425 – 43915ExtracellularBy similarityAdd
BLAST
Transmembranei440 – 46021Helical; Voltage-sensor; Name=Segment S4By similarityAdd
BLAST
Topological domaini461 – 47515CytoplasmicBy similarityAdd
BLAST
Transmembranei476 – 49722Helical; Name=Segment S5By similarityAdd
BLAST
Topological domaini498 – 51114ExtracellularBy similarityAdd
BLAST
Intramembranei512 – 52312Helical; Name=Pore helixBy similarityAdd
BLAST
Intramembranei524 – 5318By similarity
Topological domaini532 – 5387ExtracellularBy similarity
Transmembranei539 – 56729Helical; Name=Segment S6By similarityAdd
BLAST
Topological domaini568 – 65386CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  • axon Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
  • voltage-gated potassium channel complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA207.

Chemistry

DrugBankiDB06637. Dalfampridine.

Polymorphism and mutation databases

BioMutaiKCNA4.
DMDMi313104127.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 653653Potassium voltage-gated channel subfamily A member 4PRO_0000053981Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei90 – 901Phosphoserine; by PKASequence Analysis
Glycosylationi352 – 3521N-linked (GlcNAc...)Sequence Analysis
Modified residuei599 – 5991Phosphoserine; by PKASequence Analysis

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP22459.
PRIDEiP22459.

PTM databases

PhosphoSiteiP22459.

Expressioni

Tissue specificityi

Detected in heart ventricle.1 Publication

Gene expression databases

BgeeiP22459.
CleanExiHS_KCNA4.
GenevestigatoriP22459.

Organism-specific databases

HPAiCAB001977.
HPA016422.

Interactioni

Subunit structurei

Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity). Binds PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with SIGMAR1 (By similarity). Detected in a complex with KCNA1 (By similarity). Interacts with KCNA2 (By similarity). Part of a complex containing KCNA1, KCNAB1 and LGI1 (By similarity). Interacts (via cytoplasmic N-terminal domain) with KCNRG (PubMed:19968958).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Dlg3Q629364EBI-631235,EBI-349596From a different organism.
DLG4P783522EBI-631235,EBI-80389
Dlg4P310163EBI-631235,EBI-375655From a different organism.

Protein-protein interaction databases

BioGridi109942. 18 interactions.
IntActiP22459. 6 interactions.
MINTiMINT-200816.
STRINGi9606.ENSP00000328511.

Structurei

3D structure databases

ProteinModelPortaliP22459.
SMRiP22459. Positions 1-75, 175-571.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni462 – 47514S4-S5 linkerBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi524 – 5296Selectivity filterBy similarity
Motifi651 – 6533PDZ-bindingBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi62 – 654Poly-His
Compositional biasi123 – 13715Poly-GluAdd
BLAST
Compositional biasi162 – 1654Poly-Gly
Compositional biasi433 – 4364Poly-Gln

Domaini

The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.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.
InParanoidiP22459.
KOiK04877.
OMAiKKAHHRQ.
OrthoDBiEOG7M0NRD.
PhylomeDBiP22459.
TreeFamiTF313103.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
1.20.5.600. 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.
IPR020467. K_chnl_volt-dep_Kv1.4.
IPR012897. K_chnl_volt-dep_Kv1.4_TID.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF07941. K_channel_TID. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01511. KV14CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

P22459-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEVAMVSAES SGCNSHMPYG YAAQARARER ERLAHSRAAA AAAVAAATAA
60 70 80 90 100
VEGSGGSGGG SHHHHQSRGA CTSHDPQSSR GSRRRRRQRS EKKKAHYRQS
110 120 130 140 150
SFPHCSDLMP SGSEEKILRE LSEEEEDEEE EEEEEEEGRF YYSEDDHGDE
160 170 180 190 200
CSYTDLLPQD EGGGGYSSVR YSDCCERVVI NVSGLRFETQ MKTLAQFPET
210 220 230 240 250
LLGDPEKRTQ YFDPLRNEYF FDRNRPSFDA ILYYYQSGGR LKRPVNVPFD
260 270 280 290 300
IFTEEVKFYQ LGEEALLKFR EDEGFVREEE DRALPENEFK KQIWLLFEYP
310 320 330 340 350
ESSSPARGIA IVSVLVILIS IVIFCLETLP EFRDDRDLVM ALSAGGHGGL
360 370 380 390 400
LNDTSAPHLE NSGHTIFNDP FFIVETVCIV WFSFEFVVRC FACPSQALFF
410 420 430 440 450
KNIMNIIDIV SILPYFITLG TDLAQQQGGG NGQQQQAMSF AILRIIRLVR
460 470 480 490 500
VFRIFKLSRH SKGLQILGHT LRASMRELGL LIFFLFIGVI LFSSAVYFAE
510 520 530 540 550
ADEPTTHFQS IPDAFWWAVV TMTTVGYGDM KPITVGGKIV GSLCAIAGVL
560 570 580 590 600
TIALPVPVIV SNFNYFYHRE TENEEQTQLT QNAVSCPYLP SNLLKKFRSS
610 620 630 640 650
TSSSLGDKSE YLEMEEGVKE SLCAKEEKCQ GKGDDSETDK NNCSNAKAVE

TDV
Length:653
Mass (Da):73,257
Last modified:November 30, 2010 - v2
Checksum:i5E511DB704CCA013
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti38 – 381A → R in AAA60034 (PubMed:2263489).Curated
Sequence conflicti42 – 421A → R in AAA60034 (PubMed:2263489).Curated
Sequence conflicti84 – 885RRRRQ → EEEAT in AAA60034 (PubMed:2263489).Curated
Sequence conflicti304 – 3041S → D in AAA60034 (PubMed:2263489).Curated
Sequence conflicti542 – 5421S → V in AAA60034 (PubMed:2263489).Curated
Sequence conflicti631 – 6311G → A in AAA60034 (PubMed:2263489).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55514 mRNA. Translation: AAA60034.1.
M60450 mRNA. Translation: AAA61275.1.
L02751 mRNA. Translation: AAA36140.1.
AC124657 Genomic DNA. No translation available.
CCDSiCCDS41629.1.
PIRiA39922.
RefSeqiNP_002224.1. NM_002233.3.
UniGeneiHs.592002.

Genome annotation databases

EnsembliENST00000328224; ENSP00000328511; ENSG00000182255.
GeneIDi3739.
KEGGihsa:3739.
UCSCiuc001msk.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55514 mRNA. Translation: AAA60034.1.
M60450 mRNA. Translation: AAA61275.1.
L02751 mRNA. Translation: AAA36140.1.
AC124657 Genomic DNA. No translation available.
CCDSiCCDS41629.1.
PIRiA39922.
RefSeqiNP_002224.1. NM_002233.3.
UniGeneiHs.592002.

3D structure databases

ProteinModelPortaliP22459.
SMRiP22459. Positions 1-75, 175-571.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109942. 18 interactions.
IntActiP22459. 6 interactions.
MINTiMINT-200816.
STRINGi9606.ENSP00000328511.

Chemistry

BindingDBiP22459.
ChEMBLiCHEMBL2362996.
DrugBankiDB06637. Dalfampridine.

PTM databases

PhosphoSiteiP22459.

Polymorphism and mutation databases

BioMutaiKCNA4.
DMDMi313104127.

Proteomic databases

PaxDbiP22459.
PRIDEiP22459.

Protocols and materials databases

DNASUi3739.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328224; ENSP00000328511; ENSG00000182255.
GeneIDi3739.
KEGGihsa:3739.
UCSCiuc001msk.3. human.

Organism-specific databases

CTDi3739.
GeneCardsiGC11M030031.
H-InvDBHIX0036152.
HGNCiHGNC:6222. KCNA4.
HPAiCAB001977.
HPA016422.
MIMi176266. gene.
neXtProtiNX_P22459.
PharmGKBiPA207.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1226.
GeneTreeiENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiP22459.
KOiK04877.
OMAiKKAHHRQ.
OrthoDBiEOG7M0NRD.
PhylomeDBiP22459.
TreeFamiTF313103.

Enzyme and pathway databases

ReactomeiREACT_75770. Voltage gated Potassium channels.

Miscellaneous databases

GeneWikiiKCNA4.
GenomeRNAii3739.
NextBioi14635.
PROiP22459.
SOURCEiSearch...

Gene expression databases

BgeeiP22459.
CleanExiHS_KCNA4.
GenevestigatoriP22459.

Family and domain databases

Gene3Di1.20.120.350. 1 hit.
1.20.5.600. 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.
IPR020467. K_chnl_volt-dep_Kv1.4.
IPR012897. K_chnl_volt-dep_Kv1.4_TID.
IPR003131. T1-type_BTB.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 1 hit.
PfamiPF02214. BTB_2. 1 hit.
PF00520. Ion_trans. 1 hit.
PF07941. K_channel_TID. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01511. KV14CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4."
    Philipson L.H., Schaefer K., Lamendola J., Bell G.I., Steiner D.F.
    Nucleic Acids Res. 18:7160-7160(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Skeletal muscle.
  2. "Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle."
    Tamkun M.M., Knoth K.M., Walbridge J.A., Kroemer H., Roden D.M., Glover D.M.
    FASEB J. 5:331-337(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Heart.
  3. "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.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "Heteromultimeric assembly of human potassium channels. Molecular basis of a transient outward current?"
    Po S., Roberds S., Snyders D.J., Tamkun M.M., Bennett P.B.
    Circ. Res. 72:1326-1336(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  6. "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: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT.
  7. "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, SUBCELLULAR LOCATION.
  8. "NMR structure of inactivation gates from mammalian voltage-dependent potassium channels."
    Antz C., Geyer M., Fakler B., Schott M.K., Guy H.R., Frank R., Ruppersberg J.P., Kalbitzer H.R.
    Nature 385:272-275(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1-37.

Entry informationi

Entry nameiKCNA4_HUMAN
AccessioniPrimary (citable) accession number: P22459
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: November 30, 2010
Last modified: April 29, 2015
This is version 145 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. 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.