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Protein

Potassium voltage-gated channel subfamily KQT member 4

Gene

KCNQ4

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

Functioni

Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors.

Miscellaneous

Mutagenesis experiments were carried out by expressing in Xenopus oocytes KCNQ4 mutants either individually (homomultimers) or in combination with wild-type KCNQ4 (mut/wt homomultimers) in a ratio of 1:1, to mimic the situation in a heterozygous DFNA2 patient.

GO - Molecular functioni

  • calmodulin binding Source: GO_Central
  • delayed rectifier potassium channel activity Source: GO_Central
  • potassium channel activity Source: ProtInc
  • voltage-gated potassium channel activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionIon channel, Potassium channel, Voltage-gated channel
Biological processHearing, Ion transport, Potassium transport, Transport
LigandPotassium

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels

Protein family/group databases

TCDBi1.A.1.15.4 the voltage-gated ion channel (vic) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium voltage-gated channel subfamily KQT member 4
Alternative name(s):
KQT-like 4
Potassium channel subunit alpha KvLQT4
Voltage-gated potassium channel subunit Kv7.4
Gene namesi
Name:KCNQ4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117013.14
HGNCiHGNC:6298 KCNQ4
MIMi603537 gene
neXtProtiNX_P56696

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 97CytoplasmicSequence analysisAdd BLAST97
Transmembranei98 – 118Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini119 – 131ExtracellularSequence analysisAdd BLAST13
Transmembranei132 – 152Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini153 – 172CytoplasmicSequence analysisAdd BLAST20
Transmembranei173 – 193Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini194 – 201ExtracellularSequence analysis8
Transmembranei202 – 224Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST23
Topological domaini225 – 237CytoplasmicSequence analysisAdd BLAST13
Transmembranei238 – 258Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini259 – 270ExtracellularSequence analysisAdd BLAST12
Intramembranei271 – 292Pore-forming; Name=Segment H5Sequence analysisAdd BLAST22
Topological domaini293 – 296ExtracellularSequence analysis4
Transmembranei297 – 317Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini318 – 695CytoplasmicSequence analysisAdd BLAST378

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Deafness, autosomal dominant, 2A (DFNA2A)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
See also OMIM:600101
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010936274L → H in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs80358276EnsemblClinVar.1
Natural variantiVAR_008726276W → S in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs80358277EnsemblClinVar.1
Natural variantiVAR_010937281L → S in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs80358278EnsemblClinVar.1
Natural variantiVAR_008727285G → C in DFNA2A; loss of potassium selectivity of the pore. 1 PublicationCorresponds to variant dbSNP:rs28937588EnsemblClinVar.1
Natural variantiVAR_001547285G → S in DFNA2A; dominant negative effect; abolishes potassium current. 1 PublicationCorresponds to variant dbSNP:rs28937588EnsemblClinVar.1
Natural variantiVAR_065779287G → R in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs137853969EnsemblClinVar.1
Natural variantiVAR_008728321G → S in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs28939710EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi123E → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi124H → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi125Q → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi126E → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi194Q → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi196N → Q: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi205S → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi210Q → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi213R → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi216R → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi261K → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi262D → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi266D → G: Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation. 1 Publication1
Mutagenesisi268S → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi272D → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi288D → G: Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation. 1 Publication1
Mutagenesisi290T → V: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi292H → G: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi295L → V: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1
Mutagenesisi298V → T: No effect on inhibition by potassium channel toxin SsTX. 1 Publication1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

DisGeNETi9132
GeneReviewsiKCNQ4
MalaCardsiKCNQ4
MIMi600101 phenotype
OpenTargetsiENSG00000117013
Orphaneti90635 Autosomal dominant non-syndromic sensorineural deafness type DFNA
PharmGKBiPA30076

Chemistry databases

ChEMBLiCHEMBL3576
DrugBankiDB04953 Ezogabine
DB06089 ICA-105665
GuidetoPHARMACOLOGYi563

Polymorphism and mutation databases

BioMutaiKCNQ4
DMDMi259016259

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000540371 – 695Potassium voltage-gated channel subfamily KQT member 4Add BLAST695

Proteomic databases

PaxDbiP56696
PeptideAtlasiP56696
PRIDEiP56696
ProteomicsDBi56934
56935 [P56696-2]

PTM databases

iPTMnetiP56696
PhosphoSitePlusiP56696

Expressioni

Tissue specificityi

Expressed in the outer, but not the inner, sensory hair cells of the cochlea. Slightly expressed in heart, brain and skeletal muscle.

Gene expression databases

BgeeiENSG00000117013 Expressed in 128 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_KCNQ4
ExpressionAtlasiP56696 baseline and differential
GenevisibleiP56696 HS

Organism-specific databases

HPAiHPA018305

Interactioni

Subunit structurei

Homotetramer. May form heteromultimers with KCNQ3. Interacts with HSP90AB1; promotes cell surface expression of KCNQ4 (PubMed:23431407).2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114580, 6 interactors
STRINGi9606.ENSP00000262916

Chemistry databases

BindingDBiP56696

Structurei

Secondary structure

1695
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP56696
SMRiP56696
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56696

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni546 – 650A-domain (Tetramerization)Add BLAST105

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili610 – 645Add BLAST36

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi283 – 288Selectivity filterBy similarity6

Domaini

The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.By similarity
The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded.1 Publication

Sequence similaritiesi

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1419 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00550000074513
HOGENOMiHOG000220839
HOVERGENiHBG059014
InParanoidiP56696
KOiK04929
OMAiHQEFANE
OrthoDBiEOG091G02ZT
PhylomeDBiP56696
TreeFamiTF315186

Family and domain databases

InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR003937 K_chnl_volt-dep_KCNQ
IPR013821 K_chnl_volt-dep_KCNQ_C
IPR015573 KCQN4
IPR028325 VG_K_chnl
PANTHERiPTHR11537 PTHR11537, 1 hit
PTHR11537:SF4 PTHR11537:SF4, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
PF03520 KCNQ_channel, 1 hit
PRINTSiPR00169 KCHANNEL
PR01459 KCNQCHANNEL

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P56696-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAEAPPRRLG LGPPPGDAPR AELVALTAVQ SEQGEAGGGG SPRRLGLLGS
60 70 80 90 100
PLPPGAPLPG PGSGSGSACG QRSSAAHKRY RRLQNWVYNV LERPRGWAFV
110 120 130 140 150
YHVFIFLLVF SCLVLSVLST IQEHQELANE CLLILEFVMI VVFGLEYIVR
160 170 180 190 200
VWSAGCCCRY RGWQGRFRFA RKPFCVIDFI VFVASVAVIA AGTQGNIFAT
210 220 230 240 250
SALRSMRFLQ ILRMVRMDRR GGTWKLLGSV VYAHSKELIT AWYIGFLVLI
260 270 280 290 300
FASFLVYLAE KDANSDFSSY ADSLWWGTIT LTTIGYGDKT PHTWLGRVLA
310 320 330 340 350
AGFALLGISF FALPAGILGS GFALKVQEQH RQKHFEKRRM PAANLIQAAW
360 370 380 390 400
RLYSTDMSRA YLTATWYYYD SILPSFRELA LLFEHVQRAR NGGLRPLEVR
410 420 430 440 450
RAPVPDGAPS RYPPVATCHR PGSTSFCPGE SSRMGIKDRI RMGSSQRRTG
460 470 480 490 500
PSKQHLAPPT MPTSPSSEQV GEATSPTKVQ KSWSFNDRTR FRASLRLKPR
510 520 530 540 550
TSAEDAPSEE VAEEKSYQCE LTVDDIMPAV KTVIRSIRIL KFLVAKRKFK
560 570 580 590 600
ETLRPYDVKD VIEQYSAGHL DMLGRIKSLQ TRVDQIVGRG PGDRKAREKG
610 620 630 640 650
DKGPSDAEVV DEISMMGRVV KVEKQVQSIE HKLDLLLGFY SRCLRSGTSA
660 670 680 690
SLGAVQVPLF DPDITSDYHS PVDHEDISVS AQTLSISRSV STNMD
Length:695
Mass (Da):77,101
Last modified:September 22, 2009 - v2
Checksum:i51390F5E00E8C157
GO
Isoform 2 (identifier: P56696-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     377-430: Missing.

Show »
Length:641
Mass (Da):71,196
Checksum:i769D085366D51552
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y6N7H0Y6N7_HUMAN
Potassium voltage-gated channel sub...
KCNQ4
556Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010936274L → H in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs80358276EnsemblClinVar.1
Natural variantiVAR_008726276W → S in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs80358277EnsemblClinVar.1
Natural variantiVAR_010937281L → S in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs80358278EnsemblClinVar.1
Natural variantiVAR_008727285G → C in DFNA2A; loss of potassium selectivity of the pore. 1 PublicationCorresponds to variant dbSNP:rs28937588EnsemblClinVar.1
Natural variantiVAR_001547285G → S in DFNA2A; dominant negative effect; abolishes potassium current. 1 PublicationCorresponds to variant dbSNP:rs28937588EnsemblClinVar.1
Natural variantiVAR_065779287G → R in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs137853969EnsemblClinVar.1
Natural variantiVAR_008728321G → S in DFNA2A. 1 PublicationCorresponds to variant dbSNP:rs28939710EnsemblClinVar.1
Natural variantiVAR_058971455H → Q1 PublicationCorresponds to variant dbSNP:rs34287852EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001013377 – 430Missing in isoform 2. 1 PublicationAdd BLAST54

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF105202 mRNA Translation: AAD14680.1
AF105216
, AF105203, AF105204, AF105205, AF105206, AF105207, AF105208, AF105209, AF105210, AF105211, AF105212, AF105213, AF105214, AF105215 Genomic DNA Translation: AAD14681.1
AC119677 Genomic DNA No translation available.
CCDSiCCDS456.1 [P56696-1]
RefSeqiNP_004691.2, NM_004700.3 [P56696-1]
NP_751895.1, NM_172163.2 [P56696-2]
UniGeneiHs.473058

Genome annotation databases

EnsembliENST00000347132; ENSP00000262916; ENSG00000117013 [P56696-1]
ENST00000509682; ENSP00000423756; ENSG00000117013 [P56696-2]
ENST00000642618; ENSP00000494128; ENSG00000117013 [P56696-1]
GeneIDi9132
KEGGihsa:9132
UCSCiuc001cgh.2 human [P56696-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Hereditary hearing loss homepage

Gene page

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF105202 mRNA Translation: AAD14680.1
AF105216
, AF105203, AF105204, AF105205, AF105206, AF105207, AF105208, AF105209, AF105210, AF105211, AF105212, AF105213, AF105214, AF105215 Genomic DNA Translation: AAD14681.1
AC119677 Genomic DNA No translation available.
CCDSiCCDS456.1 [P56696-1]
RefSeqiNP_004691.2, NM_004700.3 [P56696-1]
NP_751895.1, NM_172163.2 [P56696-2]
UniGeneiHs.473058

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OVCX-ray2.07A610-640[»]
4GOWX-ray2.60A522-593[»]
ProteinModelPortaliP56696
SMRiP56696
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114580, 6 interactors
STRINGi9606.ENSP00000262916

Chemistry databases

BindingDBiP56696
ChEMBLiCHEMBL3576
DrugBankiDB04953 Ezogabine
DB06089 ICA-105665
GuidetoPHARMACOLOGYi563

Protein family/group databases

TCDBi1.A.1.15.4 the voltage-gated ion channel (vic) superfamily

PTM databases

iPTMnetiP56696
PhosphoSitePlusiP56696

Polymorphism and mutation databases

BioMutaiKCNQ4
DMDMi259016259

Proteomic databases

PaxDbiP56696
PeptideAtlasiP56696
PRIDEiP56696
ProteomicsDBi56934
56935 [P56696-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000347132; ENSP00000262916; ENSG00000117013 [P56696-1]
ENST00000509682; ENSP00000423756; ENSG00000117013 [P56696-2]
ENST00000642618; ENSP00000494128; ENSG00000117013 [P56696-1]
GeneIDi9132
KEGGihsa:9132
UCSCiuc001cgh.2 human [P56696-1]

Organism-specific databases

CTDi9132
DisGeNETi9132
EuPathDBiHostDB:ENSG00000117013.14
GeneCardsiKCNQ4
GeneReviewsiKCNQ4
H-InvDBiHIX0200020
HGNCiHGNC:6298 KCNQ4
HPAiHPA018305
MalaCardsiKCNQ4
MIMi600101 phenotype
603537 gene
neXtProtiNX_P56696
OpenTargetsiENSG00000117013
Orphaneti90635 Autosomal dominant non-syndromic sensorineural deafness type DFNA
PharmGKBiPA30076
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1419 Eukaryota
COG1226 LUCA
GeneTreeiENSGT00550000074513
HOGENOMiHOG000220839
HOVERGENiHBG059014
InParanoidiP56696
KOiK04929
OMAiHQEFANE
OrthoDBiEOG091G02ZT
PhylomeDBiP56696
TreeFamiTF315186

Enzyme and pathway databases

ReactomeiR-HSA-1296072 Voltage gated Potassium channels

Miscellaneous databases

ChiTaRSiKCNQ4 human
EvolutionaryTraceiP56696
GeneWikiiKCNQ4
GenomeRNAii9132
PROiPR:P56696
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117013 Expressed in 128 organ(s), highest expression level in pigmented layer of retina
CleanExiHS_KCNQ4
ExpressionAtlasiP56696 baseline and differential
GenevisibleiP56696 HS

Family and domain databases

InterProiView protein in InterPro
IPR005821 Ion_trans_dom
IPR003937 K_chnl_volt-dep_KCNQ
IPR013821 K_chnl_volt-dep_KCNQ_C
IPR015573 KCQN4
IPR028325 VG_K_chnl
PANTHERiPTHR11537 PTHR11537, 1 hit
PTHR11537:SF4 PTHR11537:SF4, 1 hit
PfamiView protein in Pfam
PF00520 Ion_trans, 1 hit
PF03520 KCNQ_channel, 1 hit
PRINTSiPR00169 KCHANNEL
PR01459 KCNQCHANNEL
ProtoNetiSearch...

Entry informationi

Entry nameiKCNQ4_HUMAN
AccessioniPrimary (citable) accession number: P56696
Secondary accession number(s): O96025
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 22, 2009
Last modified: November 7, 2018
This is version 172 of the entry and version 2 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

Documents

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