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1.A.1.15.3
6 TMS voltage-gated K+ channel, KCNQ3 or Kv7.3.  Mutations cause benign familial neonatal convulsions (BNFC; epilepsy; Maljevic et al. 2016). Forms homotetramers or heterotetramers with KCNQ2 (Soldovieri et al., 2006; Uehara et al., 2008).  Retigabine and ICA73, two anti-epileptic drugs, act via distinct mechanisms due to interactions with specific residues that underlie subtype specificity of KCNQ channel openers (Wang et al. 2016). Gabapentin at low concentrations is a activator of KCNQ3, KCNQ2/3 and KCNQ5 but not KCNQ2 or KCNQ4 (Manville and Abbott 2018). At high concentrations it can be inhibitory.  A  tight spatial and functional relationship between the DAT/GLT-1 transporters and the Kv7.2/7.3 potassium channel immediately readjusts the membrane potential of the neuron, probably to limit the neurotransmitter-mediated neuronal depolarization (Bartolomé-Martín et al. 2019). E-2-dodecenal from cilantro (Coriandrum sativum) is a potent activator and anticonvulsant that binds with an affinity of 60 nM to TMS5 in several KCNQ channels including KCNQ2 and 3 (Manville and Abbott 2019). Pathogenic variants in KCNQ2 and KCNQ3, paralogous genes encoding Kv7.2 and Kv7.3 voltage-gated K+ channel subunits, are responsible for early-onset developmental/epileptic disorders characterized by heterogeneous clinical phenotypes ranging from benign familial neonatal epilepsy (BFNE) to early-onset developmental and epileptic encephalopathy (DEE). KCNQ2 variants account for the majority of pedigrees with BFNE, and KCNQ3 variants are responsible for a much smaller subgroup (Miceli et al. 2020). The M240R variant mainly affects the voltage sensitivity, in contrast to previously analyzed BFNE Kv7.3 variants that reduce current density (Miceli et al. 2020).

Accession Number:O43525
Protein Name:KCNQ3
Length:872
Molecular Weight:96742.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate K+

Cross database links:

RefSeq: NP_004510.1   
Entrez Gene ID: 3786   
Pfam: PF00520    PF03520    PF11956   
OMIM: 121201  phenotype
602232  gene
KEGG: hsa:3786   

Gene Ontology

GO:0008076 C:voltage-gated potassium channel complex
GO:0005249 F:voltage-gated potassium channel activity
GO:0006813 P:potassium ion transport
GO:0007268 P:synaptic transmission
GO:0055085 P:transmembrane transport

References (15)

[1] “Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy.”  Schroeder B.C.et.al.   9872318
[2] “A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.”  Charlier C.et.al.   9425900
[3] “Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.”  Yang W.-P.et.al.   9677360
[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.et.al.   10479678
[5] “M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit.”  Tinel N.et.al.   11034315
[6] “Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.”  Schwake M.et.al.   10788442
[7] “Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current.”  Shapiro M.S.et.al.   10684873
[8] “Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors.”  Selyanko A.A.et.al.   10713961
[9] “Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.”  Main M.J.et.al.   10908292
[10] “Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels.”  Wickenden A.D.et.al.   10953053
[11] “The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits.”  Rundfeldt C.et.al.   10713399
[12] “Characterization of KCNQ5/Q3 potassium channels expressed in mammalian cells.”  Wickenden A.D.et.al.   11159685
[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.et.al.   17924679
[14] “A novel mutation of KCNQ3 (c.925T-->C) in a Japanese family with benign familial neonatal convulsions.”  Hirose S.et.al.   10852552
[15] “KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum.”  Singh N.A.et.al.   14534157
Structure:
5J03     

External Searches:

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MGLKARRAAG AAGGGGDGGG GGGGAANPAG GDAAAAGDEE RKVGLAPGDV EQVTLALGAG 
61:	ADKDGTLLLE GGGRDEGQRR TPQGIGLLAK TPLSRPVKRN NAKYRRIQTL IYDALERPRG 
121:	WALLYHALVF LIVLGCLILA VLTTFKEYET VSGDWLLLLE TFAIFIFGAE FALRIWAAGC 
181:	CCRYKGWRGR LKFARKPLCM LDIFVLIASV PVVAVGNQGN VLATSLRSLR FLQILRMLRM 
241:	DRRGGTWKLL GSAICAHSKE LITAWYIGFL TLILSSFLVY LVEKDVPEVD AQGEEMKEEF 
301:	ETYADALWWG LITLATIGYG DKTPKTWEGR LIAATFSLIG VSFFALPAGI LGSGLALKVQ 
361:	EQHRQKHFEK RRKPAAELIQ AAWRYYATNP NRIDLVATWR FYESVVSFPF FRKEQLEAAS 
421:	SQKLGLLDRV RLSNPRGSNT KGKLFTPLNV DAIEESPSKE PKPVGLNNKE RFRTAFRMKA 
481:	YAFWQSSEDA GTGDPMAEDR GYGNDFPIED MIPTLKAAIR AVRILQFRLY KKKFKETLRP 
541:	YDVKDVIEQY SAGHLDMLSR IKYLQTRIDM IFTPGPPSTP KHKKSQKGSA FTFPSQQSPR 
601:	NEPYVARPST SEIEDQSMMG KFVKVERQVQ DMGKKLDFLV DMHMQHMERL QVQVTEYYPT 
661:	KGTSSPAEAE KKEDNRYSDL KTIICNYSET GPPEPPYSFH QVTIDKVSPY GFFAHDPVNL 
721:	PRGGPSSGKV QATPPSSATT YVERPTVLPI LTLLDSRVSC HSQADLQGPY SDRISPRQRR 
781:	SITRDSDTPL SLMSVNHEEL ERSPSGFSIS QDRDDYVFGP NGGSSWMREK RYLAEGETDT 
841:	DTDPFTPSGS MPLSSTGDGI SDSVWTPSNK PI