O43525 (KCNQ3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	872 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in KCNQ3 are the cause of benign familial neonatal seizures type 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. Ref.1 Ref.2 Ref.14 Ref.15
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]

Ontologies

Keywords
Biological process	Ion transport Potassium transport Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Epilepsy
Domain	Transmembrane Transmembrane helix
Ligand	Potassium
Molecular function	Ionic channel Potassium channel Voltage-gated channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome
Cellular component	voltage-gated potassium channel complex Traceable author statement. Source: ProtInc
Molecular function	voltage-gated potassium channel activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 872	872	Potassium voltage-gated channel subfamily KQT member 3		PRO_0000054034
Regions
	Transmembrane	122 – 142	21	Helical; Name=Segment S1; Potential
	Transmembrane	153 – 173	21	Helical; Name=Segment S2; Potential
	Transmembrane	197 – 217	21	Helical; Name=Segment S3; Potential
	Transmembrane	226 – 247	22	Helical; Voltage-sensor; Name=Segment S4; Potential
	Transmembrane	262 – 282	21	Helical; Name=Segment S5; Potential
	Intramembrane	304 – 324	21	Pore-forming; Name=Segment H5; Potential
	Transmembrane	331 – 351	21	Helical; Name=Segment S6; Potential
	Motif	316 – 321	6	Selectivity filter By similarity
	Compositional bias	13 – 24	12	Poly-Gly
Amino acid modifications
	Modified residue	598	1	Phosphoserine By similarity
	Modified residue	746	1	Phosphothreonine Ref.13
Natural variations
	Natural variant	305	1	D → G in BFNS2; reduces the maximal heteromeric current by approx. 40% with no alteration in voltage dependence of activation or deactivation kinetics. Ref.15		VAR_026994
	Natural variant	309	1	W → R in BFNS2. Ref.14		VAR_010935
	Natural variant	310	1	G → 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.2 Ref.15		VAR_001546
	Natural variant	414	1	E → G. Corresponds to variant rs2303995 [ dbSNP | Ensembl ].		VAR_053859
	Natural variant	468	1	N → S Has no statistically significant effect on the current or biophysical properties of the heteromeric channel. Ref.15		VAR_026995
Experimental info
	Mutagenesis	318	1	G → S: >50% Reduction of wt heteromeric current; ratio of 1:1 and 1:1:2. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O43525 [UniParc]. Last modified July 15, 1999. Version 2. Checksum: BB79C69EE8591A84	FASTA	872	96,742
	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

References

	« Hide 'large scale' referencesShow '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: 9872318] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], CHARACTERIZATION OF VARIANT BFNS2 VAL-310, MUTAGENESIS OF GLY-318. Tissue: Brain.
[2]	"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: 9425900] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 48-872, VARIANT BFNS2 VAL-310. Tissue: Brain.
[3]	"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: 9677360] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Brain and Fetal brain.
[4]	"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: 10479678] [Abstract] Cited for: INVOLVEMENT IN M-LIKE CURRENT.
[5]	"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: 11034315] [Abstract] Cited for: ASSOCIATION WITH KCNE2.
[6]	"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: 10788442] [Abstract] Cited for: SURFACE EXPRESSION OF HETEROMERS.
[7]	"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: 10684873] [Abstract] Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[8]	"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: 10713961] [Abstract] Cited for: INHIBITION BY M1 MUSCARINIC RECEPTORS.
[9]	"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: 10908292] [Abstract] Cited for: ACTIVATION BY RETICABINE.
[10]	"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: 10953053] [Abstract] Cited for: ACTIVATION BY RETICABINE.
[11]	"The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits." Rundfeldt C., Netzer R. Neurosci. Lett. 282:73-76(2000) [PubMed: 10713399] [Abstract] Cited for: ACTIVATION BY RETICABINE.
[12]	"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: 11159685] [Abstract] Cited for: CHARACTERIZATION, ACTIVATION BY RETICABINE.
[13]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-746, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"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: 10852552] [Abstract] Cited for: VARIANT BFNS2 ARG-309.
[15]	"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: 14534157] [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

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF071491 , AF071478, AF071479, AF071480, AF071481, AF071482, AF071483, AF071484, AF071485, AF071486, AF071487, AF071488, AF071489, AF071490 Genomic DNA. Translation: AAC96101.1. AF033347 mRNA. Translation: AAB97314.1.
IPI	IPI00012857.
RefSeq	NP_001191753.1. NM_001204824.1. NP_004510.1. NM_004519.3.
UniGene	Hs.374023. Hs.587442.
3D structure databases
ProteinModelPortal	O43525.
SMR	O43525. Positions 111-372, 614-643.
ModBase	Search...
Protein-protein interaction databases
STRING	O43525.
Protein family/group databases
TCDB	1.A.1.15.3. voltage-gated ion channel (VIC) superfamily.
PTM databases
PhosphoSite	O43525.
Proteomic databases
PRIDE	O43525.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000388996; ENSP00000373648; ENSG00000184156.
GeneID	3786.
KEGG	hsa:3786.
UCSC	uc003ytj.1. human.
Organism-specific databases
CTD	3786.
GeneCards	GC08M133210.
H-InvDB	HIX0201315.
HGNC	HGNC:6297. KCNQ3.
HPA	HPA035212.
MIM	121201. phenotype. 602232. gene.
neXtProt	NX_O43525.
Orphanet	1949. Benign familial neonatal seizures. 307. Juvenile myoclonic epilepsy.
PharmGKB	PA30075.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG714141.
HOVERGEN	HBG059014.
InParanoid	O43525.
OMA	TRIDMIF.
OrthoDB	EOG4V9TPZ.
PhylomeDB	O43525.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	O43525.
Bgee	O43525.
CleanEx	HS_KCNQ3.
Genevestigator	O43525.
GermOnline	ENSG00000184156. Homo sapiens.
Family and domain databases
InterPro	IPR020969. Ankyrin-G_BS. IPR005821. Ion_trans. IPR003091. K_chnl. IPR003937. K_chnl_volt-dep_KCNQ. IPR003948. K_chnl_volt-dep_KCNQ3. IPR013821. K_chnl_volt-dep_KCNQ_C. [Graphical view]
KO	K04928.
PANTHER	PTHR11537:SF5. KCNQ3_channel. 1 hit.
Pfam	PF00520. Ion_trans. 1 hit. PF03520. KCNQ_channel. 1 hit. PF11956. KCNQC3-Ank-G_bd. 1 hit. [Graphical view]
PRINTS	PR00169. KCHANNEL. PR01462. KCNQ3CHANNEL. PR01459. KCNQCHANNEL.
ProtoNet	Search...
Other
NextBio	14871.
SOURCE	Search...

Entry information

Entry name

KCNQ3_HUMAN

Accession

Primary (citable) accession number: O43525

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 15, 1999
Last modified:	January 25, 2012
This is version 114 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.