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1.A.1.15.2
    6 TMS voltage-gated K+ channel, KCNQ2 or Kv7.2.  Mutations cause benign familial neonatal convulsions (BNFC; epilepsy; Maljevic et al. 2016; Soldovieri et al. 2019).  It forms homotetramers or heterotetramers with KCNQ3/Kv7.3) (Soldovieri et al., 2006; Uehara et al., 2008)). Like all other Kv7.2 channels, it is activated by phosphatidyl inositol-4,5-bisphosphate and hence can be regulated by various neurotransmitters and hormones (Telezhkin et al. 2013).  Gating pore currents that go through the gating pores in TMSs1-4 (the voltage sensor) may give rise to peripheral nerve hyperexcitability (Moreau et al. 2014). 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). 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). The activities of Kv7 channels are modulated by polyunsaturated fatty acids (Larsson et al. 2020). Anticancer effects of FS48 from salivary glands of Xenopsylla cheopis via its blockage of voltage-gated K+ channels has been demonstrated (Xiong et al. 2023).

Accession Number:O43526
Protein Name:KCNQ2
Length:872
Molecular Weight:95848.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:6
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate potassium(1+)

Cross database links:

RefSeq: NP_004509.2    NP_742104.1    NP_742105.1    NP_742106.1    NP_742107.1   
Entrez Gene ID: 3785   
Pfam: PF00520    PF03520    PF11956   
OMIM: 121200  phenotype
602235  gene
KEGG: hsa:3785   

Gene Ontology

GO:0008076 C:voltage-gated potassium channel complex
GO:0005249 F:voltage-gated potassium channel activity
GO:0007399 P:nervous system development
GO:0006813 P:potassium ion transport
GO:0007268 P:synaptic transmission
GO:0055085 P:transmembrane transport

References (27)

[1] “Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles.”  Yokoyama M.et.al.   9039501
[2] “A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.”  Singh N.A.et.al.   9425895
[3] “A potassium channel mutation in neonatal human epilepsy.”  Biervert C.et.al.   9430594
[4] “KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel.”  Wang H.-S.et.al.   9836639
[5] “The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3.”  Tinel N.et.al.   9827540
[6] “Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.”  Yang W.-P.et.al.   9677360
[7] “Differential expression of KCNQ2 splice variants: implications to M current function during neuronal development.”  Smith J.S.et.al.   11160379
[8] “The DNA sequence and comparative analysis of human chromosome 20.”  Deloukas P.et.al.   11780052
[9] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[10] “Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy.”  Schroeder B.C.et.al.   9872318
[11] “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
[12] “M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit.”  Tinel N.et.al.   11034315
[13] “Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy.”  Schwake M.et.al.   10788442
[14] “Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current.”  Shapiro M.S.et.al.   10684873
[15] “Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors.”  Selyanko A.A.et.al.   10713961
[16] “Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine.”  Main M.J.et.al.   10908292
[17] “Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels.”  Wickenden A.D.et.al.   10953053
[18] “The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits.”  Rundfeldt C.et.al.   10713399
[19] “Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy.”  Cooper E.C.et.al.   10781098
[20] “An unappreciated role for RNA surveillance.”  Hillman R.T.et.al.   14759258
[21] “Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions.”  Biervert C.et.al.   10323247
[22] “Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor.”  Miraglia del Giudice E.et.al.   11175290
[23] “Myokymia and neonatal epilepsy caused by a mutation in the voltage sensor of the KCNQ2 K+ channel.”  Dedek K.et.al.   11572947
[24] “KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum.”  Singh N.A.et.al.   14534157
[25] “Neonatal convulsions and epileptic encephalopathy in an Italian family with a missense mutation in the fifth transmembrane region of KCNQ2.”  Dedek K.et.al.   12742592
[26] “Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.”  Wuttke T.V.et.al.   17872363
[27] “A novel mutation in KCNQ2 associated with BFNC, drug resistant epilepsy, and mental retardation.”  Borgatti R.et.al.   15249611
Structure:
5J03   6FEG   6FEH   7CR0   7CR1   7CR2   7CR3   7CR4   7CR7      [...more]

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MVQKSRNGGV YPGPSGEKKL KVGFVGLDPG APDSTRDGAL LIAGSEAPKR GSILSKPRAG 
61:	GAGAGKPPKR NAFYRKLQNF LYNVLERPRG WAFIYHAYVF LLVFSCLVLS VFSTIKEYEK 
121:	SSEGALYILE IVTIVVFGVE YFVRIWAAGC CCRYRGWRGR LKFARKPFCV IDIMVLIASI 
181:	AVLAAGSQGN VFATSALRSL RFLQILRMIR MDRRGGTWKL LGSVVYAHSK ELVTAWYIGF 
241:	LCLILASFLV YLAEKGENDH FDTYADALWW GLITLTTIGY GDKYPQTWNG RLLAATFTLI 
301:	GVSFFALPAG ILGSGFALKV QEQHRQKHFE KRRNPAAGLI QSAWRFYATN LSRTDLHSTW 
361:	QYYERTVTVP MYSSQTQTYG ASRLIPPLNQ LELLRNLKSK SGLAFRKDPP PEPSPSKGSP 
421:	CRGPLCGCCP GRSSQKVSLK DRVFSSPRGV AAKGKGSPQA QTVRRSPSAD QSLEDSPSKV 
481:	PKSWSFGDRS RARQAFRIKG AASRQNSEEA SLPGEDIVDD KSCPCEFVTE DLTPGLKVSI 
541:	RAVCVMRFLV SKRKFKESLR PYDVMDVIEQ YSAGHLDMLS RIKSLQSRVD QIVGRGPAIT 
601:	DKDRTKGPAE AELPEDPSMM GRLGKVEKQV LSMEKKLDFL VNIYMQRMGI PPTETEAYFG 
661:	AKEPEPAPPY HSPEDSREHV DRHGCIVKIV RSSSSTGQKN FSAPPAAPPV QCPPSTSWQP 
721:	QSHPRQGHGT SPVGDHGSLV RIPPPPAHER SLSAYGGGNR ASMEFLRQED TPGCRPPEGN 
781:	LRDSDTSISI PSVDHEELER SFSGFSISQS KENLDALNSC YAAVAPCAKV RPYIAEGESD 
841:	TDSDLCTPCG PPPRSATGEG PFGDVGWAGP RK