Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O43525 (KCNQ3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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 3
Alternative name(s):
KQT-like 3
Potassium channel subunit alpha KvLQT3
Voltage-gated potassium channel subunit Kv7.3
Gene names
Name:KCNQ3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length872 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probably important in the regulation of neuronal excitability. Associates with KCNQ2 or KCNQ5 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs.

Subunit structure

Heteromultimer with KCNQ2 or KCNQ5. May associate with KCNE2.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Predominantly expressed in brain.

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.

Involvement in disease

Seizures, benign familial neonatal 2 (BFNS2) [MIM:121201]: A disorder characterized by clusters of seizures occurring in the first days of life. Most patients have spontaneous remission by 12 months of age and show normal psychomotor development. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.5 Ref.16 Ref.17

Miscellaneous

Mutagenesis experiments were carried out in Xenopus oocytes by coexpression of either KCNQ3(mut) and KCNQ2 at the ratio of 1:1, or of KCNQ3(mut), KCNQ3(wt) and KCNQ2 at the ratio of 1:1:2, to mimic the situation in a heterozygous patient with BFNC2 disease.

Sequence similarities

Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.3/KCNQ3 sub-subfamily. [View classification]

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43525-1)

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: O43525-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-9: MGLKARRAA → MKPAEHATM
     10-129: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 872872Potassium voltage-gated channel subfamily KQT member 3
PRO_0000054034

Regions

Transmembrane122 – 14221Helical; Name=Segment S1; Potential
Transmembrane153 – 17321Helical; Name=Segment S2; Potential
Transmembrane197 – 21721Helical; Name=Segment S3; Potential
Transmembrane226 – 24722Helical; Voltage-sensor; Name=Segment S4; Potential
Transmembrane262 – 28221Helical; Name=Segment S5; Potential
Intramembrane304 – 32421Pore-forming; Name=Segment H5; Potential
Transmembrane331 – 35121Helical; Name=Segment S6; Potential
Motif316 – 3216Selectivity filter By similarity
Compositional bias13 – 2412Poly-Gly

Amino acid modifications

Modified residue2461Phosphothreonine Ref.15

Natural variations

Alternative sequence1 – 99MGLKARRAA → MKPAEHATM in isoform 2.
VSP_044906
Alternative sequence10 – 129120Missing in isoform 2.
VSP_044907
Natural variant3051D → G in BFNS2; reduces the maximal heteromeric current by approx. 40% with no alteration in voltage dependence of activation or deactivation kinetics. Ref.17
VAR_026994
Natural variant3091W → R in BFNS2. Ref.16
VAR_010935
Natural variant3101G → V in BFNS2; about 50% reduction of wild-type heteromeric current; ratio of 1:1; or 20%; ratio of 1:1:2. Ref.1 Ref.5 Ref.17
VAR_001546
Natural variant4141E → G.
Corresponds to variant rs2303995 [ dbSNP | Ensembl ].
VAR_053859
Natural variant4681N → S Has no statistically significant effect on the current or biophysical properties of the heteromeric channel. Ref.17
Corresponds to variant rs118192252 [ dbSNP | Ensembl ].
VAR_026995

Experimental info

Mutagenesis2461T → A: No effect on current or expression. Ref.15
Mutagenesis2461T → D: Abolishes currents without reducing channel protein expression. Ref.15
Mutagenesis3181G → S: >50% Reduction of wt heteromeric current; ratio of 1:1 and 1:1:2. Ref.1
Sequence conflict2331Q → L in BAG58996. Ref.3

Sequences

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

Last modified July 15, 1999. Version 2.
Checksum: BB79C69EE8591A84

FASTA87296,742
        10         20         30         40         50         60 
MGLKARRAAG AAGGGGDGGG GGGGAANPAG GDAAAAGDEE RKVGLAPGDV EQVTLALGAG 

        70         80         90        100        110        120 
ADKDGTLLLE GGGRDEGQRR TPQGIGLLAK TPLSRPVKRN NAKYRRIQTL IYDALERPRG 

       130        140        150        160        170        180 
WALLYHALVF LIVLGCLILA VLTTFKEYET VSGDWLLLLE TFAIFIFGAE FALRIWAAGC 

       190        200        210        220        230        240 
CCRYKGWRGR LKFARKPLCM LDIFVLIASV PVVAVGNQGN VLATSLRSLR FLQILRMLRM 

       250        260        270        280        290        300 
DRRGGTWKLL GSAICAHSKE LITAWYIGFL TLILSSFLVY LVEKDVPEVD AQGEEMKEEF 

       310        320        330        340        350        360 
ETYADALWWG LITLATIGYG DKTPKTWEGR LIAATFSLIG VSFFALPAGI LGSGLALKVQ 

       370        380        390        400        410        420 
EQHRQKHFEK RRKPAAELIQ AAWRYYATNP NRIDLVATWR FYESVVSFPF FRKEQLEAAS 

       430        440        450        460        470        480 
SQKLGLLDRV RLSNPRGSNT KGKLFTPLNV DAIEESPSKE PKPVGLNNKE RFRTAFRMKA 

       490        500        510        520        530        540 
YAFWQSSEDA GTGDPMAEDR GYGNDFPIED MIPTLKAAIR AVRILQFRLY KKKFKETLRP 

       550        560        570        580        590        600 
YDVKDVIEQY SAGHLDMLSR IKYLQTRIDM IFTPGPPSTP KHKKSQKGSA FTFPSQQSPR 

       610        620        630        640        650        660 
NEPYVARPST SEIEDQSMMG KFVKVERQVQ DMGKKLDFLV DMHMQHMERL QVQVTEYYPT 

       670        680        690        700        710        720 
KGTSSPAEAE KKEDNRYSDL KTIICNYSET GPPEPPYSFH QVTIDKVSPY GFFAHDPVNL 

       730        740        750        760        770        780 
PRGGPSSGKV QATPPSSATT YVERPTVLPI LTLLDSRVSC HSQADLQGPY SDRISPRQRR 

       790        800        810        820        830        840 
SITRDSDTPL SLMSVNHEEL ERSPSGFSIS QDRDDYVFGP NGGSSWMREK RYLAEGETDT 

       850        860        870 
DTDPFTPSGS MPLSSTGDGI SDSVWTPSNK PI 

« Hide

Isoform 2 [UniParc].

Checksum: BC8C18D5BE17F0DB
Show »

FASTA75284,804

References

« Hide 'large scale' references
[1]"Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy."
Schroeder B.C., Kubisch C., Stein V., Jentsch T.J.
Nature 396:687-690(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION OF VARIANT BFNS2 VAL-310, MUTAGENESIS OF GLY-318.
Tissue: Brain.
[2]"Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy."
Yang W.-P., Levesque P.C., Little W.A., Conder M.L., Ramakrishnan P., Neubauer M.G., Blanar M.A.
J. Biol. Chem. 273:19419-19423(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION.
Tissue: Brain and Fetal brain.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Thalamus.
[4]"DNA sequence and analysis of human chromosome 8."
Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. expand/collapse author list , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family."
Charlier C., Singh N.A., Ryan S.G., Lewis T.B., Reus B.E., Leach R.J., Leppert M.
Nat. Genet. 18:53-55(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 48-872 (ISOFORM 1), VARIANT BFNS2 VAL-310.
Tissue: Brain.
[6]"Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell."
Selyanko A.A., Hadley J.K., Wood I.C., Abogadie F.C., Delmas P., Buckley N.J., London B., Brown D.A.
J. Neurosci. 19:7742-7756(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN M-LIKE CURRENT.
[7]"M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit."
Tinel N., Diochot S., Lauritzen I., Barhanin J., Lazdunski M., Borsotto M.
FEBS Lett. 480:137-141(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION WITH KCNE2.
[8]"Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy."
Schwake M., Pusch M., Kharkovets T., Jentsch T.J.
J. Biol. Chem. 275:13343-13348(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SURFACE EXPRESSION OF HETEROMERS.
[9]"Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current."
Shapiro M.S., Roche J.P., Kaftan E.J., Cruzblanca H., Mackie K., Hille B.
J. Neurosci. 20:1710-1721(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[10]"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.
[11]"Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine."
Main M.J., Cryan J.E., Dupere J.R., Cox B., Clare J.J., Burbidge S.A.
Mol. Pharmacol. 58:253-262(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY RETICABINE.
[12]"Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels."
Wickenden A.D., Yu W., Zou A., Jegla T., Wagoner P.K.
Mol. Pharmacol. 58:591-600(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY RETICABINE.
[13]"The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells transfected with human KCNQ2/3 subunits."
Rundfeldt C., Netzer R.
Neurosci. Lett. 282:73-76(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVATION BY RETICABINE.
[14]"Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells."
Wickenden A.D., Zou A., Wagoner P.K., Jegla T.
Br. J. Pharmacol. 132:381-384(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION, ACTIVATION BY RETICABINE.
[15]"Identification by mass spectrometry and functional characterization of two phosphorylation sites of KCNQ2/KCNQ3 channels."
Surti T.S., Huang L., Jan Y.N., Jan L.Y., Cooper E.C.
Proc. Natl. Acad. Sci. U.S.A. 102:17828-17833(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-246, MUTAGENESIS OF THR-246.
[16]"A novel mutation of KCNQ3 (c.925T-->C) in a Japanese family with benign familial neonatal convulsions."
Hirose S., Zenri F., Akiyoshi H., Fukuma G., Iwata H., Inoue T., Yonetani M., Tsutsumi M., Muranaka H., Kurokawa T., Hanai T., Wada K., Kaneko S., Mitsudome A.
Ann. Neurol. 47:822-826(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT BFNS2 ARG-309.
[17]"KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum."
The BFNC physician consortium
Singh N.A., Westenskow P., Charlier C., Pappas C., Leslie J., Dillon J., Anderson V.E., Sanguinetti M.C., Leppert M.F.
Brain 126:2726-2737(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS BFNS2 GLY-305 AND VAL-310, CHARACTERIZATION OF VARIANT BFNS2 GLY-305, VARIANT SER-468, CHARACTERIZATION OF VARIANT SER-468.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF071491 expand/collapse EMBL AC list , AF071478, AF071479, AF071480, AF071481, AF071482, AF071483, AF071484, AF071485, AF071486, AF071487, AF071488, AF071489, AF071490 Genomic DNA. Translation: AAC96101.1.
AK296293 mRNA. Translation: BAG58996.1.
AC018540 Genomic DNA. No translation available.
AC123776 Genomic DNA. No translation available.
AC131042 Genomic DNA. No translation available.
AC136373 Genomic DNA. No translation available.
AF033347 mRNA. Translation: AAB97314.1.
RefSeqNP_001191753.1. NM_001204824.1.
NP_004510.1. NM_004519.3.
UniGeneHs.374023.

3D structure databases

ProteinModelPortalO43525.
SMRO43525. Positions 99-353, 509-534, 614-643.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109987. 2 interactions.
STRING9606.ENSP00000373648.

Chemistry

BindingDBO43525.
ChEMBLCHEMBL2221348.
GuidetoPHARMACOLOGY562.

Protein family/group databases

TCDB1.A.1.15.3. the voltage-gated ion channel (vic) superfamily.

PTM databases

PhosphoSiteO43525.

Proteomic databases

PaxDbO43525.
PRIDEO43525.

Protocols and materials databases

DNASU3786.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000388996; ENSP00000373648; ENSG00000184156. [O43525-1]
ENST00000521134; ENSP00000429799; ENSG00000184156. [O43525-2]
GeneID3786.
KEGGhsa:3786.
UCSCuc003ytj.3. human. [O43525-1]

Organism-specific databases

CTD3786.
GeneCardsGC08M133210.
HGNCHGNC:6297. KCNQ3.
HPAHPA035212.
MIM121201. phenotype.
602232. gene.
neXtProtNX_O43525.
Orphanet306. Benign familial infantile seizures.
1949. Benign familial neonatal seizures.
307. Juvenile myoclonic epilepsy.
PharmGKBPA30075.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1226.
HOGENOMHOG000220839.
HOVERGENHBG059014.
InParanoidO43525.
KOK04928.
OMAICAHSKE.
OrthoDBEOG73804Z.
TreeFamTF315186.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_13685. Neuronal System.

Gene expression databases

ArrayExpressO43525.
BgeeO43525.
CleanExHS_KCNQ3.
GenevestigatorO43525.

Family and domain databases

InterProIPR020969. Ankyrin-G_BS.
IPR005821. Ion_trans_dom.
IPR003091. K_chnl.
IPR003937. K_chnl_volt-dep_KCNQ.
IPR003948. K_chnl_volt-dep_KCNQ3.
IPR013821. K_chnl_volt-dep_KCNQ_C.
IPR028325. VG_K_chnl.
[Graphical view]
PANTHERPTHR11537. PTHR11537. 1 hit.
PTHR11537:SF5. PTHR11537:SF5. 1 hit.
PfamPF00520. Ion_trans. 1 hit.
PF03520. KCNQ_channel. 1 hit.
PF11956. KCNQC3-Ank-G_bd. 1 hit.
[Graphical view]
PRINTSPR00169. KCHANNEL.
PR01462. KCNQ3CHANNEL.
PR01459. KCNQCHANNEL.
ProtoNetSearch...

Other

ChiTaRSKCNQ3. human.
GeneWikiKvLQT3.
GenomeRNAi3786.
NextBio14871.
PROO43525.
SOURCESearch...

Entry information

Entry nameKCNQ3_HUMAN
AccessionPrimary (citable) accession number: O43525
Secondary accession number(s): B4DJY4, E7EQ89
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 15, 1999
Last modified: March 19, 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

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 8

Human chromosome 8: entries, gene names and cross-references to MIM