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P56696 (KCNQ4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:KCNQ4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length695 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

Subunit structure

Homotetramer. May form heteromultimers with KCNQ3. Ref.5

Subcellular location

Basal cell membrane; Multi-pass membrane protein. Note: Situated at the basal membrane of cochlear outer hair cells By similarity.

Tissue specificity

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

Domain

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. Ref.5

The A-domain tail carries the major determinants of channel assembly specificity. Its coiled-coil region is Four-stranded. Ref.5

Involvement in disease

Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.6 Ref.7 Ref.8 Ref.9

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.

Sequence similarities

Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.4/KCNQ4 sub-subfamily. [View classification]

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P56696-1)

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.
Isoform 2 (identifier: P56696-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 695695Potassium voltage-gated channel subfamily KQT member 4
PRO_0000054037

Regions

Topological domain1 – 9797Cytoplasmic
Transmembrane98 – 11821Helical; Name=Segment S1; Potential
Topological domain119 – 13113Extracellular
Transmembrane132 – 15221Helical; Name=Segment S2; Potential
Topological domain153 – 17220Cytoplasmic
Transmembrane173 – 19321Helical; Name=Segment S3; Potential
Topological domain194 – 2018Extracellular
Transmembrane202 – 22423Helical; Voltage-sensor; Name=Segment S4; Potential
Topological domain225 – 23713Cytoplasmic
Transmembrane238 – 25821Helical; Name=Segment S5; Potential
Topological domain259 – 27012Extracellular
Intramembrane271 – 29222Pore-forming; Name=Segment H5; Potential
Topological domain293 – 2964Extracellular
Transmembrane297 – 31721Helical; Name=Segment S6; Potential
Topological domain318 – 695378Cytoplasmic
Region546 – 650105A-domain (Tetramerization)
Coiled coil610 – 64536 Ref.5
Motif283 – 2886Selectivity filter By similarity

Natural variations

Alternative sequence377 – 43054Missing in isoform 2.
VSP_001013
Natural variant2741L → H in DFNA2A. Ref.8
VAR_010936
Natural variant2761W → S in DFNA2A. Ref.6
VAR_008726
Natural variant2811L → S in DFNA2A. Ref.7
VAR_010937
Natural variant2851G → C in DFNA2A; loss of potassium selectivity of the pore. Ref.6
VAR_008727
Natural variant2851G → S in DFNA2A; dominant negative effect; abolishes potassium current. Ref.1
Corresponds to variant rs28937588 [ dbSNP | Ensembl ].
VAR_001547
Natural variant2871G → R in DFNA2A. Ref.9
VAR_065779
Natural variant3211G → S in DFNA2A. Ref.6
Corresponds to variant rs28939710 [ dbSNP | Ensembl ].
VAR_008728
Natural variant4551H → Q. Ref.1
Corresponds to variant rs34287852 [ dbSNP | Ensembl ].
VAR_058971

Secondary structure

..... 695
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 22, 2009. Version 2.
Checksum: 51390F5E00E8C157

FASTA69577,101
        10         20         30         40         50         60 
MAEAPPRRLG LGPPPGDAPR AELVALTAVQ SEQGEAGGGG SPRRLGLLGS PLPPGAPLPG 

        70         80         90        100        110        120 
PGSGSGSACG QRSSAAHKRY RRLQNWVYNV LERPRGWAFV YHVFIFLLVF SCLVLSVLST 

       130        140        150        160        170        180 
IQEHQELANE CLLILEFVMI VVFGLEYIVR VWSAGCCCRY RGWQGRFRFA RKPFCVIDFI 

       190        200        210        220        230        240 
VFVASVAVIA AGTQGNIFAT SALRSMRFLQ ILRMVRMDRR GGTWKLLGSV VYAHSKELIT 

       250        260        270        280        290        300 
AWYIGFLVLI FASFLVYLAE KDANSDFSSY ADSLWWGTIT LTTIGYGDKT PHTWLGRVLA 

       310        320        330        340        350        360 
AGFALLGISF FALPAGILGS GFALKVQEQH RQKHFEKRRM PAANLIQAAW RLYSTDMSRA 

       370        380        390        400        410        420 
YLTATWYYYD SILPSFRELA LLFEHVQRAR NGGLRPLEVR RAPVPDGAPS RYPPVATCHR 

       430        440        450        460        470        480 
PGSTSFCPGE SSRMGIKDRI RMGSSQRRTG PSKQHLAPPT MPTSPSSEQV GEATSPTKVQ 

       490        500        510        520        530        540 
KSWSFNDRTR FRASLRLKPR TSAEDAPSEE VAEEKSYQCE LTVDDIMPAV KTVIRSIRIL 

       550        560        570        580        590        600 
KFLVAKRKFK ETLRPYDVKD VIEQYSAGHL DMLGRIKSLQ TRVDQIVGRG PGDRKAREKG 

       610        620        630        640        650        660 
DKGPSDAEVV DEISMMGRVV KVEKQVQSIE HKLDLLLGFY SRCLRSGTSA SLGAVQVPLF 

       670        680        690 
DPDITSDYHS PVDHEDISVS AQTLSISRSV STNMD 

« Hide

Isoform 2 [UniParc].

Checksum: 769D085366D51552
Show »

FASTA64171,196

References

« Hide 'large scale' references
[1]"KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness."
Kubisch C., Schroeder B.C., Friedrich T., Luetjohann B., El-Amraoui A., Marlin S., Petit C., Jentsch T.J.
Cell 96:437-446(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), VARIANT DFNA2A SER-285, VARIANT GLN-455, CHARACTERIZATION OF VARIANT DFNA2A SER-285.
Tissue: Retina.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors."
Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Jentsch T.J., Brown D.A.
J. Physiol. (Lond.) 522:349-355(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[4]"KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology."
Soegaard R., Ljungstroem T., Pedersen K.A., Oelesen S.-P., Jensen B.S.
Am. J. Physiol. 280:C859-C866(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHARMACOLOGICAL CHARACTERIZATION, POSSIBLE FUNCTION.
[5]"Structural insight into KCNQ (Kv7) channel assembly and channelopathy."
Howard R.J., Clark K.A., Holton J.M., Minor D.L. Jr.
Neuron 53:663-675(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 610-640, SUBUNIT, DOMAIN COILED-COIL.
[6]"Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families."
Coucke P.J., Van Hauwe P., Kelley P.M., Kunst H., Schatteman I., Van Velzen D., Meyers J., Ensink R.J., Verstreken M., Declau F., Marres H., Kastury K., Bhasin S., McGuirt W.T., Smith R.J.H., Cremers C.W.R.J., Van de Heyning P., Willems P.J., Smith S.D., Van Camp G.
Hum. Mol. Genet. 8:1321-1328(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS DFNA2A SER-276; CYS-285 AND SER-321.
[7]"Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss."
Talebizadeh Z., Kelley P.M., Askew J.W., Beisel K.W., Smith S.D.
Hum. Mutat. 14:493-501(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA2A SER-281.
[8]"Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region."
Van Hauwe P., Coucke P.J., Ensink R.J., Huygen P., Cremers C.W.R.J., Van Camp G.
Am. J. Med. Genet. 93:184-187(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA2A HIS-274.
[9]"Autosomal dominant progressive sensorineural hearing loss due to a novel mutation in the KCNQ4 gene."
Arnett J., Emery S.B., Kim T.B., Boerst A.K., Lee K., Leal S.M., Lesperance M.M.
Arch. Otolaryngol. Head Neck Surg. 137:54-59(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT DFNA2A ARG-287.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF105202 mRNA. Translation: AAD14680.1.
AF105216 expand/collapse EMBL AC list , AF105203, AF105204, AF105205, AF105206, AF105207, AF105208, AF105209, AF105210, AF105211, AF105212, AF105213, AF105214, AF105215 Genomic DNA. Translation: AAD14681.1.
AC119677 Genomic DNA. No translation available.
CCDSCCDS456.1. [P56696-1]
RefSeqNP_004691.2. NM_004700.3. [P56696-1]
NP_751895.1. NM_172163.2. [P56696-2]
UniGeneHs.473058.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2OVCX-ray2.07A610-640[»]
4GOWX-ray2.60A522-593[»]
ProteinModelPortalP56696.
SMRP56696. Positions 119-334, 524-549, 611-640.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114580. 6 interactions.
STRING9606.ENSP00000262916.

Chemistry

ChEMBLCHEMBL3576.
GuidetoPHARMACOLOGY563.

Protein family/group databases

TCDB1.A.1.15.4. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteP56696.

Polymorphism databases

DMDM259016259.

Proteomic databases

PaxDbP56696.
PRIDEP56696.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000347132; ENSP00000262916; ENSG00000117013. [P56696-1]
ENST00000509682; ENSP00000423756; ENSG00000117013. [P56696-2]
GeneID9132.
KEGGhsa:9132.
UCSCuc001cgh.2. human. [P56696-1]
uc001cgi.2. human. [P56696-2]

Organism-specific databases

CTD9132.
GeneCardsGC01P041249.
GeneReviewsKCNQ4.
H-InvDBHIX0200020.
HGNCHGNC:6298. KCNQ4.
HPAHPA018305.
MIM600101. phenotype.
603537. gene.
neXtProtNX_P56696.
Orphanet90635. Autosomal dominant nonsyndromic sensorineural deafness type DFNA.
PharmGKBPA30076.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000220839.
HOVERGENHBG059014.
InParanoidP56696.
KOK04929.
OMAWAFVYHV.
OrthoDBEOG73804Z.
PhylomeDBP56696.
TreeFamTF315186.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

BgeeP56696.
CleanExHS_KCNQ4.
GenevestigatorP56696.

Family and domain databases

InterProIPR005821. Ion_trans_dom.
IPR003091. K_chnl.
IPR003937. K_chnl_volt-dep_KCNQ.
IPR013821. K_chnl_volt-dep_KCNQ_C.
IPR015573. KCQN4.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERPTHR11537. PTHR11537. 1 hit.
PTHR11537:SF4. PTHR11537:SF4. 1 hit.
PfamPF00520. Ion_trans. 1 hit.
PF03520. KCNQ_channel. 1 hit.
[Graphical view]
PRINTSPR00169. KCHANNEL.
PR01459. KCNQCHANNEL.
ProtoNetSearch...

Other

EvolutionaryTraceP56696.
GeneWikiKCNQ4.
GenomeRNAi9132.
NextBio34237.
PROP56696.
SOURCESearch...

Entry information

Entry nameKCNQ4_HUMAN
AccessionPrimary (citable) accession number: P56696
Secondary accession number(s): O96025
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 22, 2009
Last modified: July 9, 2014
This is version 138 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM