INDRA statements for KCNQ4

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Statements

databases
phosphosite cbn pc11 biopax bel_lc signor biogrid lincs_drug tas hprd trrust ctd virhostnet phosphoelm drugbank omnipath | geneways tees isi trips rlimsp medscan sparser eidos reach
reading
HSP90beta affects KCNQ4
| 13
HSP90beta increases the amount of KCNQ4.
| 11
Modified HSP90beta increases the amount of KCNQ4. 6 / 6
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"Overexpression of HSP90beta increased cell surface expression of the WT KCNQ4 channel by 26 +/- 10.93% (XREF_FIG A)."
23750663
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"Over-expression of HSP90beta increased cell surface expression of the WT KCNQ4 channel by 26 +/- 10.93% (XREF_FIG)."
23750663
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"Over-expression of HSP90beta significantly increased surface expression of WT KCNQ4 channels (26 +/- 10.93%), while over-expression of HSP40 and HSP70 had no effect (XREF_FIG)."
23431407
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"Cell surface expression of the KCNQ4 channel in HEK293T cells mimicking heterozygous conditions of two DFNA2 mutations, L274H and W276S, could be restored by overexpression of HSP90beta XREF_BIBR."
23750663
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"Then, we tested whether cell surface expression of the KCNQ4 channel could be restored by HSP90beta overexpression in HEK293T cells mimicking the heterozygous condition of DFNA2 patients."
23750663
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"In both cases, Western blot showed that KCNQ4 surface expression could be restored to the WT level by HSP90beta over-expression (XREF_FIG)."
23431407
HSP90beta increases the amount of KCNQ4. 2 / 2
| 2
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"In a recent analysis of chaperones, knockdown and overexpression showed that HSP90beta, HSC70 and DNAJA1 enhance KCNQ4 levels, consistent with increased folding; however, HSP90alpha diminished KCNQ4 levels (XREF_TABLE)."
24609033
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"KCNQ4 surface expression was restored by HSP90beta in cells mimicking heterozygous conditions of the DFNA2 patients, even though it was not sufficient to rescue the function of KCNQ4 channels."
23431407
Modified HSP90beta increases the amount of KCNQ4-G321S. 1 / 1
| 1
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"Most importantly, overexpression of HSP90beta, a key component of the molecular chaperone network that controls the KCNQ4 biogenesis, significantly increased cell surface expression of the KCNQ4 mutants L281S, G296S and G321S."
23750663
Modified HSP90beta increases the amount of KCNQ4-G296S. 1 / 1
| 1
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"Most importantly, overexpression of HSP90beta, a key component of the molecular chaperone network that controls the KCNQ4 biogenesis, significantly increased cell surface expression of the KCNQ4 mutants L281S, G296S and G321S."
23750663
Modified HSP90beta increases the amount of KCNQ4-L281S. 1 / 1
| 1
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"Most importantly, overexpression of HSP90beta, a key component of the molecular chaperone network that controls the KCNQ4 biogenesis, significantly increased cell surface expression of the KCNQ4 mutants L281S, G296S and G321S."
23750663
HSP90beta activates KCNQ4.
| 2
HSP90beta activates KCNQ4. 2 / 2
| 2
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"In addition, HSP90beta increased the number of active WT KCNQ4 channels at the cell surface, and slightly that of WT and L274H mixed channels; the number of active WT and W276S mixed channels was not improved."
24609033
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"While overexpression of HSP90beta promotes KCNQ4 biogenesis, overexpression of HSP90alpha facilitates ubiquitin dependent degradation of the channel."
23750663
Ezogabine affects KCNQ4
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Ezogabine activates KCNQ4. 8 / 8
| 8
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"Also, both BMS-204352 and retigabine potentiated the voltage activated KCNQ4 current at all potentials tested."
11378159
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"Application of 10 muM retigabine increased the KCNQ4 current amplitude from 0.7 nA to 2.5 nA."
11378159
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"KCNQ4 channel activation by BMS-204352 and retigabine."
11378159
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"Here we show that KCNQ4 channels, stably expressed in HEK293 cells, were activated by retigabine and BMS-204352 in a reversible and concentration dependent manner in the concentration range 0.1-10 microM."
11378159
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"In this study we found an EC 50 value of 1.4 muM (at -30 mV) for retigabine activation of KCNQ4 channels."
11378159
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"We here demonstrate that BMS-204352 as well as retigabine activate KCNQ4 channels expressed in HEK293 cells.The HEK293 cell line stably expressing KCNQ4 channels is described by Sogaard et al. (2000)."
11378159
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"The KCNQ4 current was concentration-dependently and reversibly increased by BMS-204352 and retigabine in the concentration range 0.1-10 muM."
11378159
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"In the other experiment shown, retigabine (10 muM) increased the KCNQ4 current at -30 mV from 2.5 nA to 5.7 nA, and at -60 mV from 0.2 nA to 1.3 nA, lower panel)."
11378159
KCNQ4 affects potassium(1+)
| 1 6
KCNQ4 inhibits potassium(1+).
| 3
KCNQ4 inhibits potassium(1+). 2 / 2
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"Molecular modeling analysis suggested that the p.Ser269del mutation could cause structural distortion and change in the electrostatic surface potential of the KCNQ4 channel protein, which may impede K+ transport."
23399560
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"18 Surface channel expression studies in Xenopus oocytes suggest that missense mutations in the P-loop of KCNQ4 reduce potassium currents in a dominant negative manner."
21242547
KCNQ4-G285S inhibits potassium(1+). 1 / 1
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"Kubisch and colleagues have shown that the G285S mutation of KCNQ4 lies in the conserved channel pore region in exon 6 and abolishes ~ 90% of the potassium current of wild type KCNQ4 in the Xenopus oocyte system, reflecting a strong dominant negative effect."
19494570
KCNQ4 activates potassium(1+).
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KCNQ4 activates potassium(1+). 2 / 2
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"Kcne1, Kcnq1, and Kcnq4 encode subunits of inward rectifier voltage activated potassium channels."
23044516
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"OHC survival critically depends on a specific K+ conductance (I (K, n)) mediated by KCNQ4 (Kv7.4) channels."
20935082
Mutated KCNQ4 activates potassium(1+). 1 / 1
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"XREF_BIBR Further studies have suggested that mutation of KCNQ4 may cause chronic K+ overload, causing slow degeneration of outer hair cells, therefore explaining the progressive nature of DFNA2 hearing loss."
23776385
KCNQ4 binds potassium(1+).
| 1
Potassium(1+) binds Voltage_gated_ion_channels and KCNQ4. 1 / 1
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sparser
"Its cDNA encodes a polypeptide of 695 amino acids that forms a voltage-gated potassium Kv7.4 channel protein."
28340560
BDNF affects KCNQ4
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BDNF increases the amount of KCNQ4.
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BDNF increases the amount of KCNQ4. 5 / 5
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"BDNF profoundly increases KCNQ4 expression in comparison to other subtypes."
23089626
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"BDNF significantly and specifically increased expression of the KCNQ4 potassium channel subtype in comparison to control and NT-3 treated cells (9-fold for BDNF versus 1.6-fold for NT-3, p < 0.001, ANOVA) (XREF_FIG)."
23089626
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"Both BDNF and NT-3 increased KCNQ4 expression in cells following Neurog1-induction, with BDNF producing the most pronounced effect (XREF_FIG)."
23089626
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"BDNF increases neuronal KCNQ4 expression at the protein level."
23089626
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"BDNF profoundly and specifically increases KCNQ4 expression in neurons derived from embryonic stem cells."
23089626
BDNF activates KCNQ4.
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BDNF activates KCNQ4. 1 / 1
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"The novel observation of a BDNF selective increase in KCNQ4 in the present study suggests a link between high concentrations of this neurotrophin in the cochlear base with high expression levels of the KCNQ4 channel in the same region."
23089626
SsTx affects KCNQ4
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SsTx binds KCNQ4.
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KCNQ4 binds SsTx. 3 / 3
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"To further validate interactions between the positively charged residues on SsTx and the negatively charged residues of KCNQ4, we applied thermodynamic mutant cycle analysis to experimentally investigate the molecular interactions between SsTx and KCNQ4 (XREF_FIG, Top)."
29358396
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"We therefore first investigated the interaction between SsTx and KCNQ4."
29358396
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"These mutant toxins preserved WT like structural features, suggesting that the reduced inhibition is caused by a direct interaction between SsTx and KCNQ4."
29358396
SsTx inhibits KCNQ4.
| 2
SsTx inhibits KCNQ4. 2 / 2
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"Given that KCNQ4 is important in the regulation of pulmonary vascular tone, and blocking KCNQ4 increases the isometric tension of interlobular arteries, we hypothesized that SsTx may contribute to the vasospasm by inhibiting the KCNQ4 channel as reported in clinical cases of centipede envenomation."
29358396
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"In addition, the Hill slope is 1.18 +/- 0.03 for inhibition of KCNQ4 by SsTx (XREF_FIG), and thus multiple SsTx molecules could interact with positive synergy to inhibit the channel."
29358396
STUB1 affects KCNQ4
2 | 1 1
STUB1 binds KCNQ4.
2 | 1
STUB1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
HSPA binds STUB1 and KCNQ4. 1 / 1
| 1
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"These data suggested that Ang II reduced K v 7.4:HSP90 interactions thus enhancing protein ubiquitination via an increased interaction of Kv7.4:HSP70 complex with CHIP."
29686000
STUB1 inhibits KCNQ4.
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STUB1 inhibits mutated KCNQ4. 1 / 1
| 1
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"Mutant KCNQ4 is degraded by CHIP and protected by the HSP40-HSP70-HOP-HSP90 (AB1 and AA1) pathway."
26358502
HSPA8 affects KCNQ4
2 | 2
HSPA8 increases the amount of KCNQ4.
| 2
Modified HSPA8 increases the amount of KCNQ4. 1 / 1
| 1
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"Over-expression of DjA1 or HSC70 considerably increased total KCNQ4 level; while siRNA knockdown of these chaperones significantly reduced total KCNQ4 level (XREF_FIG, C. D. E. and F.)."
23431407
HSPA8 increases the amount of KCNQ4. 1 / 1
| 1
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"In a recent analysis of chaperones, knockdown and overexpression showed that HSP90beta, HSC70 and DNAJA1 enhance KCNQ4 levels, consistent with increased folding; however, HSP90alpha diminished KCNQ4 levels (XREF_TABLE)."
24609033
HSPA8 binds KCNQ4.
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HSPA8 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
CALM affects KCNQ4
| 2 2
CALM inhibits KCNQ4.
| 2
CALM inhibits KCNQ4. 2 / 2
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"Coexpression of CaM in Chinese hamster ovary (CHO) cells strongly reduced currents of KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3."
15901836
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"Moreover, overexpression of CaM reduced current amplitudes of KCNQ2, KCNQ4, and KCNQ5, but not those of KCNQ1 and KCNQ3."
23087646
CALM binds KCNQ4.
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CALM binds AOPEP and KCNQ4. 1 / 1
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"Together, these data support the idea that Apo/CaM:Kv7.4 interactions are essential for proper trafficking and are reminiscent of effects reported for mutations that disrupt the interaction between CaM and Kv7.1 ( Ghosh et al., 2006; Shamgar et al., 2006 ), Kv7.2 ( Etxeberria et al., 2008 ), and the Kv7.2/Kv7.3 heteromeric channel ( Liu and Devaux, 2014 )."
29429937
CALM binds AOPEP, KCNQ4, and ab. 1 / 1
| 1
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"Because we expect that the Apo/CaM clamp should represent the channel basal state, we made a set of structure-based mutations to probe the effects of interfering with Apo/CaM:Kv7.4 AB domain interactions."
29429937
Pyraclofos affects KCNQ4
| 3
Pyraclofos activates KCNQ4. 3 / 3
| 3
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"DFNA2 is a progressive deafness caused by mutations in the voltage activated potassium channel KCNQ4."
31102762
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"Also, both BMS-204352 and retigabine potentiated the voltage activated KCNQ4 current at all potentials tested."
11378159
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"In addition, mutations at both positions did not affect voltage activation of KCNQ4, suggesting that these residues directly affect SsTx-KCNQ4 interaction."
29358396
SGK1 affects KCNQ4
| 1 3
SGK1 activates KCNQ4. 3 / 3
| 1 3
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"Coexpression of wild type SGK1 but not coexpression of the inactive mutant (K127N) SGK1 significantly increased current amplitudes (by 67%) and significantly increased the resting potential of KCNQ4 expressing oocytes."
16301825
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"SGK1 activates a wide variety of ion channels (e.g., ENaC, SCN5A, TRPV4-6, ROMK, Kv1.3, Kv1.5, Kv4.3, KCNE1 and KCNQ1, KCNQ4, ASIC1, GluR6, ClCKa and barttin, ClC2, CFTR, and Orai and STIM), which participate in the regulation of transport, hormone release, neuroexcitability, inflammation, cell proliferation, and apoptosis."
23012321
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"Similarly, substitution of the putative phosphorylation site S444 in the K + channel KCNQ4 with Ala or Asp abolished Sgk1 modulation of KCNQ4."
25817867
N-ethylmaleimide affects KCNQ4
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N-ethylmaleimide activates KCNQ4. 2 / 2
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sparser
"Among these, NEM activates the isothiocyanate-activated cation channel TRPA1 [ xref ] and the voltage-gated K + channels (M channels) Kv7.2, Kv7.4, and Kv7.5 [ xref ] (also activated by H 2 O 2 in a dithiothreitol-reversible manner [ xref ])."
23481459
sparser
"The M-type current was activated by 1) 10 μM retigabine, an opener of all KCNQ channels except KCNQ1, 2) 10 μM zinc pyrithione, which augments all KCNQ channels except KCNQ3, and 3) 50 μM N-ethylmaleimide, which activates KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3, channels."
22135213
N-ethylmaleimide activates KCNQ4. 1 / 1
| 1
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"The M-type current was activated by 1) 10 muM retigabine, an opener of all KCNQ channels except KCNQ1, 2) 10 muM zinc pyrithione, which augments all KCNQ channels except KCNQ3, and 3) 50 muM N-ethylmaleimide, which activates KCNQ2, KCNQ4, and KCNQ5, but not KCNQ1 or KCNQ3, channels."
22135213
KCNQ4 affects SsTx
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KCNQ4 binds SsTx. 3 / 3
| 3
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"To further validate interactions between the positively charged residues on SsTx and the negatively charged residues of KCNQ4, we applied thermodynamic mutant cycle analysis to experimentally investigate the molecular interactions between SsTx and KCNQ4 (XREF_FIG, Top)."
29358396
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"We therefore first investigated the interaction between SsTx and KCNQ4."
29358396
reach
"These mutant toxins preserved WT like structural features, suggesting that the reduced inhibition is caused by a direct interaction between SsTx and KCNQ4."
29358396
KCNQ4 affects STUB1
2 | 1
STUB1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
HSPA binds STUB1 and KCNQ4. 1 / 1
| 1
sparser
"These data suggested that Ang II reduced K v 7.4:HSP90 interactions thus enhancing protein ubiquitination via an increased interaction of Kv7.4:HSP70 complex with CHIP."
29686000
KCNQ4 affects MAP6
| 3
KCNQ4 activates mutated MAP6. 3 / 3
| 3
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"The p.W241X mutation identified in this study is the first reported DFNA2 causing stop mutation in KCNQ4."
18941426
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"The latter is the first DFNA2 causing stop mutation reported in KCNQ4."
18941426
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"The latter is the first DFNA2 causing stop mutation reported in KCNQ4."
18941426
DNAJA1 affects KCNQ4
2 | 1
DNAJA1 binds KCNQ4.
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DNAJA1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
DNAJA1 increases the amount of KCNQ4.
| 1
DNAJA1 increases the amount of KCNQ4. 1 / 1
| 1
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"In a recent analysis of chaperones, knockdown and overexpression showed that HSP90beta, HSC70 and DNAJA1 enhance KCNQ4 levels, consistent with increased folding; however, HSP90alpha diminished KCNQ4 levels (XREF_TABLE)."
24609033
DFNA2 mutations affects KCNQ4
| 3
DFNA2 mutations-G321S inhibits KCNQ4. 1 / 1
| 1
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"Little or no increase in the average current densities after restoration of KCNQ4 surface expression indicates that the DFNA2 mutations L281S, G296S or G321S disrupt the conductance of the KCNQ4 channel."
23750663
DFNA2 mutations-G296S inhibits KCNQ4. 1 / 1
| 1
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"Little or no increase in the average current densities after restoration of KCNQ4 surface expression indicates that the DFNA2 mutations L281S, G296S or G321S disrupt the conductance of the KCNQ4 channel."
23750663
DFNA2 mutations-L281S inhibits KCNQ4. 1 / 1
| 1
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"Little or no increase in the average current densities after restoration of KCNQ4 surface expression indicates that the DFNA2 mutations L281S, G296S or G321S disrupt the conductance of the KCNQ4 channel."
23750663
Diclofenac affects KCNQ4
| 2
Diclofenac activates KCNQ4. 2 / 2
| 2
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"Diclofenac (100 muM) inhibited KCNQ5 channels, reducing maximum conductance by 53%, but increased maximum conductance of KCNQ4 channels by 38%."
20876743
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"Finally, diclofenac, which activates KCNQ2/3 and KCNQ4 channels but inhibits KCNQ5 channels, inhibited the M-type current in the majority of RPE cells but activated it in others."
22135213
STIP1 affects KCNQ4
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STIP1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
KCNQ4 affects calcium(2+)
| 2
KCNQ4 binds calcium(2+).
| 1
Calcium(2+) binds KCNQ4. 1 / 1
| 1
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"A number of in vitro biochemical studies have reported that Ca 2 + / CaM binds the B helices of KCNQ2, KCNQ3, and KCNQ4 (Alaimo et al., 2013; Xu et al., 2013)."
24333508
KCNQ4 activates calcium(2+).
| 1
KCNQ4 activates calcium(2+). 1 / 1
| 1
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"Similarly, KCNQ4 and KCNQ5 are key modulators of L-type Ca 2+ channel activity in cardiovascular cells [XREF_BIBR]."
24555524
KCNQ4 affects STIP1
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STIP1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
KCNQ4 affects HSPA8
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HSPA8 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
KCNQ4 affects HSP90B1
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HSP90B1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
KCNQ4 affects HSP90AA1
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HSP90AA1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
KCNQ4 affects GK
| 2
KCNQ4 inhibits GK.
| 1
KCNQ4-G285S inhibits GK. 1 / 1
| 1
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"Furthermore, the G285S mutation of KCNQ4 abolished G K, n in both of the knock-in mouse line [XREF_BIBR] and the transfected hair cell culture in vitro [XREF_BIBR]."
18797286
KCNQ4 activates GK.
| 1
KCNQ4 activates GK. 1 / 1
| 1
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"By using adenoviral delivery of KCNQ4 channels carrying G285S, Holt JR and colleagues demonstrated that KCNQ4 channels contributed to the M like conductances : G K, n of the cochlear outer hair cells and G K, L of the vestibular type I hair cells XREF_BIBR."
25116015
KCNQ4 affects DNAJA1
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DNAJA1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
KCNQ4 affects DIRAS3
| 1 1
KCNQ4 binds DIRAS3. 2 / 2
| 1 1
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"To investigate the association of KCNQ4 with ARHI, Van Eyken et al. examined KCNQ4 and detected a significant association between KCNQ4 and ARHI in two independent Caucasian populations."
25116015
sparser
"To investigate the association of KCNQ4 with ARHI, Van Eyken et al. examined KCNQ4 and detected a significant association between KCNQ4 and ARHI in two independent Caucasian populations."
25116015
KCNQ4 affects ADNSHL
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KCNQ4 activates ADNSHL. 2 / 2
| 2
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"In a recent study with 287 probands from independent Japanese ADNSHL families, Naito et al., found four missense mutations (p.Val230Glu, p.Pro291Ser, p.Pro291Leu and p.Arg291Leu), and concluded that KCNQ4 is a common cause of ADNSHL with a frequency of 6.62% in Japanese population [3]."
28802383
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"Since then, several subsequent studies have identified a total of 13 KCNQ4 gene mutations that have been suggested to cause ADNSHL."
20832469
KCNE5 affects KCNQ4
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KCNE5 inhibits KCNQ4. 2 / 2
| 2
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"KCNE5 was reported to inhibit KCNQ4 activity by ~ 65% in CHO cells (Angelo et al., 2002) but no effects were observed in oocytes (Strutz-Seebohm et al., 2006)."
27484720
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"KCNE5 was reported to inhibit KCNQ4 activity by ~ 65% in CHO cells 54 but no effects were observed in oocytes 58."
27484720
KCNE4S affects KCNQ4
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KCNE4S activates KCNQ4. 2 / 2
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"Human KCNE4S was found to augment KCNQ4 activity, in HEK cells and in Xenopus oocytes (although others found no effects for KCNE4S in oocytes or CHO cells (Grunnet et al., 2002; Vanoye et al., 2009); interestingly, human KCNE4L appears to lack this ability, at least when assayed in oocytes (Abbott, 2016b)."
27484720
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"Human KCNE4S was found to augment KCNQ4 activity, in HEK cells and in Xenopus oocytes; interestingly, human KCNE4L appears to lack this ability, at least when assayed in oocytes 42."
27484720
JAK2 affects KCNQ4
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JAK2 inhibits KCNQ4. 2 / 2
| 2
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"In conclusion, JAK2 downregulates KCNQ4 activity and thus counteracts K (+) exit, an effect which may contribute to cell volume regulation."
23543186
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"Downregulation of KCNQ4 by Janus kinase 2."
23543186
HSP90alpha affects KCNQ4
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HSP90alpha decreases the amount of KCNQ4. 1 / 1
| 1
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"In a recent analysis of chaperones, knockdown and overexpression showed that HSP90beta, HSC70 and DNAJA1 enhance KCNQ4 levels, consistent with increased folding; however, HSP90alpha diminished KCNQ4 levels (XREF_TABLE)."
24609033
Modified HSP90alpha decreases the amount of KCNQ4. 1 / 1
| 1
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"Consistent with these results, over-expression of HSP90beta increased; whereas up-regulation of HSP90alpha expression decreased total KCNQ4 level (XREF_FIG, C. and D.)."
23431407
HSP90B1 affects KCNQ4
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HSP90B1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
HSP90AB1 affects KCNQ4
| 1 1
HSP90AB1 increases the amount of KCNQ4.
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Modified HSP90AB1 increases the amount of KCNQ4. 1 / 1
| 1
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"Inducible HSP90AA1 and the constitutive HSP90AB1, had opposite effects on the cellular level of the KCNQ4 channel : HSP90AB1 over-expression partially restored KCNQ4 surface expression in cells mimicking heterozygous conditions in deafness patients."
26358502
HSP90AB1 binds KCNQ4.
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HSP90AB1 binds KCNQ4. 1 / 1
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sparser
"Western blot showed that both HSP90α and HSP90β co-precipitated with KCNQ4 proteins; conversely, KCNQ4 proteins were detected in HSP90α and HSP90β immunoprecipitates ( xref , A. and B.), which confirmed that HSP90α and HSP90β physically interact with KCNQ4 proteins."
23431407
HSP90AA1 affects KCNQ4
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HSP90AA1 binds KCNQ4. 2 / 2
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biogrid
No evidence text available
23431407
biogrid
No evidence text available
23431407
HSP90 affects KCNQ4
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HSP90 increases the amount of KCNQ4. 1 / 1
| 1
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"Rescue of KCNQ4 surface expression by HSP90."
23750663
Modified HSP90 increases the amount of KCNQ4. 1 / 1
| 1
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"Therefore, our data confirmed that decreased cell surface expression and impaired conductance of the KCNQ4 channel are two independent mechanisms underlying hearing loss in DFNA2; that restoration of KCNQ4 surface expression by overexpression of HSP90 was not sufficient to rescue the channel function in HEK293T cells mimicking the heterozygous condition of DFNA2 patients."
23750663
DIRAS3 affects KCNQ4
| 1 1
KCNQ4 binds DIRAS3. 2 / 2
| 1 1
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"To investigate the association of KCNQ4 with ARHI, Van Eyken et al. examined KCNQ4 and detected a significant association between KCNQ4 and ARHI in two independent Caucasian populations."
25116015
sparser
"To investigate the association of KCNQ4 with ARHI, Van Eyken et al. examined KCNQ4 and detected a significant association between KCNQ4 and ARHI in two independent Caucasian populations."
25116015
ARSD affects COL11A1, GJB6, KATNAL2, KCNQ4, MYH14, STXBP1, THRA, and UBE3A
| 2
STXBP1 binds THRA, UBE3A, COL11A1, MYH14, KATNAL2, GJB6, KCNQ4, and ARSD. 2 / 2
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sparser
"One such study, by Yuen et al., found genetic aberrations in STXBP1 , UBE3A , KATNAL2 , THRA , KCNQ4 , MYH14 , GJB6 and COL11A1 , some of which have been previously associated with ASD and some with overlapping conditions such as hearing loss [ xref ]."
28420080
sparser
"Mutations in different genes, such as STXBP1, KCNQ4, MYH14, GJB6, COL11A1, UBE3A, KATNAL2, and THRA, have also been associated with ASD [ xref ]."
31744938
5-HT affects KCNQ4
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5-HT activates KCNQ4. 2 / 2
| 2
sparser
"Furthermore, we demonstrate that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4."
29311835
sparser
"We hypothesize that the cellular redox signaling mechanism is involved in this 5-HT activation of Kv7.4."
29311835
Ztz240 affects KCNQ4
| 1
Ztz240 activates KCNQ4. 1 / 1
| 1
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"Ztz240, another KCNQ activator that is distinct from retigabine and ZnPy, potentiates KCNQ2 and KCNQ4 but does not affect KCNQ1 and KCNQ3."
23251633
Voltage-gated potassium channel affects KCNQ4
| 1
KCNQ4 binds voltage-gated potassium channel. 1 / 1
| 1
sparser
"In addition, mutations in the KCNQ4 voltage-gated potassium channel gene are associated with deafness [6] and deletion or inhibition of Kv1.1 in mice leads to epilepsy [7] or impairment of associative memory [8] ."
12586386
Voltage-clamp affects KCNQ4
| 1
Voltage-clamp activates KCNQ4. 1 / 1
| 1
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"Two-electrode voltage-clamp electrophysiology revealed that, when coexpressed in Xenopus laevis oocytes with various potassium channels, the newly discovered segment preserved conversion of KCNQ1 by hKCNE3 to a constitutively open channel, but prevented its inhibition of Kv4.2 and KCNQ4."
27162025
Thraa affects KCNQ4
| 1
Thraa decreases the amount of KCNQ4. 1 / 1
| 1
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"It has been shown recently that TH enhances the expression of the motor protein prestin via liganded TH receptor beta (TRbeta) while in contrast the expression of the potassium channel KCNQ4 is repressed by unliganded TRalpha1."
17520268
Salicylic acid affects KCNQ4
| 1
Salicylic acid inhibits KCNQ4. 1 / 1
| 1
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"Salicylate induced hearing loss is believed to arise from a reduction in the electromotile response of outer hair cells (OHCs) and/or reduction of KCNQ4 potassium currents in OHCs, which decreases the driving force for the transduction current."
25904892
Phosphatidylinositol phosphate affects KCNQ4
| 1
Phosphatidylinositol phosphate activates KCNQ4. 1 / 1
| 1
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"KCNQ1 and KCNE1, KCNQ4, and KCNQ5 channels are also reactivated by PIP 2 after inhibition by polylysine, showing that all KCNQ family members are PIP 2 sensitive."
22787448
Parvalbumin affects KCNQ4
| 1
KCNQ4 binds parvalbumin. 1 / 1
| 1
sparser
"This was judged on the basis of expression of OHC marker proteins such as the outward-rectifying potassium channel KCNQ4 (Fig.  xref ) or the Ca 2+ -binding protein parvalbumin (Fig.  xref )."
26476841
MiR153 affects KCNQ4
| 1
MiR153 activates KCNQ4. 1 / 1
| 1
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"It should be emphasized that miR153 induced KCNQ4 down-regulation is only a contributory component in the multifactorial disease of hypertension."
27389411
MV step affects KCNQ4
| 1
MV step activates KCNQ4. 1 / 1
| 1
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"As shown in Fig. 2 A, the KCNQ4 channels were closed at the -100 mV step and activated by the +10 mV step."
15980171
GacH affects KCNQ4
| 1
GacH activates KCNQ4. 1 / 1
| 1
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"The KCNQ4 gene, which encodes a potassium channel expressed in outer hair cells, underlies DFNA2 and was tested as a candidate gene for age related hearing impairment (ARHI) in two independent human populations."
19236853
Dlc affects KCNQ4
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KCNQ4 binds dlc. 1 / 1
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sparser
"211delC mutation in the KCNQ4 gene was associated with high-frequency SNHL in this family."
24655070
Calcium(2+) affects KCNQ4
| 1
Calcium(2+) binds KCNQ4. 1 / 1
| 1
reach
"A number of in vitro biochemical studies have reported that Ca 2 + / CaM binds the B helices of KCNQ2, KCNQ3, and KCNQ4 (Alaimo et al., 2013; Xu et al., 2013)."
24333508
Bepridil affects KCNQ4
| 1 1
Bepridil inhibits KCNQ4. 1 / 1
| 1 1
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"The antiarrhythmic KCNQ1 channel blocker bepridil inhibited KCNQ4 with an IC (50) value of 9.4 microM, whereas clofilium was without significant effect at 100 microM."
11245603
XE-991 affects KCNQ4
| 1
XE-991 inhibits KCNQ4. 1 / 1
| 1
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"The extracellular solution was complemented with 0.5 microM of apamin (Latoxan, Valence, France) and 0.2 microM of XE-991 (Tocris Bioscience, Lille, France) to block SK channels and KCNQ4 channels, respectively."
26568308
VCL affects KCNQ4
| 1
VCL inhibits KCNQ4. 1 / 1
| 1
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"The especially large potentiation of the steady-state current at potentials of -60 to -50 mV (about 4-fold increase) further adds to the functional effects of the compounds.The M-current blockers, linopirdine and XE 991, inhibited KCNQ2, KCNQ4, KCNQ2/Q3 and KCNQ3/Q4 channels with similar IC 50 values."
11378159
TRalpha1 aporeceptors affects KCNQ4
| 1
TRalpha1 aporeceptors decreases the amount of KCNQ4. 1 / 1
| 1
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"Simultaneously Kcnq4 expression was activated in the same cells by derepression of TRalpha1 aporeceptors mediated by an identified THresponse element, which modulates KCNQ4 promoter activity."
16803873
TEA affects KCNQ4
| 1
TEA inhibits KCNQ4. 1 / 1
| 1
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"On the other hand, the TEA block of KCNQ1 and KCNQ4 has a Hill slope of ~ 2 (Hadley et al., 2000), implying a different mechanism of block.The putative cognitive enhancer linopirdine and its more potent analogue 10,10-bis (4-pyridinylmethyl)-9(10H)-anthracenone (XE991) have been used as pharmacological markers of the KCNQ currents (Wang, H.-S."
11448722
SLC26A5 affects KCNQ4
| 1
KCNQ4 binds SLC26A5. 1 / 1
| 1
sparser
"Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4 , both of which are associated with voltage motility during the cochlear amplification of signals."
22761589
SLC25A10 affects KCNQ4
| 1
SLC25A10 activates KCNQ4. 1 / 1
| 1
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"Again, in excised patches KCNQ4 channel activity can be restored by application of diC 8 -PI (4,5) P 2 [XREF_BIBR, XREF_BIBR]."
25241941
POU1F1 affects KCNQ4
| 1
POU1F1 inhibits KCNQ4. 1 / 1
| 1
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"Pou1f1 dw/dw mutant mice have reduced immunohistochemical staining and function of KCNQ4 in OHCs."
22143287
NTF3 affects KCNQ4
| 1
NTF3 increases the amount of KCNQ4. 1 / 1
| 1
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"Both BDNF and NT-3 increased KCNQ4 expression in cells following Neurog1-induction, with BDNF producing the most pronounced effect (XREF_FIG)."
23089626
MicroRNA-153 affects KCNQ4
| 1
MicroRNA-153 activates KCNQ4. 1 / 1
| 1
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"MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension."
27389411
MiRP2 affects KCNQ4
| 1
MiRP2 inhibits KCNQ4. 1 / 1
| 1
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"KCNQ4 also bears a serine at a position equivalent to KCNQ1-S338 in the S6 but is inhibited by MiRP2."
17227916
Kcnq4/5 affects KCNQ4
| 1
Kcnq4/5 activates KCNQ4. 1 / 1
| 1
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"This branching pattern can be explained by two duplication events in the vertebrate lineage, where a single proto-orthologue to Kcnq2/3/4/5, duplicated to create two ancestor genes to Kcnq2/3 and Kcnq4/5 which both duplicated again to produce Kcnq2, kcnq3, kcnq4 and kcnq5 genes as conserved in current vertebrate genomes."
19200367
Kcnq2/3 affects KCNQ4
| 1
Kcnq2/3 activates KCNQ4. 1 / 1
| 1
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"This branching pattern can be explained by two duplication events in the vertebrate lineage, where a single proto-orthologue to Kcnq2/3/4/5, duplicated to create two ancestor genes to Kcnq2/3 and Kcnq4/5 which both duplicated again to produce Kcnq2, kcnq3, kcnq4 and kcnq5 genes as conserved in current vertebrate genomes."
19200367
KCNQ4 affects voltage-gated potassium channel
| 1
KCNQ4 binds voltage-gated potassium channel. 1 / 1
| 1
sparser
"In addition, mutations in the KCNQ4 voltage-gated potassium channel gene are associated with deafness [6] and deletion or inhibition of Kv1.1 in mice leads to epilepsy [7] or impairment of associative memory [8] ."
12586386
KCNQ4 affects transport
| 1
KCNQ4 inhibits transport. 1 / 1
| 1
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"Molecular modeling analysis suggested that the p.Ser269del mutation could cause structural distortion and change in the electrostatic surface potential of the KCNQ4 channel protein, which may impede K+ transport."
23399560
KCNQ4 affects pyrithione
| 1
KCNQ4 activates pyrithione. 1 / 1
| 1
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"Interestingly, the channel activity of the p.Leu47Pro KCNQ4 protein was rescued by the KCNQ activators MaxiPost and zinc pyrithione."
30556268
KCNQ4 affects pyraclofos
| 1
KCNQ4 activates pyraclofos. 1 / 1
| 1
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"Moreover, while linopirdine sensitive KCNQ4 currents mediated most of the voltage gated current in apical OHCs (77.3 +/-3.2%, n = 12), both linopirdine sensitive KCNQ4 channels and IBTX sensitive BK channels contributed to voltage gated currents in basal OHCs (XREF_FIG)."
21079807
KCNQ4 affects parvalbumin
| 1
KCNQ4 binds parvalbumin. 1 / 1
| 1
sparser
"This was judged on the basis of expression of OHC marker proteins such as the outward-rectifying potassium channel KCNQ4 (Fig.  xref ) or the Ca 2+ -binding protein parvalbumin (Fig.  xref )."
26476841
KCNQ4 affects dominant negative DFNA2 mutation
| 1
KCNQ4 activates dominant negative DFNA2 mutation. 1 / 1
| 1
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"We now generated mice in which the KCNQ4 gene was disrupted or carried a dominant negative DFNA2 mutation."
16437162
KCNQ4 affects dlc
| 1
KCNQ4 binds dlc. 1 / 1
| 1
sparser
"211delC mutation in the KCNQ4 gene was associated with high-frequency SNHL in this family."
24655070
KCNQ4 affects cell death
| 1
KCNQ4 activates cell death. 1 / 1
| 1
reach
"One proposed etiology of hearing loss is outer hair cell death caused by KCNQ4 deficiency."
29093664
KCNQ4 affects Voltage_gated_ion_channels, and potassium(1+)
| 1
Potassium(1+) binds Voltage_gated_ion_channels and KCNQ4. 1 / 1
| 1
sparser
"Its cDNA encodes a polypeptide of 695 amino acids that forms a voltage-gated potassium Kv7.4 channel protein."
28340560
KCNQ4 affects SLC26A5
| 1
KCNQ4 binds SLC26A5. 1 / 1
| 1
sparser
"Previous genetic studies have documented parallel evolution of nucleotide sequences in Prestin and KCNQ4 , both of which are associated with voltage motility during the cochlear amplification of signals."
22761589
KCNQ4 affects SGK1
| 1
KCNQ4 inhibits SGK1. 1 / 1
| 1
reach
"Similarly, substitution of the putative phosphorylation site S444 in the K + channel KCNQ4 with Ala or Asp abolished Sgk1 modulation of KCNQ4."
25817867
KCNQ4 affects RABGAP1L
| 1
Mutated KCNQ4 activates RABGAP1L. 1 / 1
| 1
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"Therefore, it was proposed that Kcnq4 mutations induce a progressive HHL due to chronic depolarization of OHC, leading to their degeneration [XREF_BIBR]."
22567353
KCNQ4 affects LIPC
| 1
KCNQ4 activates LIPC. 1 / 1
| 1
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"Conversely, screening of 80 hearing impaired families did not result in the identification of a single mutation in KCNQ4 causing HL (Talebizadeh et al., 1999)."
15276679
KCNQ4 affects KCNQ2/3
| 1
KCNQ4 activates KCNQ2/3. 1 / 1
| 1
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"However, KCNQ4 and KCNQ1 homomers produce a K + current with an amplitude that is dramatically larger than those of KCNQ2 and KCNQ3 homomers, and KCNQ2/3 heteromers (9-12)."
22713565
KCNQ4 affects KCNE subunits
| 1
KCNQ4 binds KCNE subunits. 1 / 1
| 1
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"Strutz-Seebohm and colleagues investigated functional interactions between KCNE subunits and KCNQ4 expressed in Xenopus oocytes and found that all KCNEs modulated KCNQ4 voltage dependence, protein stability, or ion selectivity."
24416770
KCNQ4 affects KCNE isoforms
| 1
KCNQ4 binds KCNE isoforms. 1 / 1
| 1
reach
"Interestingly, all KCNE isoforms can also associate with KCNQ4 and interactions with KCNE4 in particular can augment the K + current [XREF_BIBR]."
20132415
KCNQ4 affects IK
| 1
Mutated KCNQ4 inhibits IK. 1 / 1
| 1
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"Since the resting potential of OHC is dependent on potassium currents, KCNQ4 mutation can reduce I K, which leads to selective degeneration of OHCs."
25904892
KCNQ4 affects HSP90AB1
| 1
HSP90AB1 binds KCNQ4. 1 / 1
| 1
sparser
"Western blot showed that both HSP90α and HSP90β co-precipitated with KCNQ4 proteins; conversely, KCNQ4 proteins were detected in HSP90α and HSP90β immunoprecipitates ( xref , A. and B.), which confirmed that HSP90α and HSP90β physically interact with KCNQ4 proteins."
23431407
KCNQ4 affects GYG1
| 1
Mutated KCNQ4 inhibits GYG1. 1 / 1
| 1
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"XREF_BIBR Another missense mutation, G287A, identified by Arnett et al in an American family was also found to disrupt the GYG sequence just as in the initial reported KCNQ4 mutation."
23776385
KCNQ4 affects DNFA2
| 1
KCNQ4 activates DNFA2. 1 / 1
| 1
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"This interval contains a known deafness gene, KCNQ4, which underlies DNFA2 deafness."
21242547
KCNQ4 affects Chaperones
| 1
KCNQ4 binds Chaperones. 1 / 1
| 1
sparser
"Identification of Molecular Chaperones Associated with KCNQ4 Channels."
23431407
KCNQ4 affects CDH
| 1
KCNQ4 activates CDH. 1 / 1
| 1
reach
"We hypothesized that KCNQ1, KCNQ4, and KCNQ5 expression is altered in the pulmonary vasculature of nitrofen induced CDH rats."
28189443
KCNQ4 affects ARSD
| 1
KCNQ4 binds ARSD. 1 / 1
| 1
reach
"One such study, by Yuen et al., found genetic aberrations in STXBP1, UBE3A, KATNAL2, THRA, KCNQ4, MYH14, GJB6 and COL11A1, some of which have been previously associated with ASD and some with overlapping conditions such as hearing loss [XREF_BIBR]."
28420080
KCNQ3 affects KCNQ4, KCNQ5, and SRC
| 1
SRC binds KCNQ3, KCNQ4, and KCNQ5. 1 / 1
| 1
sparser
"Immunoprecipitation and immunoblot analysis showed Src-dependent phosphotyrosine signals associated with KCNQ3, KCNQ4, and KCNQ5 but not with KCNQ1 or KCNQ2 that may be tyrosine phosphorylation of the channel subunits."
12514204
KCNQ channel opener affects KCNQ4
| 1
KCNQ channel opener activates KCNQ4. 1 / 1
| 1
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"Zinc pyrithione (ZnPy) is a newly identified KCNQ channel opener, which potently activates KCNQ2, KCNQ4, and KCNQ5."
18490447
KCNE3S affects KCNQ4
| 1
KCNE3S inhibits KCNQ4. 1 / 1
| 1
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"KCNE3S inhibits KCNQ4 activity when expressed in Xenopus oocytes, whereas KCNE3L had no effect in similar experiments XREF_BIBR XREF_BIBR."
27922120
KCNE subunits affects KCNQ4
| 1
KCNQ4 binds KCNE subunits. 1 / 1
| 1
reach
"Strutz-Seebohm and colleagues investigated functional interactions between KCNE subunits and KCNQ4 expressed in Xenopus oocytes and found that all KCNEs modulated KCNQ4 voltage dependence, protein stability, or ion selectivity."
24416770
KCNE isoforms affects KCNQ4
| 1
KCNQ4 binds KCNE isoforms. 1 / 1
| 1
reach
"Interestingly, all KCNE isoforms can also associate with KCNQ4 and interactions with KCNE4 in particular can augment the K + current [XREF_BIBR]."
20132415
KCN affects KCNQ4
| 1
KCN activates KCNQ4. 1 / 1
| 1
reach
"Mutations in the potassium channel gene KCNQ4 underlie DFNA2, an autosomal dominant form of progressive hearing loss in humans."
10760300
HSPA affects KCNQ4, and STUB1
| 1
HSPA binds STUB1 and KCNQ4. 1 / 1
| 1
sparser
"These data suggested that Ang II reduced K v 7.4:HSP90 interactions thus enhancing protein ubiquitination via an increased interaction of Kv7.4:HSP70 complex with CHIP."
29686000
HSP90beta [ affects KCNQ4
| 1
Modified HSP90beta [ increases the amount of KCNQ4. 1 / 1
| 1
reach
"Cell surface expression of the KCNQ4 channel in HEK293T cells mimicking heterozygous conditions of two DFNA2 mutations, L274H and W276S, could be restored by overexpression of HSP90beta [XREF_BIBR]."
23750663
GJB6 affects KCNQ4
| 1
GJB6 activates KCNQ4. 1 / 1
| 1
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"Gjb2 and Gjb6 genes produce the gap junction proteins, connexin 26 (Cx26) and connexin 30 (Cx30), while Cldn14 codes for a tight-junction protein; Kcne1, Kcnq1, and Kcnq4, all encoding for potassium ion channels; and finally Slc26a4 that encodes an anion transporter."
22567353
GJB2 affects KCNQ4
| 1
GJB2 activates KCNQ4. 1 / 1
| 1
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"Gjb2 and Gjb6 genes produce the gap junction proteins, connexin 26 (Cx26) and connexin 30 (Cx30), while Cldn14 codes for a tight-junction protein; Kcne1, Kcnq1, and Kcnq4, all encoding for potassium ion channels; and finally Slc26a4 that encodes an anion transporter."
22567353
EZG affects KCNQ4
| 1
EZG activates KCNQ4. 1 / 1
| 1
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"XREF_BIBR However, KCNQ4 and KCNQ5 potassium channels are activated by EZG and may be found in cochlear hair cells XREF_BIBR or smooth muscle."
22888276
DjA1 affects KCNQ4
| 1
Modified DjA1 increases the amount of KCNQ4. 1 / 1
| 1
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"Over-expression of DjA1 or HSC70 considerably increased total KCNQ4 level; while siRNA knockdown of these chaperones significantly reduced total KCNQ4 level (XREF_FIG, C. D. E. and F.)."
23431407
D( affects KCNQ4
| 1
D( activates KCNQ4. 1 / 1
| 1
reach
"The KCNQ4 current was investigated in further detail and was increased by 19.9 +/-1.6% (n = 20) by D (2L) receptor stimulation."
12827359
Chaperones affects KCNQ4
| 1
KCNQ4 binds Chaperones. 1 / 1
| 1
sparser
"Identification of Molecular Chaperones Associated with KCNQ4 Channels."
23431407
CNTNAP1 affects KCNQ4
| 1
CNTNAP1 activates KCNQ4. 1 / 1
| 1
reach
"XREF_BIBR showed that Caspr1 is necessary for retention of KCNQ4 in the calyx membrane and for maintaining appropriate synaptic cleft width."
21734302
CNR1 affects KCNQ4
| 1 1
CNR1 inhibits KCNQ4. 1 / 1
| 1 1
sparser
"It was suggested that 2-AG might be an endogenous repressor of myoblast differentiation via CB 1 -mediated inhibition of Kv7.4 channels [ xref ]."
25796370
BMS-204352 affects KCNQ4
| 1
BMS-204352 activates KCNQ4. 1 / 1
| 1
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"We here demonstrate that BMS-204352 as well as retigabine activate KCNQ4 channels expressed in HEK293 cells.The HEK293 cell line stably expressing KCNQ4 channels is described by Sogaard et al. (2000)."
11378159
BBR affects KCNQ4
| 1
BBR activates KCNQ4. 1 / 1
| 1
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"At 10 muM, BBR potentiated KCNQ1, KCNQ4, and KCNQ5 but not KCNQ3."
25735002
ARSD affects KCNQ4
| 1
KCNQ4 binds ARSD. 1 / 1
| 1
reach
"One such study, by Yuen et al., found genetic aberrations in STXBP1, UBE3A, KATNAL2, THRA, KCNQ4, MYH14, GJB6 and COL11A1, some of which have been previously associated with ASD and some with overlapping conditions such as hearing loss [XREF_BIBR]."
28420080
AOPEP affects CALM, KCNQ4, and ab
| 1
CALM binds AOPEP, KCNQ4, and ab. 1 / 1
| 1
sparser
"Because we expect that the Apo/CaM clamp should represent the channel basal state, we made a set of structure-based mutations to probe the effects of interfering with Apo/CaM:Kv7.4 AB domain interactions."
29429937
AOPEP affects CALM, and KCNQ4
| 1
CALM binds AOPEP and KCNQ4. 1 / 1
| 1
sparser
"Together, these data support the idea that Apo/CaM:Kv7.4 interactions are essential for proper trafficking and are reminiscent of effects reported for mutations that disrupt the interaction between CaM and Kv7.1 ( Ghosh et al., 2006; Shamgar et al., 2006 ), Kv7.2 ( Etxeberria et al., 2008 ), and the Kv7.2/Kv7.3 heteromeric channel ( Liu and Devaux, 2014 )."
29429937
ACTG1 affects GJB3, KCNQ4, SERPINB6, and TMIE
| 1
ACTG1 binds TMIE, GJB3, KCNQ4, and SERPINB6. 1 / 1
| 1
sparser
"The del( GJB6 -D13S1830), SERPINB6 , TMIE , COCH , ESPN , ACTG1 , GJB3 , and KCNQ4 mutations were infrequently associated with deafness in the Moravian-Silesian population."
30344259