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Protein

Potassium voltage-gated channel subfamily A member 6

Gene

KCNA6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (PubMed:2347305, PubMed:14575698). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:2347305, PubMed:14575698). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (PubMed:2347305).By similarity2 Publications

GO - Molecular functioni

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

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 6
Alternative name(s):
Voltage-gated potassium channel HBK21 Publication
Voltage-gated potassium channel subunit Kv1.6
Gene namesi
Name:KCNA6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:6225. KCNA6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 171171CytoplasmicBy similarityAdd
BLAST
Transmembranei172 – 19322Helical; Name=Segment S1By similarityAdd
BLAST
Topological domaini194 – 26269ExtracellularBy similarityAdd
BLAST
Transmembranei263 – 28422Helical; Name=Segment S2By similarityAdd
BLAST
Topological domaini285 – 29511CytoplasmicBy similarityAdd
BLAST
Transmembranei296 – 31621Helical; Name=Segment S3By similarityAdd
BLAST
Topological domaini317 – 33721ExtracellularBy similarityAdd
BLAST
Transmembranei338 – 35821Helical; Voltage-sensor; Name=Segment S4By similarityAdd
BLAST
Topological domaini359 – 37315CytoplasmicBy similarityAdd
BLAST
Transmembranei374 – 39522Helical; Name=Segment S5By similarityAdd
BLAST
Topological domaini396 – 40914ExtracellularBy similarityAdd
BLAST
Intramembranei410 – 42112Helical; Name=Pore helixBy similarityAdd
BLAST
Intramembranei422 – 4298By similarity
Topological domaini430 – 4367ExtracellularBy similarity
Transmembranei437 – 46529Helical; Name=Segment S6By similarityAdd
BLAST
Topological domaini466 – 52964CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30022.

Chemistry

DrugBankiDB06637. Dalfampridine.

Polymorphism and mutation databases

BioMutaiKCNA6.
DMDMi116434.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 529529Potassium voltage-gated channel subfamily A member 6PRO_0000053990Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi285 – 2851S-palmitoyl cysteineSequence Analysis
Modified residuei511 – 5111Phosphoserine; by PKACurated

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP17658.
PRIDEiP17658.

PTM databases

PhosphoSiteiP17658.

Expressioni

Gene expression databases

BgeeiP17658.
CleanExiHS_KCNA6.
ExpressionAtlasiP17658. baseline and differential.
GenevisibleiP17658. HS.

Organism-specific databases

HPAiCAB011539.
HPA014418.

Interactioni

Subunit structurei

Homotetramer and heterotetramer of potassium channel proteins (By similarity). Interacts with KCNAB1 and KCNAB2 (By similarity).By similarityCurated

Protein-protein interaction databases

BioGridi109944. 9 interactions.
IntActiP17658. 1 interaction.
STRINGi9606.ENSP00000280684.

Structurei

3D structure databases

ProteinModelPortaliP17658.
SMRiP17658. Positions 41-469.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni360 – 37314S4-S5 linkerBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi422 – 4276Selectivity filterBy similarity
Motifi527 – 5293PDZ-bindingSequence Analysis

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.
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.
GeneTreeiENSGT00670000097647.
ENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiP17658.
KOiK04879.
OMAiDDSYTFH.
OrthoDBiEOG7M0NRD.
PhylomeDBiP17658.
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.
IPR004053. K_chnl_volt-dep_Kv1.6.
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.
PR01513. KV16CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.

Sequencei

Sequence statusi: Complete.

P17658-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRSEKSLTLA APGEVRGPEG EQQDAGDFPE AGGGGGCCSS ERLVINISGL
60 70 80 90 100
RFETQLRTLS LFPDTLLGDP GRRVRFFDPL RNEYFFDRNR PSFDAILYYY
110 120 130 140 150
QSGGRLRRPV NVPLDIFLEE IRFYQLGDEA LAAFREDEGC LPEGGEDEKP
160 170 180 190 200
LPSQPFQRQV WLLFEYPESS GPARGIAIVS VLVILISIVI FCLETLPQFR
210 220 230 240 250
VDGRGGNNGG VSRVSPVSRG SQEEEEDEDD SYTFHHGITP GEMGTGGSSS
260 270 280 290 300
LSTLGGSFFT DPFFLVETLC IVWFTFELLV RFSACPSKPA FFRNIMNIID
310 320 330 340 350
LVAIFPYFIT LGTELVQQQE QQPASGGGGQ NGQQAMSLAI LRVIRLVRVF
360 370 380 390 400
RIFKLSRHSK GLQILGKTLQ ASMRELGLLI FFLFIGVILF SSAVYFAEAD
410 420 430 440 450
DDDSLFPSIP DAFWWAVVTM TTVGYGDMYP MTVGGKIVGS LCAIAGVLTI
460 470 480 490 500
ALPVPVIVSN FNYFYHRETE QEEQGQYTHV TCGQPAPDLR ATDNGLGKPD
510 520
FPEANRERRP SYLPTPHRAY AEKRMLTEV
Length:529
Mass (Da):58,729
Last modified:August 1, 1990 - v1
Checksum:iCFF0710A1F9CD69F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17622 mRNA. Translation: CAA35623.1.
BC069355 mRNA. Translation: AAH69355.1.
CCDSiCCDS8534.1.
PIRiS12787.
RefSeqiNP_002226.1. NM_002235.3.
XP_005253743.1. XM_005253686.2.
UniGeneiHs.306190.

Genome annotation databases

EnsembliENST00000280684; ENSP00000280684; ENSG00000151079.
GeneIDi3742.
KEGGihsa:3742.
UCSCiuc001qng.3. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17622 mRNA. Translation: CAA35623.1.
BC069355 mRNA. Translation: AAH69355.1.
CCDSiCCDS8534.1.
PIRiS12787.
RefSeqiNP_002226.1. NM_002235.3.
XP_005253743.1. XM_005253686.2.
UniGeneiHs.306190.

3D structure databases

ProteinModelPortaliP17658.
SMRiP17658. Positions 41-469.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109944. 9 interactions.
IntActiP17658. 1 interaction.
STRINGi9606.ENSP00000280684.

Chemistry

BindingDBiP17658.
ChEMBLiCHEMBL2362996.
DrugBankiDB06637. Dalfampridine.
GuidetoPHARMACOLOGYi543.

PTM databases

PhosphoSiteiP17658.

Polymorphism and mutation databases

BioMutaiKCNA6.
DMDMi116434.

Proteomic databases

PaxDbiP17658.
PRIDEiP17658.

Protocols and materials databases

DNASUi3742.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000280684; ENSP00000280684; ENSG00000151079.
GeneIDi3742.
KEGGihsa:3742.
UCSCiuc001qng.3. human.

Organism-specific databases

CTDi3742.
GeneCardsiGC12P004918.
HGNCiHGNC:6225. KCNA6.
HPAiCAB011539.
HPA014418.
MIMi176257. gene.
neXtProtiNX_P17658.
PharmGKBiPA30022.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1226.
GeneTreeiENSGT00670000097647.
ENSGT00760000118846.
HOGENOMiHOG000231015.
HOVERGENiHBG052230.
InParanoidiP17658.
KOiK04879.
OMAiDDSYTFH.
OrthoDBiEOG7M0NRD.
PhylomeDBiP17658.
TreeFamiTF313103.

Enzyme and pathway databases

ReactomeiREACT_75770. Voltage gated Potassium channels.

Miscellaneous databases

ChiTaRSiKCNA6. human.
GeneWikiiKCNA6.
GenomeRNAii3742.
NextBioi14643.
PROiP17658.
SOURCEiSearch...

Gene expression databases

BgeeiP17658.
CleanExiHS_KCNA6.
ExpressionAtlasiP17658. baseline and differential.
GenevisibleiP17658. HS.

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.
IPR004053. K_chnl_volt-dep_Kv1.6.
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.
PR01513. KV16CHANNEL.
PR01491. KVCHANNEL.
PR01496. SHAKERCHANEL.
SMARTiSM00225. BTB. 1 hit.
[Graphical view]
SUPFAMiSSF54695. SSF54695. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and expression of a human voltage-gated potassium channel. A novel member of the RCK potassium channel family."
    Grupe A., Schroeter K.H., Ruppersberg J.P., Stocker M., Drewes T., Beckh S., Pongs O.
    EMBO J. 9:1749-1756(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION.
    Tissue: Brain.
  2. "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].
  3. "Human Kv1.6 current displays a C-type-like inactivation when re-expressed in cos-7 cells."
    Guihard G., Bellocq C., Grelet E., Escande D.
    Biochem. Biophys. Res. Commun. 311:83-89(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiKCNA6_HUMAN
AccessioniPrimary (citable) accession number: P17658
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: June 24, 2015
This is version 143 of the entry and version 1 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 12
    Human chromosome 12: 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.