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Protein

Potassium voltage-gated channel subfamily KQT member 4

Gene

KCNQ4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

GO - Molecular functioni

  • delayed rectifier potassium channel activity Source: GO_Central
  • potassium channel activity Source: ProtInc

GO - Biological processi

  • inner ear morphogenesis Source: Ensembl
  • potassium ion transport Source: ProtInc
  • sensory perception of sound Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Potassium channel, Voltage-gated channel

Keywords - Biological processi

Hearing, Ion transport, Potassium transport, Transport

Keywords - Ligandi

Potassium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117013-MONOMER.
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

HGNCiHGNC:6298. KCNQ4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 97CytoplasmicAdd BLAST97
Transmembranei98 – 118Helical; Name=Segment S1Sequence analysisAdd BLAST21
Topological domaini119 – 131ExtracellularAdd BLAST13
Transmembranei132 – 152Helical; Name=Segment S2Sequence analysisAdd BLAST21
Topological domaini153 – 172CytoplasmicAdd BLAST20
Transmembranei173 – 193Helical; Name=Segment S3Sequence analysisAdd BLAST21
Topological domaini194 – 201Extracellular8
Transmembranei202 – 224Helical; Voltage-sensor; Name=Segment S4Sequence analysisAdd BLAST23
Topological domaini225 – 237CytoplasmicAdd BLAST13
Transmembranei238 – 258Helical; Name=Segment S5Sequence analysisAdd BLAST21
Topological domaini259 – 270ExtracellularAdd BLAST12
Intramembranei271 – 292Pore-forming; Name=Segment H5Sequence analysisAdd BLAST22
Topological domaini293 – 296Extracellular4
Transmembranei297 – 317Helical; Name=Segment S6Sequence analysisAdd BLAST21
Topological domaini318 – 695CytoplasmicAdd BLAST378

GO - Cellular componenti

Complete GO annotation...

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 rs80358276dbSNPEnsembl.1
Natural variantiVAR_008726276W → S in DFNA2A. 1 PublicationCorresponds to variant rs80358277dbSNPEnsembl.1
Natural variantiVAR_010937281L → S in DFNA2A. 1 PublicationCorresponds to variant rs80358278dbSNPEnsembl.1
Natural variantiVAR_008727285G → C in DFNA2A; loss of potassium selectivity of the pore. 1 PublicationCorresponds to variant rs28937588dbSNPEnsembl.1
Natural variantiVAR_001547285G → S in DFNA2A; dominant negative effect; abolishes potassium current. 1 PublicationCorresponds to variant rs28937588dbSNPEnsembl.1
Natural variantiVAR_065779287G → R in DFNA2A. 1 PublicationCorresponds to variant rs137853969dbSNPEnsembl.1
Natural variantiVAR_008728321G → S in DFNA2A. 1 PublicationCorresponds to variant rs28939710dbSNPEnsembl.1

Keywords - Diseasei

Deafness, Disease mutation, Non-syndromic deafness

Organism-specific databases

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

Chemistry databases

ChEMBLiCHEMBL3576.
DrugBankiDB04953. Ezogabine.
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.
PRIDEiP56696.

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.
CleanExiHS_KCNQ4.
ExpressionAtlasiP56696. baseline and differential.
GenevisibleiP56696. HS.

Organism-specific databases

HPAiHPA018305.

Interactioni

Subunit structurei

Homotetramer. May form heteromultimers with KCNQ3.1 Publication

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
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi526 – 548Combined sources23
Helixi612 – 637Combined sources26

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...

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.
OMAiWAFVYHV.
OrthoDBiEOG091G02ZT.
PhylomeDBiP56696.
TreeFamiTF315186.

Family and domain databases

InterProiIPR005821. Ion_trans_dom.
IPR003937. K_chnl_volt-dep_KCNQ.
IPR013821. K_chnl_volt-dep_KCNQ_C.
IPR015573. KCQN4.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PTHR11537:SF4. PTHR11537:SF4. 3 hits.
PfamiPF00520. Ion_trans. 1 hit.
PF03520. KCNQ_channel. 1 hit.
[Graphical view]
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.
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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010936274L → H in DFNA2A. 1 PublicationCorresponds to variant rs80358276dbSNPEnsembl.1
Natural variantiVAR_008726276W → S in DFNA2A. 1 PublicationCorresponds to variant rs80358277dbSNPEnsembl.1
Natural variantiVAR_010937281L → S in DFNA2A. 1 PublicationCorresponds to variant rs80358278dbSNPEnsembl.1
Natural variantiVAR_008727285G → C in DFNA2A; loss of potassium selectivity of the pore. 1 PublicationCorresponds to variant rs28937588dbSNPEnsembl.1
Natural variantiVAR_001547285G → S in DFNA2A; dominant negative effect; abolishes potassium current. 1 PublicationCorresponds to variant rs28937588dbSNPEnsembl.1
Natural variantiVAR_065779287G → R in DFNA2A. 1 PublicationCorresponds to variant rs137853969dbSNPEnsembl.1
Natural variantiVAR_008728321G → S in DFNA2A. 1 PublicationCorresponds to variant rs28939710dbSNPEnsembl.1
Natural variantiVAR_058971455H → Q.1 PublicationCorresponds to variant rs34287852dbSNPEnsembl.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]
GeneIDi9132.
KEGGihsa:9132.
UCSCiuc001cgh.2. human. [P56696-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.
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.
PRIDEiP56696.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9132.
DisGeNETi9132.
GeneCardsiKCNQ4.
GeneReviewsiKCNQ4.
H-InvDBHIX0200020.
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.
OMAiWAFVYHV.
OrthoDBiEOG091G02ZT.
PhylomeDBiP56696.
TreeFamiTF315186.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000117013-MONOMER.
ReactomeiR-HSA-1296072. Voltage gated Potassium channels.

Miscellaneous databases

ChiTaRSiKCNQ4. human.
EvolutionaryTraceiP56696.
GeneWikiiKCNQ4.
GenomeRNAii9132.
PROiP56696.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117013.
CleanExiHS_KCNQ4.
ExpressionAtlasiP56696. baseline and differential.
GenevisibleiP56696. HS.

Family and domain databases

InterProiIPR005821. Ion_trans_dom.
IPR003937. K_chnl_volt-dep_KCNQ.
IPR013821. K_chnl_volt-dep_KCNQ_C.
IPR015573. KCQN4.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERiPTHR11537. PTHR11537. 3 hits.
PTHR11537:SF4. PTHR11537:SF4. 3 hits.
PfamiPF00520. Ion_trans. 1 hit.
PF03520. KCNQ_channel. 1 hit.
[Graphical view]
PRINTSiPR00169. KCHANNEL.
PR01459. KCNQCHANNEL.
ProtoNetiSearch...

Entry informationi

Entry nameiKCNQ4_HUMAN
AccessioniPrimary (citable) accession number: P56696
Secondary accession number(s): O96025
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 22, 2009
Last modified: November 2, 2016
This is version 160 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

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

Similar proteinsi

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