KCNQ2
entrez
3785
canonical
uniprot
O43526
canonical
ensembl
ENSG00000075043
resolver
ensp
ENSP00000339611
resolver
ensp
ENSP00000345523
resolver
ensp
ENSP00000352035
resolver
ensp
ENSP00000353668
resolver
ensp
ENSP00000359244
resolver
ensp
ENSP00000486706
resolver
ensp
ENSP00000487469
resolver
ensp
ENSP00000516702
resolver
ensp
ENSP00000522218
resolver
enst
ENST00000627221
resolver
enst
ENST00000706989
resolver
genesymbol
KCNQ2
resolver
hgnc
HGNC:6296
resolver
uniprot
A0A0D9SGG3
resolver
uniprot
A0A9L9PXL0
resolver
uniprot
O43796
resolver
uniprot
O75580
resolver
uniprot
O95845
resolver
uniprot
Q4VXP4
resolver
uniprot
Q4VXR6
resolver
uniprot
Q53Y30
resolver
uniprot
Q5VYT8
resolver
uniprot
Q96J59
resolver
uniprot
Q99454
resolver
uniprot_entry
A0A0D9SGG3_HUMAN
resolver
uniprot_entry
A0A9L9PXL0_HUMAN
resolver
uniprot_entry
KCNQ2_HUMAN
resolver
uniprot_entry
Q53Y30_HUMAN
resolver
uniprot_sec
O43796
resolver
uniprot_sec
O75580
resolver
uniprot_sec
O95845
resolver
uniprot_sec
Q4VXP4
resolver
uniprot_sec
Q4VXR6
resolver
uniprot_sec
Q5VYT8
resolver
uniprot_sec
Q96J59
resolver
uniprot_sec
Q99454
resolver
activity_regulation
ACTIVITY REGULATION: Phosphatidylinositol-4,5-bisphosphate (PIP2) potentiates the activation of KCNQ channels by enhancing the electro-mechanical coupling of the voltage-sensing domain (VSD) and the pore-forming domain (PD) (PubMed:24277843, PubMed:37857637). In the closed state of the channel, PIP2 is anchored at the S2-S3 loop; upon channel activation, PIP2 interacts with the S4-S5 linker and is involved in channel gating (PubMed:24277843). Calcium suppresses KCNQ2 and KCNQ2-KCNQ3 channel currents, with calcium-bound calmodulin inducing a change in channel configuration which leads to the reduction of channel affinity for PIP2 and subsequent current suppression (By similarity). M-channel is blocked by linopirdine and XE991, and activated by the anticonvulsants ztz240 and retigabine (PubMed:10713399, PubMed:10908292, PubMed:10953053, PubMed:11572947, PubMed:12742592, PubMed:17872363, PubMed:32884139, PubMed:9836639). {ECO:0000250|UniProtKB:O88944, ECO:0000269|PubMed:10713399, ECO:0000269|PubMed:10908292, ECO:0000269|PubMed:10953053, ECO:0000269|PubMed:11572947, ECO:0000269|PubMed:12742592, ECO:0000269|PubMed:17872363, ECO:0000269|PubMed:24277843, ECO:0000269|PubMed:32884139, ECO:0000269|PubMed:37857637, ECO:0000269|PubMed:9836639}.
uniprot
proteins
amino_acid_sequence
MVQKSRNGGVYPGPSGEKKLKVGFVGLDPGAPDSTRDGALLIAGSEAPKRGSILSKPRAGGAGAGKPPKRNAFYRKLQNFLYNVLERPRGWAFIYHAYVFLLVFSCLVLSVFSTIKEYEKSSEGALYILEIVTIVVFGVEYFVRIWAAGCCCRYRGWRGRLKFARKPFCVIDIMVLIASIAVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLLGSVVYAHSKELVTAWYIGFLCLILASFLVYLAEKGENDHFDTYADALWWGLITLTTIGYGDKYPQTWNGRLLAATFTLIGVSFFALPAGILGSGFALKVQEQHRQKHFEKRRNPAAGLIQSAWRFYATNLSRTDLHSTWQYYERTVTVPMYSSQTQTYGASRLIPPLNQLELLRNLKSKSGLAFRKDPPPEPSPSKGSPCRGPLCGCCPGRSSQKVSLKDRVFSSPRGVAAKGKGSPQAQTVRRSPSADQSLEDSPSKVPKSWSFGDRSRARQAFRIKGAASRQNSEEASLPGEDIVDDKSCPCEFVTEDLTPGLKVSIRAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAGHLDMLSRIKSLQSRVDQIVGRGPAITDKDRTKGPAEAELPEDPSMMGRLGKVEKQVLSMEKKLDFLVNIYMQRMGIPPTETEAYFGAKEPEPAPPYHSPEDSREHVDRHGCIVKIVRSSSSTGQKNFSAPPAAPPVQCPPSTSWQPQSHPRQGHGTSPVGDHGSLVRIPPPPAHERSLSAYGGGNRASMEFLRQEDTPGCRPPEGNLRDSDTSISIPSVDHEELERSFSGFSISQSKENLDALNSCYAAVAPCAKVRPYIAEGESDTDSDLCTPCGPPPRSATGEGPFGDVGWAGPRK
uniprot
proteins
disease_involvement
DISEASE: Seizures, benign familial neonatal 1 (BFNS1) [MIM:121200]: 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. Some rare cases manifest an atypical severe phenotype associated with epileptic encephalopathy and psychomotor retardation. The disorder is distinguished from benign familial infantile seizures by an earlier age at onset. In some patients, neonatal convulsions are followed later in life by myokymia, a benign condition characterized by spontaneous involuntary contractions of skeletal muscles fiber groups that can be observed as vermiform movement of the overlying skin. Electromyography typically shows continuous motor unit activity with spontaneous oligo- and multiplet-discharges of high intraburst frequency (myokymic discharges). Some patients may have isolated myokymia. {ECO:0000269|PubMed:11175290, ECO:0000269|PubMed:11572947, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:15249611, ECO:0000269|PubMed:23360469, ECO:0000269|PubMed:25982755, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:9425895}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Developmental and epileptic encephalopathy 7 (DEE7) [MIM:613720]: An autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities. {ECO:0000269|PubMed:12742592, ECO:0000269|PubMed:15249611, ECO:0000269|PubMed:24463883, ECO:0000269|PubMed:25740509, ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:27864847}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Pore-forming subunit of the voltage-gated potassium (Kv) M-channel which is responsible for the M-current, a key controller of neuronal excitability (PubMed:24277843, PubMed:28793216, PubMed:9836639). M-channel is composed of pore-forming subunits KCNQ2 and KCNQ3 assembled as heterotetramers (PubMed:10781098, PubMed:14534157, PubMed:32884139, PubMed:37857637, PubMed:9836639). The native M-current has 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 (PubMed:14534157, PubMed:28793216, PubMed:9836639). KCNQ2-KCNQ3 M-channel is selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) > Rb(+) > Cs(+) > Na(+) (PubMed:28793216). M-channel association with SLC5A3/SMIT1 alters channel ion selectivity, increasing Na(+) and Cs(+) permeation relative to K(+) (PubMed:28793216). Suppressed by activation of the muscarinic acetylcholine receptor CHRM1 (PubMed:10684873, PubMed:10713961). {ECO:0000269|PubMed:10684873, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:10781098, ECO:0000269|PubMed:14534157, ECO:0000269|PubMed:24277843, ECO:0000269|PubMed:28793216, ECO:0000269|PubMed:32884139, ECO:0000269|PubMed:37857637, ECO:0000269|PubMed:9836639}.
uniprot
proteins
mass_dalton
95848
uniprot
proteins
mutagenesis
MUTAGEN 52; /note="S->E: 40% increase in potassium current amplitude. Ratio of 1:1."; /evidence="ECO:0000269|PubMed:9872318"; MUTAGEN 52; /note="S->Q: Decrease of PKA stimulation. Ratio of 1:1."; /evidence="ECO:0000269|PubMed:9872318"; MUTAGEN 87; /note="R->A: No change in voltage activation of KNCQ2 channel."; /evidence="ECO:0000269|PubMed:37857637"; MUTAGEN 89; /note="R->A: Increased voltage sensitivity of KNCQ2 channel."; /evidence="ECO:0000269|PubMed:37857637"; MUTAGEN 162; /note="K->A: Decreased current amplitude; reduced sensitivity to PIP2. Does not alter the voltage sensitivity of the channel."; /evidence="ECO:0000269|PubMed:24277843"; MUTAGEN 214; /note="R->A: No change in voltage activation of KNCQ2 channel."; /evidence="ECO:0000269|PubMed:37857637"; MUTAGEN 217; /note="T->D: Abolishes currents without reducing channel protein expression."; /evidence="ECO:0000269|PubMed:16319223"; MUTAGEN 230; /note="K->L: Reduced sensitivity to PIP2 and voltage sensitivity of KCNQ2 channel."; /evidence="ECO:0000269|PubMed:24277843"; MUTAGEN 279; /note="G->S: More than 50% reduction of wt heteromeric current. Ratio of 1:1 and 1:1:2."; /evidence="ECO:0000269|PubMed:9872318"; MUTAGEN 327; /note="K->A: Decreased voltage sensitivity of KNCQ2 channel. No difference in PIP2 sensitivity."; /evidence="ECO:0000269|PubMed:24277843, ECO:0000269|PubMed:37857637"; MUTAGEN 331; /note="K->A: No difference in PIP2 sensitivity."; /evidence="ECO:0000269|PubMed:24277843
uniprot
proteins
post_translational_modification
PTM: KCNQ2/KCNQ3 heteromeric current can be increased by intracellular cyclic AMP, an effect that depends on phosphorylation of Ser-52 in the N-terminal region. {ECO:0000269|PubMed:16319223, ECO:0000269|PubMed:9872318}.; PTM: KCNQ2/KCNQ3 are ubiquitinated by NEDD4L. Ubiquitination leads to protein degradation (Probable). Degradation induced by NEDD4L is inhibited by USP36 (PubMed:27445338). {ECO:0000269|PubMed:27445338, ECO:0000305|PubMed:27445338}.
uniprot
proteins
protein_family
KQT (TC 1.A.1.15) subfamily
uniprot
proteins
protein_family
Kv7.2/KCNQ2 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10323247
uniprot
proteins
pubmed
10479678
uniprot
proteins
pubmed
10684873
uniprot
proteins
pubmed
10713399
uniprot
proteins
pubmed
10713961
uniprot
proteins
pubmed
10781098
uniprot
proteins
pubmed
10788442
uniprot
proteins
pubmed
10908292
uniprot
proteins
pubmed
10953053
uniprot
proteins
pubmed
11034315
uniprot
proteins
pubmed
11160379
uniprot
proteins
pubmed
11175290
uniprot
proteins
pubmed
11572947
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
12742592
uniprot
proteins
pubmed
14534157
uniprot
proteins
pubmed
14759258
uniprot
proteins
pubmed
15249611
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16319223
uniprot
proteins
pubmed
17872363
uniprot
proteins
pubmed
23360469
uniprot
proteins
pubmed
24277843
uniprot
proteins
pubmed
24463883
uniprot
proteins
pubmed
25740509
uniprot
proteins
pubmed
25818041
uniprot
proteins
pubmed
25982755
uniprot
proteins
pubmed
26138355
uniprot
proteins
pubmed
26993267
uniprot
proteins
pubmed
27445338
uniprot
proteins
pubmed
27564677
uniprot
proteins
pubmed
27864847
uniprot
proteins
pubmed
28793216
uniprot
proteins
pubmed
32884139
uniprot
proteins
pubmed
37857637
uniprot
proteins
pubmed
9039501
uniprot
proteins
pubmed
9425895
uniprot
proteins
pubmed
9430594
uniprot
proteins
pubmed
9677360
uniprot
proteins
pubmed
9827540
uniprot
proteins
pubmed
9836639
uniprot
proteins
pubmed
9872318
uniprot
proteins
sequence_length
872
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10788442, ECO:0000269|PubMed:9836639}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 91..113; /note="Helical; Name=Segment S1"; /evidence="ECO:0000269|PubMed:32884139, ECO:0007744|PDB:7CR3"; TRANSMEM 124..145; /note="Helical; Name=Segment S2"; /evidence="ECO:0000269|PubMed:32884139, ECO:0007744|PDB:7CR3"; TRANSMEM 164..183; /note="Helical; Name=Segment S3"; /evidence="ECO:0000269|PubMed:32884139, ECO:0007744|PDB:7CR3"; TRANSMEM 197..215; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000269|PubMed:32884139, ECO:0007744|PDB:7CR3"; TRANSMEM 228..253; /note="Helical; Name=Segment S5"; /evidence="ECO:0000269|PubMed:32884139, ECO:0007744|PDB:7CR3"; TRANSMEM 288..314; /note="Helical; Name=Segment S6"; /evidence="ECO:0000269|PubMed:32884139, ECO:0007744|PDB:7CR3
uniprot
proteins