KCNQ4
entrez
9132
canonical
uniprot
P56696
canonical
ensembl
ENSG00000117013
resolver
ensp
ENSP00000262916
resolver
ensp
ENSP00000423756
resolver
ensp
ENSP00000712472
resolver
genesymbol
KCNQ4
resolver
hgnc
HGNC:6298
resolver
uniprot
B3KQH8
resolver
uniprot
O96025
resolver
uniprot_entry
B3KQH8_HUMAN
resolver
uniprot_entry
KCNQ4_HUMAN
resolver
uniprot_sec
O96025
resolver
activity_regulation
ACTIVITY REGULATION: Two molecules of phosphatidylinositol-4,5-bisphosphate (PIP2-I and PIP2-II) are essential to activate KCNQ4 channel by inducing the coupling of the voltage-sensing domain (VSD) and the pore-forming domain (PD). Upon channel activation, PIP2-I and PIP2-II disrupt the VSD-calmodulin/CALM interaction, causing the release of CALM from the VSD which triggers the opening of the gate (PubMed:34767770). Calcium suppresses KCNQ4 channel current through calcium-bound CALM C-terminus (PubMed:29429937). Therefore CALM acts as calcium sensor that controls channel activity (PubMed:29429937). ML213 potentiates KCNQ4 channel (PubMed:34767770). KCNQ4 channel is blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect (PubMed:10025409, PubMed:11245603). Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors (PubMed:10713961). {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10713961, ECO:0000269|PubMed:11245603, ECO:0000269|PubMed:29429937, ECO:0000269|PubMed:34767770}.
uniprot
proteins
amino_acid_sequence
MAEAPPRRLGLGPPPGDAPRAELVALTAVQSEQGEAGGGGSPRRLGLLGSPLPPGAPLPGPGSGSGSACGQRSSAAHKRYRRLQNWVYNVLERPRGWAFVYHVFIFLLVFSCLVLSVLSTIQEHQELANECLLILEFVMIVVFGLEYIVRVWSAGCCCRYRGWQGRFRFARKPFCVIDFIVFVASVAVIAAGTQGNIFATSALRSMRFLQILRMVRMDRRGGTWKLLGSVVYAHSKELITAWYIGFLVLIFASFLVYLAEKDANSDFSSYADSLWWGTITLTTIGYGDKTPHTWLGRVLAAGFALLGISFFALPAGILGSGFALKVQEQHRQKHFEKRRMPAANLIQAAWRLYSTDMSRAYLTATWYYYDSILPSFRELALLFEHVQRARNGGLRPLEVRRAPVPDGAPSRYPPVATCHRPGSTSFCPGESSRMGIKDRIRMGSSQRRTGPSKQHLAPPTMPTSPSSEQVGEATSPTKVQKSWSFNDRTRFRASLRLKPRTSAEDAPSEEVAEEKSYQCELTVDDIMPAVKTVIRSIRILKFLVAKRKFKETLRPYDVKDVIEQYSAGHLDMLGRIKSLQTRVDQIVGRGPGDRKAREKGDKGPSDAEVVDEISMMGRVVKVEKQVQSIEHKLDLLLGFYSRCLRSGTSASLGAVQVPLFDPDITSDYHSPVDHEDISVSAQTLSISRSVSTNMD
uniprot
proteins
disease_involvement
DISEASE: Deafness, autosomal dominant, 2A (DFNA2A) [MIM:600101]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:10571947, ECO:0000269|PubMed:10925378, ECO:0000269|PubMed:21242547}. 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) channel involved in the regulation of sensory cells excitability in the cochlea (PubMed:10025409, PubMed:34767770). KCNQ4/Kv7.4 channel is composed of 4 pore-forming subunits assembled as tetramers (PubMed:34767770). Promotes the outflow of potassium ions in the repolarization phase of action potential which plays a role in regulating membrane potential of excitable cells (PubMed:10025409, PubMed:11245603, PubMed:34767770). The channel conducts a slowly activating and deactivating current (PubMed:10025409, PubMed:11245603). Current often shows some inward rectification at positive potentials (PubMed:10025409). Channel may be selectively permeable in vitro to other cations besides potassium, in decreasing order of affinity K(+) = Rb(+) > Cs(+) > Na(+) (PubMed:10025409). Important for normal physiological function of inner ear such as sensory perception of sound (PubMed:10025409, PubMed:10369879). {ECO:0000269|PubMed:10025409, ECO:0000269|PubMed:10369879, ECO:0000269|PubMed:11245603, ECO:0000269|PubMed:34767770}.
uniprot
proteins
mass_dalton
77101
uniprot
proteins
mutagenesis
MUTAGEN 93; /note="R->A: Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type. No difference in current density."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 95; /note="R->A: Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type. No difference in current density."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 123; /note="E->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 124; /note="H->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 125; /note="Q->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 126; /note="E->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 194; /note="Q->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 196; /note="N->Q: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 205; /note="S->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 210; /note="Q->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 213; /note="R->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 216; /note="R->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 220; /note="R->A: Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type. No difference in current density."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 225; /note="K->A: Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type. No difference in current density."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 236; /note="K->A: Loss of detectable current."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 261; /note="K->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 262; /note="D->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 266; /note="D->G: Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 268; /note="S->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 272; /note="D->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 288; /note="D->G: Resistant to inhibition by potassium channel toxin SsTX. Normal voltage activation."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 290; /note="T->V: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 292; /note="H->G: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 295; /note="L->V: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 298; /note="V->T: No effect on inhibition by potassium channel toxin SsTX."; /evidence="ECO:0000269|PubMed:29358396"; MUTAGEN 330; /note="H->A: Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type; when associated with A-333. Decreased current density; when associated with A-333."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 333; /note="K->A: Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type. No difference in current density. Shifted activation curve of KCNQ4 toward positive potentials compared to wild-type; when associated with A-330. Decreased current density; when associated with A-330."; /evidence="ECO:0000269|PubMed:34767770"; MUTAGEN 346; /note="I->A: Loss of CALM binding. Impaired location at plasma membrane. Decreased KCNQ4 channel current."; /evidence="ECO:0000269|PubMed:29429937"; MUTAGEN 346; /note="I->D: Loss of CALM binding. Impaired location at plasma membrane. Loss of KCNQ4 channel current."; /evidence="ECO:0000269|PubMed:29429937"; MUTAGEN 536; /note="S->A: No difference in CALM binding compared to wild-type; when associated with A-540."; /evidence="ECO:0000269|PubMed:29429937"; MUTAGEN 536; /note="S->D: Loss of CALM binding; when associated with D-540. Loss of location at plasma membrane; when associated with D-540. Loss of KCNQ4 channel current; when associated with D-540."; /evidence="ECO:0000269|PubMed:29429937"; MUTAGEN 540; /note="L->A: No difference in CALM binding compared to wild-type; when associated with A-536."; /evidence="ECO:0000269|PubMed:29429937"; MUTAGEN 540; /note="L->D: Loss of CALM binding; when associated with D-536. Loss of location at plasma membrane; when associated with D-536. Loss of KCNQ4 channel current; when associated with D-536."; /evidence="ECO:0000269|PubMed:29429937
uniprot
proteins
protein_family
KQT (TC 1.A.1.15) subfamily
uniprot
proteins
protein_family
Kv7.4/KCNQ4 sub-subfamily
uniprot
proteins
protein_family
Potassium channel family
uniprot
proteins
pubmed
10025409
uniprot
proteins
pubmed
10369879
uniprot
proteins
pubmed
10571947
uniprot
proteins
pubmed
10713961
uniprot
proteins
pubmed
10925378
uniprot
proteins
pubmed
11245603
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17329207
uniprot
proteins
pubmed
21242547
uniprot
proteins
pubmed
23431407
uniprot
proteins
pubmed
29358396
uniprot
proteins
pubmed
29429937
uniprot
proteins
pubmed
34767770
uniprot
proteins
sequence_length
695
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Basal cell membrane {ECO:0000250|UniProtKB:Q9JK96}; Multi-pass membrane protein {ECO:0000269|PubMed:34767770}. Note=Situated at the basal membrane of cochlear outer hair cells. {ECO:0000250|UniProtKB:Q9JK96}.
uniprot
proteins
transmembrane_region
TRANSMEM 97..118; /note="Helical; Name=Segment S1"; /evidence="ECO:0000269|PubMed:34767770, ECO:0007744|PDB:7VNP"; TRANSMEM 130..152; /note="Helical; Name=Segment S2"; /evidence="ECO:0000269|PubMed:34767770, ECO:0007744|PDB:7VNP"; TRANSMEM 169..191; /note="Helical; Name=Segment S3"; /evidence="ECO:0000269|PubMed:34767770, ECO:0007744|PDB:7VNP"; TRANSMEM 203..223; /note="Helical; Voltage-sensor; Name=Segment S4"; /evidence="ECO:0000269|PubMed:34767770, ECO:0007744|PDB:7VNP"; TRANSMEM 236..258; /note="Helical; Name=Segment S5"; /evidence="ECO:0000269|PubMed:34767770, ECO:0007744|PDB:7VNP"; TRANSMEM 294..322; /note="Helical; Name=Segment S6"; /evidence="ECO:0000269|PubMed:34767770, ECO:0007744|PDB:7VNP
uniprot
proteins