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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
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CALM affects KCNQ2
| 1 52 55
CALM binds KCNQ2.
| 1 52 37
| 1 42 35
reach
"These data are entirely consistent with the concept that CaM bound to KCNQ2 acts as a Ca2+ sensor, conferring Ca2+ dependence to the trafficking of the channel to the plasma membrane and fully explaining the requirement of CaM binding for KCNQ2 function."
reach
"Since CaM interaction with KCNQ2 is required for functional expression of KCNQ channels in non neuronal cells XREF_BIBR, XREF_BIBR, XREF_BIBR, we hypothesized that CaM regulates preferential targeting of KCNQ channels to the axonal surface."
sparser
"Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon."
sparser
"These results suggest that a change in the configuration of CaMKCNQ2 binding induced by elevated intracellular calcium led to the reduction in PIP2 affinity of the KCNQ2 channel."
reach
"After the KCNQ2 and CaM complex was purified by immunoprecipitation in calcium (-) condition, dissociation of CaM from KCNQ2 protein was examined by exposing KCNQ2-CaM resin to calcium (XREF_FIG)."
reach
"Since A-kinase-anchoring protein (AKAP) 79 XREF_BIBR, XREF_BIBR regulates CaM binding to KCNQ2 XREF_BIBR and serves as an adaptor protein for CaM and PKC XREF_BIBR, XREF_BIBR, the mechanism responsible for CaM mediated trafficking of KCNQ channels to the axonal surface may well converge with the ability of CaM to modulate PKC dependent inhibition of M-current via AKAP79/150 XREF_BIBR, XREF_BIBR and PIP 2 XREF_BIBR."
sparser
"To test whether CaM interaction with KCNQ2 regulates the targeting of CD4-Q2C to the axonal surface, we introduced point mutations in helix A of KCNQ2 including two BFNC mutations, L339R and R353G xref ( xref )."
sparser
"Here we show that the L339R mutation in helix A, which is linked to human benign neonatal convulsions, perturbs CaM binding to KCNQ2 channels and prevents their correct trafficking to the plasma membrane."
sparser
"These results together indicate that disruption of CaM interaction with KCNQ2 by the A343D mutation impairs the trafficking of HA-KCNQ3/KCNQ2 channels from the ER to the axon."
sparser
"To test whether CaM binding to KCNQ2 promotes trafficking of HA-KCNQ3/KCNQ2 channels from the ER to the axon, we performed pulse-chase experiments after removal of BFA."
sparser
"As suggested by secondary structure prediction, the mutation residue is likely to disrupt the amphipatic a-helical structure in helix B, which appears to be necessary for proper interaction of CaM with Kv7.2 [12–15,20,32] ."
sparser
"The R353G mutation located distal to the IQ motif ( xref ) has been shown to moderately reduce CaM binding to KCNQ2 in HEK293T cells xref , xref ."
sparser
"CaM binds simultaneously to two sites of Kv7.2 in a 1∶1 stoichiometry xref ; xref ."
sparser
"The current study suggests that not only the calcium-induced dissociation of CaM, but also a change in the configuration of CaM-KCNQ2 binding could suppress the KCNQ2 current."
sparser
"Moreover, binding of WT CaM to KCNQ2 can moderately reduce the constitutive current through KCNQ2 homomeric channels by changing channel structure ( xref )."
sparser
"These results support the hypothesis that changes in calcium levels alter KCNQ2-CaM binding, which leads to the suppression of the current."
sparser
"Both WT and dominant-negative CaM bind to the C terminus of KCNQ2 ( xref ) and (a) mutations in KCNQ2 that affect CaM binding, (b) expression of dominant-negative CaM, or (c) expression of a “CaM sponge” lead to retention of KCNQ2 homomeric channels in the ER ( xref ; xref ; xref )."
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"The second group found that both wt CaM and DN CaM interact with KCNQ2, consistent with our results that DN CaM can act as a dominant negative in CaM actions."
sparser
"The interaction of the Kv7.2 C-terminus with CaM was used as positive control."
sparser
"Since the KCNQ2(R353G) channel with impaired CaM binding and low PIP2 affinity xref showed a stronger response to ionomycin, it would be reasonable to assume that the KCNQ2-CaM interaction regulates PIP2 affinity of the KCNQ2 subunit as we reported previously xref ."
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"In contrast, the A343D mutation, which blocked CaM binding to KCNQ2 (XREF_FIG) XREF_BIBR, XREF_BIBR, abolished surface and intracellular expression of HA-KCNQ3 and KCNQ2 channels at the AIS and distal axons (XREF_FIG, XREF_FIG) and reduced the surface " Axon and Dendrite " ratio to below 1 (XREF_FIG)."
reach
"Recent studies have shown that calmodulin (CaM) binds to the KCNQ2 and KCNQ3 C termini and may function as an auxiliary channel subunit XREF_BIBR, XREF_BIBR, XREF_BIBR."
sparser
"CK2 phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating Ca 2+ gating of SK2 channels."
reach
"In addition, Ca 2 + / CaM binds the 1-5-10 motifs of both KCNQ2 and KCNQ3 with a low-affinity, and favours subunit interaction."
reach
"The structural elements critical for CaM binding to KCNQ2 lie in two conserved motifs in the proximal half of the channel C-terminal domain."
sparser
"CK2phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating SK2 channels."
reach
"Disruption of CaM binding to KCNQ2 impairs trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon."
reach
"To test whether CaM interaction with KCNQ2 regulates the targeting of CD4-Q2C to the axonal surface, we introduced point mutations in helix A of KCNQ2 including two BFNC mutations, L339R and R353G XREF_BIBR (XREF_FIG)."
reach
"CK2phosphorylated SK2 bound CaM but not KCNQ2 bound CaM, thereby selectively regulating SK2 channels."
sparser
"These results together suggest that disruption of CaM binding to KCNQ2 impairs the trafficking of CD4-Q2C proteins from the ER to the AIS and distal axons."
reach
"Despite a modest reduction of CaM binding to KCNQ2 by the R353G mutation (XREF_FIG) XREF_BIBR, XREF_BIBR, the R353G mutant channels were localized to the AIS and axonal surface to a similar extent as the wild-type channels (XREF_FIG)."
reach
"To test whether CaM binding to KCNQ2 promotes trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon, we performed pulse-chase experiments after removal of BFA."
reach
"Since the R353G mutation in KCNQ2 reduces CaM binding to heteromeric KCNQ2 and KCNQ3 channels only by 20% XREF_BIBR, XREF_BIBR, our results suggest that a greater degree of impairment in CaM binding to KCNQ2 is needed to prevent targeting of heteromeric channels to the axonal surface."
sparser
"These data are entirely consistent with the concept that CaM bound to KCNQ2 acts as a Ca2+ sensor, conferring Ca2+ dependence to the trafficking of the channel to the plasma membrane and fully explaining the requirement of CaM binding for KCNQ2 function."
reach
"Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2 and KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon."
sparser
"Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum."
sparser
"Our prediction thus supports these results by highlighting the importance of the interactions between KCNQ2 and the CaM proteins."
sparser
"Considering the modest effect of CaM1234 on the axonal surface expression of HA-KCNQ3/KCNQ2 channels ( xref ), CaM bound to KCNQ2 may act as a Ca 2+ sensor for modulating not only the M-current, but also the channel density at the axonal membrane."
sparser
"The process appears to require at least two steps; the first involves the transient association of CaM with KCNQ2, and in the second, the complex adopts an "active" conformation that is more stable and is that which confers the capacity to exit the endoplasmic reticulum."
sparser
"Although CaM can still interact with KCNQ3 subunits xref , xref , the A343D mutation, which abolished CaM binding to KCNQ2 ( xref ), prevented surface and intracellular expression of intact HA-KCNQ3/KCNQ2 channels at the AIS and distal axons ( xref – xref ), consistent with a recent study reporting altered neuronal distribution of heteromeric channels by the I340A mutation xref ."
reach
"Disruption of CaM binding to KCNQ2 inhibits enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface."
sparser
"In contrast, the BFNC R353G mutation located distal to the IQ motif modestly reduced but did not abolish CaM binding to KCNQ2 ( xref ) and had minimal effect on the polarized axonal surface expression of HA-KCNQ3/KCNQ2 channels ( xref )."
reach
"Given the importance that both groups ascribed to both of these regions for CaM binding to KCNQ2 subunits, we were surprised to find in the current work that IQ 2, but not IQ 1, produced a Ca 2+ -dependent gel shift of CaM."
reach
"In this study, we investigated the molecular mechanism of KCNQ2 current suppression mediated by calcium bound calmodulin."
reach
"In contrast, the BFNC R353G mutation located distal to the IQ motif modestly reduced but did not abolish CaM binding to KCNQ2 (XREF_FIG) and had minimal effect on the polarized axonal surface expression of HA-KCNQ3 and KCNQ2 channels (XREF_FIG)."
sparser
"We also demonstrated that a CaM deficient mutant channel, KCNQ2(R353G), showed augmented ionomycin-induced current suppression, which suggests that a change in the KCNQ2-CaM interaction is critical for the suppression."
sparser
"KCNQ2 subunit associates with another CaM binding protein as a constituent of the channel complex: AKAP79/150, a scaffold protein critical for KCNQ2 channel regulation xref , xref ."
reach
"The R353G mutation located distal to the IQ motif (XREF_FIG) has been shown to moderately reduce CaM binding to KCNQ2 in HEK293T cells XREF_BIBR, XREF_BIBR."
sparser
"The first CaM-binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2+-insensitive CaM mutant bind to KCNQ2."
reach
"The first CaM binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2 +-insensitive CaM mutant bind to KCNQ2."
reach
"Calmodulin bound to the KCNQ2 subunit regulates channel trafficking and stabilizes channel activity."
reach
"CK2 phosphorylated SK2 bound CaM but not KCNQ2 bound CaM, thereby selectively regulating Ca 2+ gating of SK2 channels."
reach
"Moreover, binding of WT CaM to KCNQ2 can moderately reduce the constitutive current through KCNQ2 homomeric channels by changing channel structure."
sparser
"Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum."
sparser
"Calmodulin bound to the KCNQ2 subunit regulates channel trafficking and stabilizes channel activity."
sparser
"The second group found that both wt CaM and DN CaM interact with KCNQ2, consistent with our results that DN CaM can act as a dominant negative in CaM actions."
reach
"Here, we have studied this functional interaction using fluorescence and NMR spectroscopy, in order to compare the association between Kv7.2 and full-length CaM 1-148 with that between Kv7.2 and the isolated N- (CaM 1-78) and C-domain (CaM 79-148) fragments XREF_BIBR."
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"Although CaM can still interact with KCNQ3 subunits XREF_BIBR, XREF_BIBR, the A343D mutation, which abolished CaM binding to KCNQ2 (XREF_FIG), prevented surface and intracellular expression of intact HA-KCNQ3 and KCNQ2 channels at the AIS and distal axons (XREF_FIG - XREF_FIG), consistent with a recent study reporting altered neuronal distribution of heteromeric channels by the I340A mutation XREF_BIBR."
sparser
"Since the R353G mutation in KCNQ2 reduces CaM binding to heteromeric KCNQ2/KCNQ3 channels only by 20% xref , xref , our results suggest that a greater degree of impairment in CaM binding to KCNQ2 is needed to prevent targeting of heteromeric channels to the axonal surface."
reach
"These results together indicate that disruption of CaM interaction with KCNQ2 by the A343D mutation impairs the trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon."
reach
"Although the binding of CaM with Kv7.2 is not fully recapitulated by its individual segments XREF_BIBR, this analysis helps in understanding how CaM interacts with the channel."
sparser
"Given the importance that both groups ascribed to both of these regions for CaM binding to KCNQ2 subunits, we were surprised to find in the current work that IQ 2 , but not IQ 1 , produced a Ca 2+ -dependent gel shift of CaM."
reach
"Here we show that the L339R mutation in helix A, which is linked to human benign neonatal convulsions, perturbs CaM binding to KCNQ2 channels and prevents their correct trafficking to the plasma membrane."
reach
"These results together suggest that disruption of CaM binding to KCNQ2 impairs the trafficking of CD4-Q2C proteins from the ER to the AIS and distal axons."
reach
"First, we introduced two mutations within the IQ domain of KCNQ3 : an isoleucine to alanine substitution at the position 342 (KCNQ3-I342A); and an alanine substitution of the residues 346 to 349 (KCNQ3-WRYY; Fig. 1 A) which are also involved in the binding of CaM to KCNQ2 and Nav1.2 channels (Feldkamp et al., 2012; Wen and Levitan, 2002)."
sparser
"Despite a modest reduction of CaM binding to KCNQ2 by the R353G mutation ( xref ) xref , xref , the R353G mutant channels were localized to the AIS and axonal surface to a similar extent as the wild-type channels ( xref )."
sparser
"Disruption of CaM binding to KCNQ2 inhibits enrichment of HA-KCNQ3/KCNQ2 channels at the axonal surface."
sparser
"However, in contrast to the wild-type KCNQ2 subunit, addition of 100 µM calcium further increased binding of CaM to KCNQ2(C527R) ( xref )."
sparser
"Since CaM interaction with KCNQ2 is required for functional expression of KCNQ channels in non-neuronal cells xref , xref , xref , we hypothesized that CaM regulates preferential targeting of KCNQ channels to the axonal surface."
sparser
"In the present study, we show that the IQ motif of KCNQ3 regulates the formation of a stable CaM/KCNQ2/3 complex and the traffic of KCNQ2/3 channels at the AIS."
sparser
"To probe for CaM interactions with KCNQ2–5, we performed immunoprecipitation (IP) experiments, followed by immunoblotting."
sparser
"CaM was able to bind KCNQ2(C527R) protein in the calcium (–) condition ( xref )."
sparser
"Disruption of CaM binding to KCNQ2 impairs trafficking of HA-KCNQ3/KCNQ2 channels from the ER to the axon."
sparser
"According to xref , calmodulin binding to KCNQ2 channels stabilized PI(4,5)P 2 channel binding."
reach
"Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum."
reach
"Considering the modest effect of CaM1234 on the axonal surface expression of HA-KCNQ3 and KCNQ2 channels (XREF_FIG), CaM bound to KCNQ2 may act as a Ca 2+ sensor for modulating not only the M-current, but also the channel density at the axonal membrane."
reach
"According to XREF_BIBR, calmodulin binding to KCNQ2 channels stabilized PI (4,5) P 2 channel binding."
CALM binds KCNQ2 and IQ. 6 / 6
| 6
sparser
"By utilizing a dominant-negative mutant CaM that is unable to bind Ca 2+ xref or mutations that block or reduce CaM binding xref , xref , we show that CaM interaction with the IQ motif of KCNQ2 is required for exit of KCNQ channels from the endoplasmic reticulum (ER), and their subsequent enrichment at the axonal plasma membranes in cultured hippocampal neurons."
sparser
"These results reflect the differences in the axonal enrichment of wild-type and A343D mutant channels, further supporting a critical role for CaM interaction with the IQ motif of KCNQ2 in regulating axonal surface expression of intact KCNQ channels."
sparser
"Our results with CD4-Q2C proteins ( xref – xref ) suggest that enrichment of intact KCNQ channels at the axonal surface may be mediated by CaM interaction with the IQ motif of KCNQ2."
sparser
"These correlative findings suggest that enrichment of CD4-Q2C and HA-KCNQ3/KCNQ2 channels at the axonal surface requires CaM interaction with the IQ motif of KCNQ2."
sparser
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3/KCNQ2 channels from the ER to the axonal surface ( xref – xref ), the KCNQ2 subunits with de novo xref – xref and BFNC xref mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
sparser
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
CALM binds KCNQ2-C527R. 1 / 1
| 1
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"However, in contrast to the wild-type KCNQ2 subunit, addition of 100 microM calcium further increased binding of CaM to KCNQ2 (C527R) (XREF_FIG)."
Mutated CALM binds KCNQ2. 1 / 1
| 1
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"The first CaM binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2 +-insensitive CaM mutant bind to KCNQ2."
CALM binds KCNQ1 and KCNQ2. 1 / 1
| 1
sparser
"WT and mutant Kv7.1 C-termini and Kv7.2 C-terminus did interact with CaM as assayed by HIS3 induction in the GAL4 based yeast two-hybrid system ( Fig. 4 B) while the negative controls did not produce any signal."
CALM binds KCNQ2 and KCNQ3. 1 / 1
| 1
sparser
"Recent studies have shown that calmodulin (CaM) binds to the KCNQ2 and KCNQ3 C termini and may function as an auxiliary channel subunit xref , xref , xref ."
CALM binds PKC and KCNQ2. 1 / 1
| 1
sparser
"In conclusion, signaling events that can change the configuration of CaM-KCNQ2 binding, such as elevation of intracellular calcium or PKC phosphorylation, lower KCNQ2 affinity toward PIP2."
CALM binds KCNQ2, KCNQ3, and cooH. 1 / 1
| 1
sparser
"Using similar biochemical approaches, both papers demonstrated CaM binding to the intracellular COOH-terminal domains of KCNQ2 and KCNQ3 channels, and disruption of binding by mutagenesis of residues at regions similar to those named IQ 1 and IQ 2 in the present study."
CALM activates KCNQ2.
| 13
CALM activates KCNQ2. 7 / 7
| 7
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"We demonstrate that phosphorylation of calmodulin by protein kinase CK2 (casein kinase 2) rapidly and reversibly modulated KCNQ2 current."
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"These experiments demonstrate that the tethering of CaM to KCNQ channels is essential for their expression at the AIS.We then tested the possibility that CaM expression could rescue the assembly and traffic of KCNQ2 and KCNQ3-I 342A channels in neurons."
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"Meanwhile, calmodulin knockdown reduced KCNQ2 current and increased neuronal activity, showing that hippocampal neuronal excitability is regulated by expression level of calmodulin protein."
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"Nonetheless, CaM induced a comparable increase of KCNQ2-I340A and KCNQ3-I342A or KCNQ2 and KCNQ3-I 342A currents (138% vs. 118%)."
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"Coexpression of Ca 2+ -insensitive CaM has been reported to moderately increase the ER retention of KCNQ2 by 20% in HEK293T cells XREF_BIBR, XREF_BIBR, suggesting that enrichment of KCNQ channels at the axonal surface may be regulated by Ca 2+ -bound CaM."
reach
"Recently, it has been shown by XREF_BIBR that KCNQ2 BNFS causing mutations express alterations in CaM binding and that in some cases CaM overexpression restored normal function of the KCNQ2 and KCNQ3 induced channels."
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"We show that CaM enhances the heteromeric association of KCNQ2 and KCNQ3-I 342A subunits by binding to their B helices in a calcium dependent manner."
CALM bound to KCNQ2 activates KCNQ2. 5 / 5
| 5
reach
"Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2 and KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon."
reach
"Disruption of CaM binding to KCNQ2 impairs trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon."
reach
"Disruption of CaM binding to KCNQ2 inhibits enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface."
reach
"To test whether CaM binding to KCNQ2 promotes trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon, we performed pulse-chase experiments after removal of BFA."
reach
"These results together indicate that disruption of CaM interaction with KCNQ2 by the A343D mutation impairs the trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon."
CALM activates KCNQ2-S511D. 1 / 1
| 1
reach
"Alaimo and co-workers (Alaimo et al., 2013) have also documented that CaM enhances the functionality of KCNQ2-I340A and KCNQ2 S511D mutants."
CALM inhibits KCNQ2.
| 5
CALM inhibits KCNQ2. 4 / 4
| 4
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"We found that CaM, but not CaM 1234, increased the axonal targeting of KCNQ2 and KCNQ3-I 342A channels compared to mock plasmid."
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"Calmodulin activation limits the rate of KCNQ2 K+ channel exit from the endoplasmic reticulum."
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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."
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"Moreover, overexpression of CaM reduced current amplitudes of KCNQ2, KCNQ4, and KCNQ5, but not those of KCNQ1 and KCNQ3."
CALM bound to calcium(2+) inhibits KCNQ2. 1 / 1
| 1
reach
"In this study, we investigated the molecular mechanism of KCNQ2 current suppression mediated by calcium bound calmodulin."
KCNQ2 affects CALM
| 2 53 38
KCNQ2 binds CALM.
| 1 52 37
| 1 42 35
reach
"These data are entirely consistent with the concept that CaM bound to KCNQ2 acts as a Ca2+ sensor, conferring Ca2+ dependence to the trafficking of the channel to the plasma membrane and fully explaining the requirement of CaM binding for KCNQ2 function."
reach
"Since CaM interaction with KCNQ2 is required for functional expression of KCNQ channels in non neuronal cells XREF_BIBR, XREF_BIBR, XREF_BIBR, we hypothesized that CaM regulates preferential targeting of KCNQ channels to the axonal surface."
sparser
"Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon."
sparser
"These results suggest that a change in the configuration of CaMKCNQ2 binding induced by elevated intracellular calcium led to the reduction in PIP2 affinity of the KCNQ2 channel."
reach
"After the KCNQ2 and CaM complex was purified by immunoprecipitation in calcium (-) condition, dissociation of CaM from KCNQ2 protein was examined by exposing KCNQ2-CaM resin to calcium (XREF_FIG)."
reach
"Since A-kinase-anchoring protein (AKAP) 79 XREF_BIBR, XREF_BIBR regulates CaM binding to KCNQ2 XREF_BIBR and serves as an adaptor protein for CaM and PKC XREF_BIBR, XREF_BIBR, the mechanism responsible for CaM mediated trafficking of KCNQ channels to the axonal surface may well converge with the ability of CaM to modulate PKC dependent inhibition of M-current via AKAP79/150 XREF_BIBR, XREF_BIBR and PIP 2 XREF_BIBR."
sparser
"To test whether CaM interaction with KCNQ2 regulates the targeting of CD4-Q2C to the axonal surface, we introduced point mutations in helix A of KCNQ2 including two BFNC mutations, L339R and R353G xref ( xref )."
sparser
"Here we show that the L339R mutation in helix A, which is linked to human benign neonatal convulsions, perturbs CaM binding to KCNQ2 channels and prevents their correct trafficking to the plasma membrane."
sparser
"These results together indicate that disruption of CaM interaction with KCNQ2 by the A343D mutation impairs the trafficking of HA-KCNQ3/KCNQ2 channels from the ER to the axon."
sparser
"To test whether CaM binding to KCNQ2 promotes trafficking of HA-KCNQ3/KCNQ2 channels from the ER to the axon, we performed pulse-chase experiments after removal of BFA."
sparser
"As suggested by secondary structure prediction, the mutation residue is likely to disrupt the amphipatic a-helical structure in helix B, which appears to be necessary for proper interaction of CaM with Kv7.2 [12–15,20,32] ."
sparser
"The R353G mutation located distal to the IQ motif ( xref ) has been shown to moderately reduce CaM binding to KCNQ2 in HEK293T cells xref , xref ."
sparser
"CaM binds simultaneously to two sites of Kv7.2 in a 1∶1 stoichiometry xref ; xref ."
sparser
"The current study suggests that not only the calcium-induced dissociation of CaM, but also a change in the configuration of CaM-KCNQ2 binding could suppress the KCNQ2 current."
sparser
"Moreover, binding of WT CaM to KCNQ2 can moderately reduce the constitutive current through KCNQ2 homomeric channels by changing channel structure ( xref )."
sparser
"These results support the hypothesis that changes in calcium levels alter KCNQ2-CaM binding, which leads to the suppression of the current."
sparser
"Both WT and dominant-negative CaM bind to the C terminus of KCNQ2 ( xref ) and (a) mutations in KCNQ2 that affect CaM binding, (b) expression of dominant-negative CaM, or (c) expression of a “CaM sponge” lead to retention of KCNQ2 homomeric channels in the ER ( xref ; xref ; xref )."
reach
"The second group found that both wt CaM and DN CaM interact with KCNQ2, consistent with our results that DN CaM can act as a dominant negative in CaM actions."
sparser
"The interaction of the Kv7.2 C-terminus with CaM was used as positive control."
sparser
"Since the KCNQ2(R353G) channel with impaired CaM binding and low PIP2 affinity xref showed a stronger response to ionomycin, it would be reasonable to assume that the KCNQ2-CaM interaction regulates PIP2 affinity of the KCNQ2 subunit as we reported previously xref ."
reach
"In contrast, the A343D mutation, which blocked CaM binding to KCNQ2 (XREF_FIG) XREF_BIBR, XREF_BIBR, abolished surface and intracellular expression of HA-KCNQ3 and KCNQ2 channels at the AIS and distal axons (XREF_FIG, XREF_FIG) and reduced the surface " Axon and Dendrite " ratio to below 1 (XREF_FIG)."
reach
"Recent studies have shown that calmodulin (CaM) binds to the KCNQ2 and KCNQ3 C termini and may function as an auxiliary channel subunit XREF_BIBR, XREF_BIBR, XREF_BIBR."
sparser
"CK2 phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating Ca 2+ gating of SK2 channels."
reach
"In addition, Ca 2 + / CaM binds the 1-5-10 motifs of both KCNQ2 and KCNQ3 with a low-affinity, and favours subunit interaction."
reach
"The structural elements critical for CaM binding to KCNQ2 lie in two conserved motifs in the proximal half of the channel C-terminal domain."
sparser
"CK2phosphorylated SK2-bound CaM but not KCNQ2-bound CaM, thereby selectively regulating SK2 channels."
reach
"Disruption of CaM binding to KCNQ2 impairs trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon."
reach
"To test whether CaM interaction with KCNQ2 regulates the targeting of CD4-Q2C to the axonal surface, we introduced point mutations in helix A of KCNQ2 including two BFNC mutations, L339R and R353G XREF_BIBR (XREF_FIG)."
reach
"CK2phosphorylated SK2 bound CaM but not KCNQ2 bound CaM, thereby selectively regulating SK2 channels."
sparser
"These results together suggest that disruption of CaM binding to KCNQ2 impairs the trafficking of CD4-Q2C proteins from the ER to the AIS and distal axons."
reach
"Despite a modest reduction of CaM binding to KCNQ2 by the R353G mutation (XREF_FIG) XREF_BIBR, XREF_BIBR, the R353G mutant channels were localized to the AIS and axonal surface to a similar extent as the wild-type channels (XREF_FIG)."
reach
"To test whether CaM binding to KCNQ2 promotes trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon, we performed pulse-chase experiments after removal of BFA."
reach
"Since the R353G mutation in KCNQ2 reduces CaM binding to heteromeric KCNQ2 and KCNQ3 channels only by 20% XREF_BIBR, XREF_BIBR, our results suggest that a greater degree of impairment in CaM binding to KCNQ2 is needed to prevent targeting of heteromeric channels to the axonal surface."
sparser
"These data are entirely consistent with the concept that CaM bound to KCNQ2 acts as a Ca2+ sensor, conferring Ca2+ dependence to the trafficking of the channel to the plasma membrane and fully explaining the requirement of CaM binding for KCNQ2 function."
reach
"Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2 and KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon."
sparser
"Calmodulin (CaM) binds to two intracellular C-terminal segments of Kv7.2 channels, helices A and B, and it is required for exit from the endoplasmic reticulum."
sparser
"Our prediction thus supports these results by highlighting the importance of the interactions between KCNQ2 and the CaM proteins."
sparser
"Considering the modest effect of CaM1234 on the axonal surface expression of HA-KCNQ3/KCNQ2 channels ( xref ), CaM bound to KCNQ2 may act as a Ca 2+ sensor for modulating not only the M-current, but also the channel density at the axonal membrane."
sparser
"The process appears to require at least two steps; the first involves the transient association of CaM with KCNQ2, and in the second, the complex adopts an "active" conformation that is more stable and is that which confers the capacity to exit the endoplasmic reticulum."
sparser
"Although CaM can still interact with KCNQ3 subunits xref , xref , the A343D mutation, which abolished CaM binding to KCNQ2 ( xref ), prevented surface and intracellular expression of intact HA-KCNQ3/KCNQ2 channels at the AIS and distal axons ( xref – xref ), consistent with a recent study reporting altered neuronal distribution of heteromeric channels by the I340A mutation xref ."
reach
"Disruption of CaM binding to KCNQ2 inhibits enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface."
sparser
"In contrast, the BFNC R353G mutation located distal to the IQ motif modestly reduced but did not abolish CaM binding to KCNQ2 ( xref ) and had minimal effect on the polarized axonal surface expression of HA-KCNQ3/KCNQ2 channels ( xref )."
reach
"Given the importance that both groups ascribed to both of these regions for CaM binding to KCNQ2 subunits, we were surprised to find in the current work that IQ 2, but not IQ 1, produced a Ca 2+ -dependent gel shift of CaM."
reach
"In this study, we investigated the molecular mechanism of KCNQ2 current suppression mediated by calcium bound calmodulin."
reach
"In contrast, the BFNC R353G mutation located distal to the IQ motif modestly reduced but did not abolish CaM binding to KCNQ2 (XREF_FIG) and had minimal effect on the polarized axonal surface expression of HA-KCNQ3 and KCNQ2 channels (XREF_FIG)."
sparser
"We also demonstrated that a CaM deficient mutant channel, KCNQ2(R353G), showed augmented ionomycin-induced current suppression, which suggests that a change in the KCNQ2-CaM interaction is critical for the suppression."
sparser
"KCNQ2 subunit associates with another CaM binding protein as a constituent of the channel complex: AKAP79/150, a scaffold protein critical for KCNQ2 channel regulation xref , xref ."
reach
"The R353G mutation located distal to the IQ motif (XREF_FIG) has been shown to moderately reduce CaM binding to KCNQ2 in HEK293T cells XREF_BIBR, XREF_BIBR."
sparser
"The first CaM-binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2+-insensitive CaM mutant bind to KCNQ2."
reach
"The first CaM binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2 +-insensitive CaM mutant bind to KCNQ2."
reach
"Calmodulin bound to the KCNQ2 subunit regulates channel trafficking and stabilizes channel activity."
reach
"CK2 phosphorylated SK2 bound CaM but not KCNQ2 bound CaM, thereby selectively regulating Ca 2+ gating of SK2 channels."
reach
"Moreover, binding of WT CaM to KCNQ2 can moderately reduce the constitutive current through KCNQ2 homomeric channels by changing channel structure."
sparser
"Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum."
sparser
"Calmodulin bound to the KCNQ2 subunit regulates channel trafficking and stabilizes channel activity."
sparser
"The second group found that both wt CaM and DN CaM interact with KCNQ2, consistent with our results that DN CaM can act as a dominant negative in CaM actions."
reach
"Here, we have studied this functional interaction using fluorescence and NMR spectroscopy, in order to compare the association between Kv7.2 and full-length CaM 1-148 with that between Kv7.2 and the isolated N- (CaM 1-78) and C-domain (CaM 79-148) fragments XREF_BIBR."
reach
"Although CaM can still interact with KCNQ3 subunits XREF_BIBR, XREF_BIBR, the A343D mutation, which abolished CaM binding to KCNQ2 (XREF_FIG), prevented surface and intracellular expression of intact HA-KCNQ3 and KCNQ2 channels at the AIS and distal axons (XREF_FIG - XREF_FIG), consistent with a recent study reporting altered neuronal distribution of heteromeric channels by the I340A mutation XREF_BIBR."
sparser
"Since the R353G mutation in KCNQ2 reduces CaM binding to heteromeric KCNQ2/KCNQ3 channels only by 20% xref , xref , our results suggest that a greater degree of impairment in CaM binding to KCNQ2 is needed to prevent targeting of heteromeric channels to the axonal surface."
reach
"These results together indicate that disruption of CaM interaction with KCNQ2 by the A343D mutation impairs the trafficking of HA-KCNQ3 and KCNQ2 channels from the ER to the axon."
reach
"Although the binding of CaM with Kv7.2 is not fully recapitulated by its individual segments XREF_BIBR, this analysis helps in understanding how CaM interacts with the channel."
sparser
"Given the importance that both groups ascribed to both of these regions for CaM binding to KCNQ2 subunits, we were surprised to find in the current work that IQ 2 , but not IQ 1 , produced a Ca 2+ -dependent gel shift of CaM."
reach
"Here we show that the L339R mutation in helix A, which is linked to human benign neonatal convulsions, perturbs CaM binding to KCNQ2 channels and prevents their correct trafficking to the plasma membrane."
reach
"These results together suggest that disruption of CaM binding to KCNQ2 impairs the trafficking of CD4-Q2C proteins from the ER to the AIS and distal axons."
reach
"First, we introduced two mutations within the IQ domain of KCNQ3 : an isoleucine to alanine substitution at the position 342 (KCNQ3-I342A); and an alanine substitution of the residues 346 to 349 (KCNQ3-WRYY; Fig. 1 A) which are also involved in the binding of CaM to KCNQ2 and Nav1.2 channels (Feldkamp et al., 2012; Wen and Levitan, 2002)."
sparser
"Despite a modest reduction of CaM binding to KCNQ2 by the R353G mutation ( xref ) xref , xref , the R353G mutant channels were localized to the AIS and axonal surface to a similar extent as the wild-type channels ( xref )."
sparser
"Disruption of CaM binding to KCNQ2 inhibits enrichment of HA-KCNQ3/KCNQ2 channels at the axonal surface."
sparser
"However, in contrast to the wild-type KCNQ2 subunit, addition of 100 µM calcium further increased binding of CaM to KCNQ2(C527R) ( xref )."
sparser
"Since CaM interaction with KCNQ2 is required for functional expression of KCNQ channels in non-neuronal cells xref , xref , xref , we hypothesized that CaM regulates preferential targeting of KCNQ channels to the axonal surface."
sparser
"In the present study, we show that the IQ motif of KCNQ3 regulates the formation of a stable CaM/KCNQ2/3 complex and the traffic of KCNQ2/3 channels at the AIS."
sparser
"To probe for CaM interactions with KCNQ2–5, we performed immunoprecipitation (IP) experiments, followed by immunoblotting."
sparser
"CaM was able to bind KCNQ2(C527R) protein in the calcium (–) condition ( xref )."
sparser
"Disruption of CaM binding to KCNQ2 impairs trafficking of HA-KCNQ3/KCNQ2 channels from the ER to the axon."
sparser
"According to xref , calmodulin binding to KCNQ2 channels stabilized PI(4,5)P 2 channel binding."
reach
"Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum."
reach
"Considering the modest effect of CaM1234 on the axonal surface expression of HA-KCNQ3 and KCNQ2 channels (XREF_FIG), CaM bound to KCNQ2 may act as a Ca 2+ sensor for modulating not only the M-current, but also the channel density at the axonal membrane."
reach
"According to XREF_BIBR, calmodulin binding to KCNQ2 channels stabilized PI (4,5) P 2 channel binding."
CALM binds KCNQ2 and IQ. 6 / 6
| 6
sparser
"By utilizing a dominant-negative mutant CaM that is unable to bind Ca 2+ xref or mutations that block or reduce CaM binding xref , xref , we show that CaM interaction with the IQ motif of KCNQ2 is required for exit of KCNQ channels from the endoplasmic reticulum (ER), and their subsequent enrichment at the axonal plasma membranes in cultured hippocampal neurons."
sparser
"These results reflect the differences in the axonal enrichment of wild-type and A343D mutant channels, further supporting a critical role for CaM interaction with the IQ motif of KCNQ2 in regulating axonal surface expression of intact KCNQ channels."
sparser
"Our results with CD4-Q2C proteins ( xref – xref ) suggest that enrichment of intact KCNQ channels at the axonal surface may be mediated by CaM interaction with the IQ motif of KCNQ2."
sparser
"These correlative findings suggest that enrichment of CD4-Q2C and HA-KCNQ3/KCNQ2 channels at the axonal surface requires CaM interaction with the IQ motif of KCNQ2."
sparser
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3/KCNQ2 channels from the ER to the axonal surface ( xref – xref ), the KCNQ2 subunits with de novo xref – xref and BFNC xref mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
sparser
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
CALM binds KCNQ2-C527R. 1 / 1
| 1
reach
"However, in contrast to the wild-type KCNQ2 subunit, addition of 100 microM calcium further increased binding of CaM to KCNQ2 (C527R) (XREF_FIG)."
Mutated CALM binds KCNQ2. 1 / 1
| 1
reach
"The first CaM binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2 +-insensitive CaM mutant bind to KCNQ2."
CALM binds KCNQ1 and KCNQ2. 1 / 1
| 1
sparser
"WT and mutant Kv7.1 C-termini and Kv7.2 C-terminus did interact with CaM as assayed by HIS3 induction in the GAL4 based yeast two-hybrid system ( Fig. 4 B) while the negative controls did not produce any signal."
CALM binds KCNQ2 and KCNQ3. 1 / 1
| 1
sparser
"Recent studies have shown that calmodulin (CaM) binds to the KCNQ2 and KCNQ3 C termini and may function as an auxiliary channel subunit xref , xref , xref ."
CALM binds PKC and KCNQ2. 1 / 1
| 1
sparser
"In conclusion, signaling events that can change the configuration of CaM-KCNQ2 binding, such as elevation of intracellular calcium or PKC phosphorylation, lower KCNQ2 affinity toward PIP2."
CALM binds KCNQ2, KCNQ3, and cooH. 1 / 1
| 1
sparser
"Using similar biochemical approaches, both papers demonstrated CaM binding to the intracellular COOH-terminal domains of KCNQ2 and KCNQ3 channels, and disruption of binding by mutagenesis of residues at regions similar to those named IQ 1 and IQ 2 in the present study."
KCNQ2 phosphorylates CALM.
| 1
KCNQ2 phosphorylates CALM. 1 / 1
| 1
sparser
"We demonstrate that phosphorylation of calmodulin by protein kinase CK2 (casein kinase 2) rapidly and reversibly modulated KCNQ2 current."
KCNQ2 activates CALM.
| 1 1
KCNQ2 activates CALM. 1 / 1
| 1 1
reach
"PKC phosphorylation of the KCNQ2 channel subunit induces dissociation of calmodulin from the M and channel complex."
PKC affects KCNQ2
| 8 11
PKC phosphorylates KCNQ2.
| 7 8
PKC phosphorylates KCNQ2. 15 / 15
| 7 8
reach
"In response to muscarinic agonists, PKC phosphorylates the KCNQ2 subunit and inhibits potassium current through the M channel, an important step in regulating neuronal excitability."
sparser
"PKC phosphorylation of the KCNQ2 channel subunit induces dissociation of calmodulin from the M-channel complex."
sparser
"In response to muscarinic agonists, PKC phosphorylates the KCNQ2 subunit and inhibits potassium current through the M channel, an important step in regulating neuronal excitability."
reach
"Recently, phosphorylation of KCNQ2 by protein kinase C (PKC) has been shown to dissociate CaM from KCNQ2 channels, leading to a reduced affinity to PIP 2 and suppression of M-current XREF_BIBR."
sparser
"Previous work showed AKAP79 to co-precipitate with KCNQ2 channels (Cooper et al., 2000), and to facilitate PKC phosphorylation of KCNQ2 channels (Hoshi et al., 2003)."
sparser
"Muscarinic agonists such as acetylcholine mobilize an anchored pool of PKC that phosphorylates the KCNQ2 subunit of the M channel on Ser 541 to decrease potassium permeability ( xref )."
reach
"PKC phosphorylation of the KCNQ2 channel subunit induces dissociation of calmodulin from the M and channel complex."
reach
"The in vitro kinase assay showed that KCNQ2 subunits of M channel can be phosphorylated by PKC."
sparser
"AKAP79-bound CKAR should be a good proxy for PKC phosphorylation of AKAP79-bound KCNQ2."
reach
"This maintains PKC where it can optimally respond to activating signals from the m1 receptor and preferentially phosphorylate the KCNQ2 subunit."
sparser
"In neurons muscarinic agonists mobilize an AKAP79-anchored pool of PKC that phosphorylates the KCNQ2 subunit of the M channel."
reach
"Previous work showed AKAP79 to co-precipitate with KCNQ2 channels (Cooper et al., 2000), and to facilitate PKC phosphorylation of KCNQ2 channels (Hoshi et al., 2003)."
sparser
"Recently, phosphorylation of KCNQ2 by protein kinase C (PKC) has been shown to dissociate CaM from KCNQ2 channels, leading to a reduced affinity to PIP 2 and suppression of M-current xref ."
reach
"Recent work indicates that protein kinase C (PKC) phosphorylation of the KCNQ2 subunit reduces the affinity for its PIP 2 binding and activities."
reach
"Recent work indicates that protein kinase C (PKC) phosphorylation of the KCNQ2 subunit reduces the affinity for its PIP 2 binding and activities."
PKC binds KCNQ2.
| 1 1
| 1
reach
"AKAP79 bound CKAR should be a good proxy for PKC phosphorylation of AKAP79 bound KCNQ2."
CALM binds PKC and KCNQ2. 1 / 1
| 1
sparser
"In conclusion, signaling events that can change the configuration of CaM-KCNQ2 binding, such as elevation of intracellular calcium or PKC phosphorylation, lower KCNQ2 affinity toward PIP2."
PKC activates KCNQ2.
| 2
PKC activates KCNQ2. 2 / 2
| 2
reach
"However, fusion with AKAP79 to target the reporter to the ion channel, thereby anchoring PKC close to a substrate, abolished this lag : in this configuration, PKC activation and suppression of KCNQ2 currents occurred simultaneously."
reach
"Application of either 8-Cl-AMPc (500 muM), an activator of PKA, or of the phorbol 12-myristate 13-acetate (PMA), an activator of PKC, did not produce variations of the KCNQ2 channel activity (data not shown)."
STX1A affects KCNQ2
| 18
| 15
sparser
"Syntaxin 1A bound strongly to KCNQ2 and Δ372–493 deletion mutant, but did not bind Δ339–360 deletion mutant at all and therefore xref clearly shows that helix A is crucial for the binding."
sparser
"KCNQ2 associates with syntaxin 1A in cortical and hippocampal synaptosomes."
sparser
"The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation."
sparser
"The interaction of syntaxin 1A with KCNQ2 prolonged the activation time constants of this conductance and reduced the conductance of the current roughly twofold ( xref )."
sparser
"Syntaxin 1A strongly associates with KCNQ2 subunits but not with other KCNQ family members in Xenopus oocytes."
sparser
"First, we carried out a comparative examination of the physical interactions of syntaxin 1A with the channels by performing reciprocal coimmunoprecipitation analysis, using antibodies against KCNQ2, KCNQ3 and syntaxin 1A, in oocytes from a single batch coexpressing the subunits with syntaxin 1A. Syntaxin 1A associated with KCNQ2, to a lesser extent with KCNQ2/3 and only weakly with KCNQ3 ( xref )."
sparser
"Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities."
sparser
"We further aimed to establish the role of helix A in the KCNQ2-syntaxin 1A interaction in oocytes by performing a coimmunoprecipitation analysis with two KCNQ2 deletion mutants, one lacking helix A itself (L339-W360) and the second lacking a dispensable stretch that separates helix A from helix B (L372-W493), which served as a control."
sparser
"Quantification over several similar experiments of the intensity ratios of coprecipitated syntaxin 1A to the different channel subunits, coexpressed in the same cells, showed that the amount of syntaxin 1A associated with KCNQ2 was ∼two-, five- and threefold larger than that with KCNQ2/3, KCNQ3 and KCNQ1, respectively ( xref )."
sparser
"In the present study, we demonstrate that syntaxin 1A also associates with KCNQ2 subunits in the brain, leading to modulation of KCNQ2 homomeric channel gating in oocytes."
sparser
"Follow-up experiments to further evaluate the interaction between syntaxin 1A and KCNQ2 at presynaptic terminals were carried out using two different assays in rat cortical and hippocampal synaptosomes."
sparser
"The strong in-vitro binding of syntaxin 1A ( xref ) and the inability of syntaxin 1A to associate with KCNQ2 lacking helix A in oocytes ( xref ), gave support to the notion that helix A is a crucial region for KCNQ2-syntaxin 1A binding."
sparser
"We concluded that the in-vitro binding of syntaxin 1A to KCNQ2 is targeted to a defined region, strong, dose-dependent and saturable."
sparser
"Since our results suggested a strong interaction between syntaxin 1A and KCNQ2 subunits, we checked whether the two proteins colocalize in dissociated cultures of hippocampal neurons."
sparser
"These channels are known to be modulated by syntaxin-1A (Syn-1A) that binds to the C-terminal domain of the Kv7.2 subunit and strongly inhibits M current."
| 3
sparser
"Following our previous studies, in which we characterized syntaxin 1A's interactions with Kv channels xref – xref , xref , xref , we studied the interaction of syntaxin 1A with KCNQ2, KCNQ2/3 and KCNQ3 channels in the heterologous expression system of Xenopus oocytes, where biochemical and electrophysiological analyses can be performed simultaneously."
sparser
"Next, we assessed the functional consequences of syntaxin 1A binding to the KCNQ2, KCNQ2/3 and KCNQ3 channels by two-electrode voltage clamp analysis of currents evoked by depolarizing potentials in oocytes coexpressing the subunits with syntaxin 1A. However, whereas oocytes expressing KCNQ2 alone or together with KCNQ3 exhibited large outward non-inactivating potassium currents, oocytes expressing KCNQ3 alone did not exhibit any detectable current, in agreement with previous studies xref , xref – xref ."
sparser
"In addition, we compared the binding of brain syntaxin 1A to KCNQ2 and KCNQ3 in a pull-down assay from synaptosomes ( xref )."
ANK3 affects KCNQ2
| 10 8
ANK3 binds KCNQ2.
| 10 7
| 9 7
reach
"We have shown that fusion of the KCNQ2 C-terminal tail was sufficient to enrich CD4 at the axonal surface (XREF_FIG - XREF_FIG) regardless of KCNQ2 binding to ankyrin-G (XREF_SUPPLEMENTARY)."
sparser
"Despite the biological and statistical evidence reported here in support of a role for interactions between ANK3 and KCNQ2 in the etio-pathogenesis of BP, there are several limitations of the study that merit consideration."
sparser
"We have shown that fusion of the KCNQ2 C-terminal tail was sufficient to enrich CD4 at the axonal surface ( xref – xref ) regardless of KCNQ2 binding to ankyrin-G ( xref )."
reach
"In line with this role, ANK3 interacts directly with KCNQ2, which is expressed in the brain and forms homomeric and heteromeric voltage gated potassium channels with another member of the KCNQ family, KCNQ3."
sparser
"While none were significant in the second replication sample, the two discovery KCNQ2 SNPs showed significant interactions with five different ANK3 SNPs, supporting potential allelic heterogeneity."
reach
"We found compelling biological evidence for interactions between ANK3 and KCNQ2 based on a bioinformatics search using STRING, and observed congruent statistical evidence of interactions between these genes in association with BP using GWAS data."
reach
"Despite the biological and statistical evidence reported here in support of a role for interactions between ANK3 and KCNQ2 in the etio-pathogenesis of BP, there are several limitations of the study that merit consideration."
reach
"Furthermore, the E810A and D812A mutations in KCNQ2 C-terminus, which disrupt ankyrin-G binding to KCNQ2 XREF_BIBR, XREF_BIBR, XREF_BIBR, reduced the surface " AIS and Axon " ratio of CD4-Q2C to 1, but had no effect on the surface " Axon and Dendrite " ratio (XREF_SUPPLEMENTARY)."
sparser
"Moreover, a different study found an epistatic interaction between ANK3 and KCNQ2 SNPs in bipolar disorder, i.e. the effect of a mutation in one gene was dependent on the mutation present in the other gene [ xref ]."
sparser
"By identifying the causally related variants, will be able to examine in in vivo and in vitro models the mechanisms by which they disrupt the interactions between ANK3 and KCNQ2 and contribute to the molecular underpinnings of BP."
sparser
"We have found intriguing evidence that interactions of ANK3 with KCNQ2 may contribute to susceptibility for BP."
sparser
"We found compelling biological evidence for interactions between ANK3 and KCNQ2 based on a bioinformatics search using STRING, and observed congruent statistical evidence of interactions between these genes in association with BP using GWAS data."
reach
"By identifying the causally related variants, will be able to examine in in vivo and in vitro models the mechanisms by which they disrupt the interactions between ANK3 and KCNQ2 and contribute to the molecular underpinnings of BP."
sparser
"The interactions between ANK3 and KCNQ2 merit further investigation, and if confirmed, may motivate a new line of research into a novel therapeutic target for BP."
reach
"The interactions between ANK3 and KCNQ2 merit further investigation, and if confirmed, may motivate a new line of research into a novel therapeutic target for BP."
sparser
"If the interactions of ANK3 with KCNQ2 can be confirmed to play a role in the etio-pathogenesis of BP, it would motivate a new avenue of research into a novel therapeutic target for this disease."
ANK3 binds KCNQ2, KCNQ3, and voltage-gated potassium channel. 1 / 1
| 1
sparser
"In line with this role, ANK3 interacts directly with KCNQ2, which is expressed in the brain and forms homomeric and heteromeric voltage-gated potassium channels with another member of the KCNQ family, KCNQ3."
ANK3 activates KCNQ2.
| 1
ANK3 activates KCNQ2. 1 / 1
| 1
reach
"ANK3 helps to direct the localization of the KCNQ2 and KCNQ3 channels to the axonal initial segment (AIS) of neurons and nodes of Ranvier."
KCNQ2 affects ANK3
| 10 7
| 9 7
reach
"We have shown that fusion of the KCNQ2 C-terminal tail was sufficient to enrich CD4 at the axonal surface (XREF_FIG - XREF_FIG) regardless of KCNQ2 binding to ankyrin-G (XREF_SUPPLEMENTARY)."
sparser
"Despite the biological and statistical evidence reported here in support of a role for interactions between ANK3 and KCNQ2 in the etio-pathogenesis of BP, there are several limitations of the study that merit consideration."
sparser
"We have shown that fusion of the KCNQ2 C-terminal tail was sufficient to enrich CD4 at the axonal surface ( xref – xref ) regardless of KCNQ2 binding to ankyrin-G ( xref )."
reach
"In line with this role, ANK3 interacts directly with KCNQ2, which is expressed in the brain and forms homomeric and heteromeric voltage gated potassium channels with another member of the KCNQ family, KCNQ3."
sparser
"While none were significant in the second replication sample, the two discovery KCNQ2 SNPs showed significant interactions with five different ANK3 SNPs, supporting potential allelic heterogeneity."
reach
"We found compelling biological evidence for interactions between ANK3 and KCNQ2 based on a bioinformatics search using STRING, and observed congruent statistical evidence of interactions between these genes in association with BP using GWAS data."
reach
"Despite the biological and statistical evidence reported here in support of a role for interactions between ANK3 and KCNQ2 in the etio-pathogenesis of BP, there are several limitations of the study that merit consideration."
reach
"Furthermore, the E810A and D812A mutations in KCNQ2 C-terminus, which disrupt ankyrin-G binding to KCNQ2 XREF_BIBR, XREF_BIBR, XREF_BIBR, reduced the surface " AIS and Axon " ratio of CD4-Q2C to 1, but had no effect on the surface " Axon and Dendrite " ratio (XREF_SUPPLEMENTARY)."
sparser
"Moreover, a different study found an epistatic interaction between ANK3 and KCNQ2 SNPs in bipolar disorder, i.e. the effect of a mutation in one gene was dependent on the mutation present in the other gene [ xref ]."
sparser
"By identifying the causally related variants, will be able to examine in in vivo and in vitro models the mechanisms by which they disrupt the interactions between ANK3 and KCNQ2 and contribute to the molecular underpinnings of BP."
sparser
"We have found intriguing evidence that interactions of ANK3 with KCNQ2 may contribute to susceptibility for BP."
sparser
"We found compelling biological evidence for interactions between ANK3 and KCNQ2 based on a bioinformatics search using STRING, and observed congruent statistical evidence of interactions between these genes in association with BP using GWAS data."
reach
"By identifying the causally related variants, will be able to examine in in vivo and in vitro models the mechanisms by which they disrupt the interactions between ANK3 and KCNQ2 and contribute to the molecular underpinnings of BP."
sparser
"The interactions between ANK3 and KCNQ2 merit further investigation, and if confirmed, may motivate a new line of research into a novel therapeutic target for BP."
reach
"The interactions between ANK3 and KCNQ2 merit further investigation, and if confirmed, may motivate a new line of research into a novel therapeutic target for BP."
sparser
"If the interactions of ANK3 with KCNQ2 can be confirmed to play a role in the etio-pathogenesis of BP, it would motivate a new avenue of research into a novel therapeutic target for this disease."
ANK3 binds KCNQ2, KCNQ3, and voltage-gated potassium channel. 1 / 1
| 1
sparser
"In line with this role, ANK3 interacts directly with KCNQ2, which is expressed in the brain and forms homomeric and heteromeric voltage-gated potassium channels with another member of the KCNQ family, KCNQ3."
Ezogabine affects KCNQ2
1 | 3 9
Ezogabine activates KCNQ2.
1 | 3 6
1 | 3 5
reach
"A previous study reported that PIP2 rundown prevents retigabine activation of KCNQ2 channels."
reach
"Experimental studies have shown retigabine [XREF_BIBR] as well as retigabine derivative HN38 [XREF_BIBR] to significantly increase potassium currents in mutated KCNQ2 channels, suggesting their potential as a targeted therapy for KCNQ2 related epilepsies."
reach
"These results are consistent with voltage clamp studies that demonstrated a leftward shift in the voltage dependence for KCNQ2 activation induced by retigabine [28]."
sparser
"These results are consistent with voltage clamp studies that demonstrated a leftward shift in the voltage dependence for KCNQ2 activation induced by retigabine [28] ."
sparser
"A previous study reported that PIP2 rundown prevents retigabine activation of KCNQ2 channels ( xref )."
reach
"KCNQ2, KCNQ2/Q3, and KCNQ3/Q4 channels were activated to a similar degree as KCNQ4 channels by 10 microM of BMS-204352 and retigabine, respectively."
signor
No evidence text available
sparser
"Retigabine activates mainly heteromeric Kv7.2 and Kv7.3 channels and as a result causes changes in resting membrane potential towards more negative levels (ie hyperpolarization)."
reach
"We further show with the operant behavioral test that oxaliplatin induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine."
Ezogabine activates mutated KCNQ2. 1 / 1
| 1
reach
"102 These cases include individuals with KCNT1 mutations treated with quinidine, XREF_BIBR, XREF_BIBR children with KCNQ2 mutations treated with ezogabine (retigabine), 109 individuals with GRIN2A mutations treated with memantine, XREF_BIBR, XREF_BIBR and patients with so called mTORopathies treated with everolimus."
Ezogabine inhibits KCNQ2.
| 2
| 2
reach
"Orofacial neuropathic pain induced by oxaliplatin : downregulation of KCNQ2 channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel potentiator retigabine."
reach
"Discovery of a retigabine derivative that inhibits KCNQ2 potassium channels."
Ezogabine increases the amount of KCNQ2.
| 1
Ezogabine increases the amount of KCNQ2. 1 / 1
| 1
reach
"Retigabine activates KCNQ2 and KCNQ3 expressed in Chinese Hamster Ovary (CHO) cells with an EC 50 value of 1.7 (Rundfeldt and Netzer, 2000) and 0.34 muM when KCNQ2 and KCNQ3 were expressed in Xenopus oocytes (Wickenden et al., 2000)."
PRMT1 affects KCNQ2
| 13
PRMT1 methylates KCNQ2.
| 6
PRMT1 methylates KCNQ2. 5 / 5
| 5
reach
"GST-KCNQ2 was methylated by Prmt1, but not by other Prmts (XREF_FIG and XREF_FIG)."
reach
"To test whether Prmt1 methylates KCNQ2 in vivo, HEK293T cells expressing HA-KCNQ2 were transfected with control or Prmt1 shRNA, followed by immunoprecipitation with anti-KCNQ2 antibodies and immunoblotting with antibodies to asymmetric dimethylarginine (ADMA) and KCNQ2."
reach
"These results strongly advocate that Prmt1 interacts with and methylates KCNQ2."
reach
"To determine whether Prmt1 methylates KCNQ2, we performed in vitro methylation assays using various bacterially purified GST-Prmts (Prmt1-6) or myc tagged Prmt5 purified from HEK293T cells and GST-KCNQ2 (amino acids 320-449) that contain all of four arginine residues identified by mass spectrometry."
reach
"Prmt1 interacts with and methylates KCNQ2."
Modified PRMT1 leads to the methylation of KCNQ2. 1 / 1
| 1
reach
"Conversely, Prmt1 overexpression enhanced KCNQ2 methylation (XREF_FIG)."
PRMT1 binds KCNQ2.
| 3
| 3
reach
"To investigate a potential interaction between KCNQ2 and Prmt1, co-immunoprecipitation experiments were conducted with HEK293T cells."
reach
"Prmt1 interacts with and methylates KCNQ2."
reach
"These results strongly advocate that Prmt1 interacts with and methylates KCNQ2."
PRMT1 inhibits KCNQ2.
| 1
PRMT1 inhibits KCNQ2. 1 / 1
| 1
reach
"Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP 2 binding, and Prmt1 depletion lowers PIP 2 affinity of KCNQ2 channels and thereby the channel activities."
PRMT1 increases the amount of KCNQ2.
| 1
PRMT1 increases the amount of KCNQ2. 1 / 1
| 1
reach
"Prmt1 knockdown specifically decreased the ADMA positive KCNQ2 levels, suggesting that KCNQ2 methylation is sensitive to Prmt1 levels (XREF_FIG)."
PRMT1 demethylates KCNQ2.
| 1
Modified PRMT1 leads to the demethylation of KCNQ2. 1 / 1
| 1
reach
"Taken together, these data indicate that reduced Prmt1 levels cause hypo methylation of KCNQ2 in the Prmt1 +/- brain."
PRMT1 activates KCNQ2.
| 1
PRMT1 activates KCNQ2. 1 / 1
| 1
reach
"In contrast, overexpression of Prmt1 with HA-KCNQ2 enhanced the affinity of KCNQ2 for PIP 2 (XREF_FIG)."
KCNQ2 affects Akap5
| 5 5
| 2 5
reach
"In addition, the binding between KCNQ2 and AKAP150 was also augmented in the presence of calcium, which may have contributed to an increase in CaM retention (XREF_FIG)."
sparser
"We show here that rat KCNQ2 can bind directly to the multivalent A-kinase-anchoring protein AKAP150."
reach
"For B 2 Rs, the peak of the distribution was at ~ 140 nm from that of AKAP150 and KCNQ2 complexes (XREF_FIG, XREF_SUPPLEMENTARY)."
reach
"The nearest-neighbor analysis shows the distribution for KCNQ2-AKAP150 displaying only one sharp and high peak at ~ 20 nm, whereas the distributions for KCNQ2-M 1 Rs or AKAP150-M 1 Rs also displayed a secondary, broader peak at ~ 92 nm, suggesting that not all M 1 Rs are localized in AKAP150 and KCNQ2 complexes."
reach
"Lastly, we noted the large fraction of KCNQ2 and AKAP150 complexes in NG neurons triple labeled for KCNQ2, TRPV1 and AKAP150, nearly identical to the fraction of all three proteins together (XREF_FIG), associations that were again absent in AKAP150 KO mice."
sparser
"Peptides that block AKAP150 binding to the KCNQ2 channel complex antagonize the muscarinic inhibition of the currents."
reach
"Cells co-expressing KCNQ2 and AKAP150 displayed clusters, of which about half represented isolated KCNQ2 homomers, and about half represented KCNQ2 and AKAP150 complexes (XREF_SUPPLEMENTARY)."
KCN binds KCNQ2 and Akap5. 1 / 1
| 1
sparser
"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
| 1
sparser
"The fraction of complexes representing KCNQ2 or KCNQ3 homomers associated with AKAP150 was very low, as was the fraction of KCNQ2/3 heteromers unpaired with AKAP150."
KCN binds AKAP9, KCNQ2, and Akap5. 1 / 1
| 1
sparser
"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
Ztz240 affects KCNQ2
| 2 7
Ztz240 binds KCNQ2.
| 2 3
KCNQ2 binds ztz240. 5 / 5
| 2 3
reach
"Therefore, Induced Fit, a flexible docking program that considers the flexibilities of both ligand and side chains of a target protein, was applied to simulate the binding of ztz240 to KCNQ2."
sparser
"The model of the ztz240-KCNQ2 interaction clearly describes a broad pocket in the VSD, extending from the extracellular mouth of the VSD to R210 ( xref )."
sparser
"Therefore, Induced Fit, a flexible docking program that considers the flexibilities of both ligand and side chains of a target protein, was applied to simulate the binding of ztz240 to KCNQ2."
reach
"The model of the tetramer of ztz240 and KCNQ2 complex was embedded into a patch of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer and then subjected to a 200-ns MD simulation."
reach
"By substituting the values of the eight parameters listed in Equation (24) into Equations (18-22), we can compute the probabilities of the allowed configurations for ztz240 binding to KCNQ2 (CF0-CF4) at different concentrations."
Ztz240 activates KCNQ2.
| 4
Ztz240 activates KCNQ2. 4 / 4
| 4
reach
"We found that, without any adjustment of parameters produced by fitting the concentration response data of ztz240 potentiating the WT KCNQ2 channel, the concentration response curve of ztz240 activating the WT-F137A heteromeric channel predicted by our statistical thermodynamic model is in good agreement with the experimental data determined here in parallel."
reach
"Ztz240, another KCNQ activator that is distinct from retigabine and ZnPy, potentiates KCNQ2 and KCNQ4 but does not affect KCNQ1 and KCNQ3."
reach
"In the present study, we have demonstrated that our model provides an excellent fit to the concentration response data of ztz240 activating the KCNQ2 channel; the fitting result is much better than the fit by the widely used Hill equation."
reach
"Before that, we obtained a set of concentration response data for ztz240 potentiating KCNQ2 by determining the outward current (I/I 0 values) at different concentrations of ztz240."
Calcium(2+) affects KCNQ2
| 2 7
Calcium(2+) inhibits KCNQ2.
| 4
| 4
reach
"Coexpression of Ca 2+ -insensitive CaM modestly reduces enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface."
reach
"We also demonstrate that elevation of intracellular calcium reduced KCNQ2 affinity toward PIP2, as evaluated by a voltage sensitive PIP2 depleting phosphatase, Ci-VSP XREF_BIBR."
reach
"In addition, this calcium induced KCNQ2 current suppression was prevented by co-expression of a dominant negative CaM, CaM (4DA), which contains alanine mutations in all four EF hand motifs, as reported by Gamper et al.."
reach
"These results suggest that an increase in intracellular calcium suppresses KCNQ2 current by reducing PIP2 affinity due to the change in CaM-KCNQ2 configuration."
| 2 1
sparser
"These results demonstrated that CaM-mediated benefits depend on the binding of Ca 2 + /CaM to the 1–5–10 motifs of KCNQ2 and KCNQ3 subunits."
sparser
"In addition, Ca 2 + /CaM binds the 1–5–10 motifs of both KCNQ2 and KCNQ3 with a low-affinity, and favours subunit interaction ( Fig. 7 )."
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)."
Calcium(2+) activates KCNQ2.
| 2
| 2
reach
"Nonetheless, we find that Ca 2 + / CaM promotes the heteromeric assembly of KCNQ2 and KCNQ3-I 342A channels through binding to the B helices of KCNQ2 and KCNQ3-I342A subunits."
reach
"Thus, Ca 2 + / CaM can partially restore the assembly and traffic of KCNQ2 and KCNQ3-I 342A channels in neurons, but a high proportion of these proteins is still held in the intracellular compartment."
IQ affects KCNQ2
| 6 3
IQ binds KCNQ2.
| 6 2
CALM binds KCNQ2 and IQ. 6 / 6
| 6
sparser
"By utilizing a dominant-negative mutant CaM that is unable to bind Ca 2+ xref or mutations that block or reduce CaM binding xref , xref , we show that CaM interaction with the IQ motif of KCNQ2 is required for exit of KCNQ channels from the endoplasmic reticulum (ER), and their subsequent enrichment at the axonal plasma membranes in cultured hippocampal neurons."
sparser
"These results reflect the differences in the axonal enrichment of wild-type and A343D mutant channels, further supporting a critical role for CaM interaction with the IQ motif of KCNQ2 in regulating axonal surface expression of intact KCNQ channels."
sparser
"Our results with CD4-Q2C proteins ( xref – xref ) suggest that enrichment of intact KCNQ channels at the axonal surface may be mediated by CaM interaction with the IQ motif of KCNQ2."
sparser
"These correlative findings suggest that enrichment of CD4-Q2C and HA-KCNQ3/KCNQ2 channels at the axonal surface requires CaM interaction with the IQ motif of KCNQ2."
sparser
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3/KCNQ2 channels from the ER to the axonal surface ( xref – xref ), the KCNQ2 subunits with de novo xref – xref and BFNC xref mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
sparser
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
| 2
reach
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3 and KCNQ2 channels from the ER to the axonal surface (XREF_FIG - XREF_FIG), the KCNQ2 subunits with de novo XREF_BIBR - XREF_BIBR and BFNC XREF_BIBR mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
reach
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
IQ activates KCNQ2.
| 1
IQ activates KCNQ2. 1 / 1
| 1
reach
"The wild type and R353G mutant channels were also found at the AIS and distal axons, regions where the A343D mutant channels and the CD4-KDEL proteins were absent (XREF_FIG), indicating that the A343D mutation in the IQ motif of KCNQ2 enhances the localization of HA-KCNQ3 and KCNQ2 channels in the ER."
KCNQ2 affects IQ
| 6 2
CALM binds KCNQ2 and IQ. 6 / 6
| 6
sparser
"By utilizing a dominant-negative mutant CaM that is unable to bind Ca 2+ xref or mutations that block or reduce CaM binding xref , xref , we show that CaM interaction with the IQ motif of KCNQ2 is required for exit of KCNQ channels from the endoplasmic reticulum (ER), and their subsequent enrichment at the axonal plasma membranes in cultured hippocampal neurons."
sparser
"These results reflect the differences in the axonal enrichment of wild-type and A343D mutant channels, further supporting a critical role for CaM interaction with the IQ motif of KCNQ2 in regulating axonal surface expression of intact KCNQ channels."
sparser
"Our results with CD4-Q2C proteins ( xref – xref ) suggest that enrichment of intact KCNQ channels at the axonal surface may be mediated by CaM interaction with the IQ motif of KCNQ2."
sparser
"These correlative findings suggest that enrichment of CD4-Q2C and HA-KCNQ3/KCNQ2 channels at the axonal surface requires CaM interaction with the IQ motif of KCNQ2."
sparser
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3/KCNQ2 channels from the ER to the axonal surface ( xref – xref ), the KCNQ2 subunits with de novo xref – xref and BFNC xref mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
sparser
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
| 2
reach
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3 and KCNQ2 channels from the ER to the axonal surface (XREF_FIG - XREF_FIG), the KCNQ2 subunits with de novo XREF_BIBR - XREF_BIBR and BFNC XREF_BIBR mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
reach
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
PRKCA affects KCNQ2
4 3 |
PRKCA phosphorylates KCNQ2.
2 2 |
PRKCA phosphorylates KCNQ2 on S558. 2 / 2
1 1 |
hprd
No evidence text available
signor
"Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process."
PRKCA phosphorylates KCNQ2 on S551. 2 / 2
1 1 |
signor
"Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process."
hprd
No evidence text available
PRKCA increases the amount of KCNQ2.
1 |
PRKCA increases the amount of KCNQ2. 1 / 1
1 |
signor
"Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process."
PRKCA binds KCNQ2.
1 |
1 |
hprd
No evidence text available
PRKCA activates KCNQ2.
1 |
PRKCA activates KCNQ2. 1 / 1
1 |
signor
"Phosphorylation of KCNQ2 channels was increased by muscarinic stimulation; this was prevented either by coexpression with AKAP(DeltaA) or pretreatment with PKC inhibitors that compete with diacylglycerol. These inhibitors also reduced muscarinic inhibition of M-current. | These results suggest that Ser534 and 541 are key sites for PKC phosphorylation, although we have not ruled out the possibility that other PKC sites are involved in this process."
| 7
KCNQ2 activates potassium(1+).
| 4
| 4
reach
"Expression of KCNQ2 in frog (Xenopus laevis) oocytes led to potassium selective currents that activated slowly with depolarization."
reach
"It is suggested that KCNQ2 and KCNQ3 contribute to the formation of the native M-current, a slowly activating and deactivating potassium conductance."
reach
"Co-expression of KCNQ2 and KCNQ3 leads to a large increase of the potassium current, suggesting that the proteins interact as heterodimers."
reach
"KCNQ2 and KCNQ3 K+ channel subunits underlie the muscarinic regulated K+ current (I (KM)), a widespread regulator of neuronal excitability."
KCNQ2 inhibits potassium(1+).
| 3
reach
"Muscarinic agonists such as acetylcholine mobilize an anchored pool of PKC that phosphorylates the KCNQ2 subunit of the M channel on Ser 541 to decrease potassium permeability."
reach
"In response to muscarinic agonists, PKC phosphorylates the KCNQ2 subunit and inhibits potassium current through the M channel, an important step in regulating neuronal excitability."
Mutated KCNQ2 inhibits potassium(1+). 1 / 1
| 1
reach
"Most BFNC mutations reduced the maximum potassium current by about 20-30%, causing haploinsufficiency of the ion channel."
KCN affects KCNQ2
| 4 3
KCN binds KCNQ2.
| 4 1
KCN binds KCNQ2 and KCNQ3. 2 / 2
| 2
sparser
"M-current formed by KCNQ2 and KCNQ3 potassium channel subunits has a key role in the stabilization of membrane potential and thus in neuronal excitability."
sparser
"6 M-current formed by KCNQ2 and KCNQ3 potassium channel subunits has a key role in stabilisation of membrane potential and thus in neural excitability."
| 1
reach
"Expression of a calmodulin binding KCNQ2 potassium channel fragment modulates neuronal M-current and membrane excitability."
KCN binds KCNQ2 and Akap5. 1 / 1
| 1
sparser
"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
KCN binds AKAP9, KCNQ2, and Akap5. 1 / 1
| 1
sparser
"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
KCN activates KCNQ2.
| 2
KCN activates KCNQ2. 2 / 2
| 2
reach
"A significant proportion of cases have a genetic origin, and the most frequently mutated gene is KCNQ2, encoding Kv7.2, a voltage dependent potassium channel subunit, leading to so called KCNQ2 related epileptic encephalopathy (KCNQ2-REE)."
reach
"In 1998, geneticists discovered that BFNC is caused by mutations in a novel potassium channel subunit, KCNQ2."
Syntaxin affects KCNQ2
| 2 4
Syntaxin binds KCNQ2.
| 2 2
| 2
sparser
"To investigate the possible physiological impact of the interaction of syntaxin with KCNQ2 and KCNQ3 we performed numerical simulations."
sparser
"It is important to note that our modeling was designed to qualitatively investigate the physiological impact of the interaction of syntaxin with KCNQ2 and KCNQ3."
KCNQ2 binds 1A and syntaxin. 2 / 2
| 2
reach
"Here, we demonstrated that syntaxin 1A colocalizes with KCNQ2 subunits at hippocampal presynaptic boutons (XREF_FIG), binds to KCNQ2 in both synaptosomal membranes (XREF_FIG) and oocytes (XREF_FIG), and modulates the function of the homomeric KCNQ2 channels expressed in oocytes (XREF_FIG) by slowing the activation rate ~ 2 fold and decreasing the current amplitudes by about 50%; the latter is not due to reduced total expression or cell surface trafficking and stability of the channels (XREF_FIG)."
reach
"Interestingly, syntaxin 1A also bound a tandem of helices B+C of KCNQ2 (albeit to a much lesser extent than helix A), although it did not interact with helix B alone."
Syntaxin decreases the amount of KCNQ2.
| 1
Syntaxin decreases the amount of KCNQ2. 1 / 1
| 1
reach
"Both methods provided very similar assessment of PM expressions, indicating that syntaxin 1A did not impair KCNQ2 PM levels (XREF_FIG)."
Syntaxin activates KCNQ2.
| 1
Syntaxin bound to KCNQ2 and 1A activates KCNQ2. 1 / 1
| 1
reach
"Here, we demonstrated that syntaxin 1A colocalizes with KCNQ2 subunits at hippocampal presynaptic boutons (XREF_FIG), binds to KCNQ2 in both synaptosomal membranes (XREF_FIG) and oocytes (XREF_FIG), and modulates the function of the homomeric KCNQ2 channels expressed in oocytes (XREF_FIG) by slowing the activation rate ~ 2 fold and decreasing the current amplitudes by about 50%; the latter is not due to reduced total expression or cell surface trafficking and stability of the channels (XREF_FIG)."
KCNQ2 affects ztz240
| 2 4
KCNQ2 binds ztz240.
| 2 3
KCNQ2 binds ztz240. 5 / 5
| 2 3
reach
"Therefore, Induced Fit, a flexible docking program that considers the flexibilities of both ligand and side chains of a target protein, was applied to simulate the binding of ztz240 to KCNQ2."
sparser
"The model of the ztz240-KCNQ2 interaction clearly describes a broad pocket in the VSD, extending from the extracellular mouth of the VSD to R210 ( xref )."
sparser
"Therefore, Induced Fit, a flexible docking program that considers the flexibilities of both ligand and side chains of a target protein, was applied to simulate the binding of ztz240 to KCNQ2."
reach
"The model of the tetramer of ztz240 and KCNQ2 complex was embedded into a patch of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer and then subjected to a 200-ns MD simulation."
reach
"By substituting the values of the eight parameters listed in Equation (24) into Equations (18-22), we can compute the probabilities of the allowed configurations for ztz240 binding to KCNQ2 (CF0-CF4) at different concentrations."
KCNQ2 inhibits ztz240.
| 1
Mutated KCNQ2 inhibits ztz240. 1 / 1
| 1
reach
"Indeed, mutation of KCNQ2 F137 to alanine (F137A) dramatically reduced ztz240 activity (XREF_FIG)."
CALM affects IQ, and KCNQ2
| 6
CALM binds KCNQ2 and IQ. 6 / 6
| 6
sparser
"By utilizing a dominant-negative mutant CaM that is unable to bind Ca 2+ xref or mutations that block or reduce CaM binding xref , xref , we show that CaM interaction with the IQ motif of KCNQ2 is required for exit of KCNQ channels from the endoplasmic reticulum (ER), and their subsequent enrichment at the axonal plasma membranes in cultured hippocampal neurons."
sparser
"These results reflect the differences in the axonal enrichment of wild-type and A343D mutant channels, further supporting a critical role for CaM interaction with the IQ motif of KCNQ2 in regulating axonal surface expression of intact KCNQ channels."
sparser
"Our results with CD4-Q2C proteins ( xref – xref ) suggest that enrichment of intact KCNQ channels at the axonal surface may be mediated by CaM interaction with the IQ motif of KCNQ2."
sparser
"These correlative findings suggest that enrichment of CD4-Q2C and HA-KCNQ3/KCNQ2 channels at the axonal surface requires CaM interaction with the IQ motif of KCNQ2."
sparser
"Since inhibition of CaM binding to the IQ motif of KCNQ2 completely blocks the targeting of heteromeric HA-KCNQ3/KCNQ2 channels from the ER to the axonal surface ( xref – xref ), the KCNQ2 subunits with de novo xref – xref and BFNC xref mutations in the IQ motif would likely exert a dominant negative effect by forming channels with KCNQ3 and retaining them in the ER."
sparser
"These results collectively support the idea that disruption of CaM binding to the IQ motif of KCNQ2 retains intact heteromeric channels in the ER of cultured hippocampal neurons."
Pyraclofos affects KCNQ2
| 1 4
| 1 4
reach
"Expression of individual KCNQ subunits in tsA cells revealed voltage independent augmentation of KCNQ2, but not KCNQ1 nor KCNQ3, currents by NEM indicating that this action on SCG M currents likely localizes to KCNQ2."
reach
"A number of antibodies to subunits from different classes of potassium channels were used, including the large conductance Ca 2+ -activated K + channel (BK or KCNMA1), the voltage activated K + channels KCNQ2, Kv1.5 (KCNA5), Kv2.1 (KCNB1), Kv3.2 (KCNC2), Kv3.4 (KCNC4), Kv4.3 (KCND3), and the auxiliary voltage activated K + channel subunit Kvbeta (KCNA)."
sparser
"Retigabine, an analogue of flupirtine, shifted the voltage activation of mutated KCNQ2 channels to more hyperpolarized potentials, and also increased the current amplitude [ xref ]."
reach
"Retigabine, an analogue of flupirtine, shifted the voltage activation of mutated KCNQ2 channels to more hyperpolarized potentials, and also increased the current amplitude [XREF_BIBR]."
reach
"This substitution led to a shift of voltage dependent activation of KCNQ2 and a dramatic slowing of activation upon depolarization."
KCNQ2 affects KCN
| 4 1
KCN binds KCNQ2 and KCNQ3. 2 / 2
| 2
sparser
"M-current formed by KCNQ2 and KCNQ3 potassium channel subunits has a key role in the stabilization of membrane potential and thus in neuronal excitability."
sparser
"6 M-current formed by KCNQ2 and KCNQ3 potassium channel subunits has a key role in stabilisation of membrane potential and thus in neural excitability."
| 1
reach
"Expression of a calmodulin binding KCNQ2 potassium channel fragment modulates neuronal M-current and membrane excitability."
KCN binds KCNQ2 and Akap5. 1 / 1
| 1
sparser
"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
KCN binds AKAP9, KCNQ2, and Akap5. 1 / 1
| 1
sparser
"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
KCNQ2 affects CD4
| 5
KCNQ2 activates CD4. 5 / 5
| 5
reach
"A previous report XREF_BIBR as well as our results (XREF_FIG, XREF_SUPPLEMENTARY) indicated that the membrane proximal region of the KCNQ2 C-terminal tail, upstream of the ankyrin-G binding domain, was sufficient to preferentially target CD4 to the axonal surface."
reach
"Fusion of KCNQ2 C-terminal tail deficient in CaM binding fails to preferentially target CD4 to the axonal surface."
reach
"These results together indicate that fusion of KCNQ2 C-terminal tail deficient in CaM binding fails to preferentially target CD4 to the axonal surface."
reach
"Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum."
reach
"Fusion of KCNQ2 C-terminal tail preferentially targets CD4 to the axonal surface."
SP1 affects KCNQ2
1 | 2 1
SP1 increases the amount of KCNQ2.
1 | 1
SP1 increases the amount of KCNQ2. 2 / 2
1 | 1
reach
"We show that the transcription factor Sp1 activates expression of both KCNQ2 and KCNQ3, whereas the transcriptional repressor REST (repressor element 1 silencing transcription factor) represses expression of both of these genes."
trrust
No evidence text available
SP1 binds KCNQ2.
| 1
| 1
sparser
"These sequences are evolutionarily conserved and we show that Sp1 directly interacts with the KCNQ2 promoter in vitro and that removal or mutation of these sequences results in reduced activity of the promoters."
SP1 activates KCNQ2.
| 1
SP1 activates KCNQ2. 1 / 1
| 1
sparser
"SP1 has a long-lasting increased activity in kainate-induced epilepsy model, and neonatal epilepsy-associated KCNQ2 and KCNQ3 genes are activated by SP1 (Feng et al., xref ; Mucha et al., xref )."
PKA affects KCNQ2
| 1 3
PKA phosphorylates KCNQ2.
| 1 1
PKA phosphorylates KCNQ2 on S52. 2 / 2
| 1 1
sparser
"Of the residues found phosphorylated in mouse brain ( xref ), PKA phosphorylation of KCNQ2 at S52 has been shown to enhance KCNQ2 currents in heterologous cells ( xref )."
reach
"Of the residues found phosphorylated in mouse brain (XREF_TABLE), PKA phosphorylation of KCNQ2 at S52 has been shown to enhance KCNQ2 currents in heterologous cells."
PKA activates KCNQ2.
| 2
PKA activates KCNQ2. 2 / 2
| 2
reach
"Downstream genes, in turn, form 2 groups : 1) functionally activated ones that include transcription factors (like Nfatc2 that is functionally activated by PKA dependent glycogen synthase kinase-3beta inactivation) or any cellular function effectors (like Kcnq2 that is functionally activated by PKA dependent phosphorylation) and 2) transcriptionally activated, which also include transcription factors (like Per2) and molecules that participate in some cellular process (like Pon1)."
reach
"Application of either 8-Cl-AMPc (500 muM), an activator of PKA, or of the phorbol 12-myristate 13-acetate (PMA), an activator of PKC, did not produce variations of the KCNQ2 channel activity (data not shown)."
KCNQ2 affects CASP3
| 4
KCNQ2 activates CASP3. 4 / 4
| 4
reach
"Supporting a mediating role of KCNQ2/3 channels in apoptosis, expression of KCNQ2 or KCNQ2/3 channels in Chinese hamster ovary (CHO) cells initiated caspase-3 activation."
reach
"Expression of either homogenous KCNQ2 or heterogeneous KCNQ2/3 channels caused significant activation of caspase-3 after 24 hrs when compared with vector transfected control CHO cells."
reach
"More specifically, expression of KCNQ2 or KCNQ2/3 channels in Chinese hamster ovary (CHO) cells initiated caspase-3 activation."
reach
"Supporting a mediating role in apoptosis, expression of KCNQ2 or KCNQ2/3 channels in CHO cells initiated caspase-3 activation."
KCNQ2 affects BDNF
| 4
KCNQ2 increases the amount of BDNF.
| 2
KCNQ2 increases the amount of BDNF. 2 / 2
| 2
reach
"In addition, EBN administration in maternal mice can increase the levels of BDNF and boost the growth and differentiation of neurons among their generations."
reach
"These data indicate that EBN administrated offspring show increased levels of hippocampal BDNF and these offspring also show stronger dendritic differentiation of new hippocampal neurons during early postnatal development."
KCNQ2 activates BDNF.
| 2
KCNQ2 activates BDNF. 2 / 2
| 2
reach
"It implied that the intake of EBN by female mice during pregnancy and lactation periods can promote the synthesis of BDNF and facilitate the differentiation and growth of neurons."
reach
"These results demonstrated that EBN administrated in maternal mice can increase hippocampal BDNF production of the offspring and the BDNF variation trend paralleled the increase in their learning performance."
KCNQ2 affects AKAP5
| 3 1
| 3 1
sparser
"AKAP79-bound CKAR should be a good proxy for PKC phosphorylation of AKAP79-bound KCNQ2."
reach
"AKAP79 bound CKAR should be a good proxy for PKC phosphorylation of AKAP79 bound KCNQ2."
sparser
"TIRF/FRET experiments revealed cotransfection of wild-type, but not dominant-negative (DN), CaM that cannot bind Ca(2+), to disrupt the interaction of YFP-tagged AKAP79(1-153) with CFP-tagged KCNQ2-5."
sparser
"AKAP79 binds to the C terminus of the KCNQ2 subunit ( xref , xref ) and coordinates the localization of cAMP-dependent protein kinase and PKC."
| 3
reach
"However, our results are consistent with the previous findings in HEK293T cells that CaM1234 modestly increases ER retention of wild-type KCNQ2 by 20% XREF_BIBR, XREF_BIBR."
reach
"Coexpression of Ca 2+ -insensitive CaM has been reported to moderately increase the ER retention of KCNQ2 by 20% in HEK293T cells XREF_BIBR, XREF_BIBR, suggesting that enrichment of KCNQ channels at the axonal surface may be regulated by Ca 2+ -bound CaM."
reach
"Temperature elevation caused an unexpected increase in voltage dependent KCNQ2 channel activation but also increased the endoplasmic reticulum (ER) retention of KCNQ2 protein, and the ER retention was greater for mutants associated with BFNC than for wt KCNQ2."
| 2 1
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 ])."
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."
reach
"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."
KCNQ2 affects pyraclofos
| 3
KCNQ2 activates pyraclofos.
| 2
| 2
reach
"The long kcnq2 variant, transfected into mammalian cells, produces a more slowly activating voltage gated K (+) current; co-transfection of the shorter variant with the longer variant results in attenuation of the K (+) current [XREF_BIBR]."
reach
"Individually, expression of KCNQ2 or KCNQ3 in Xenopus oocytes elicits voltage gated, rapidly activating K +-selective currents similar to KCNQ1."
KCNQ2 inhibits pyraclofos.
| 1
| 1
reach
"The long kcnq2 variant, transfected into mammalian cells, produces a more slowly activating voltage gated K (+) current; co-transfection of the shorter variant with the longer variant results in attenuation of the K (+) current [XREF_BIBR]."
| 3
reach
"EBN attenuated high fat diet induced inflammation."
reach
"The data demonstrated that EBN attenuated high fat diet induced oxidative stress and inflammation partly through transcriptional regulation of hepatic antioxidant and inflammation related genes, better than Simvastatin."
reach
"In the present study, EBN also attenuated EBN induced inflammatory response after 12weeks of intervention."
KCNQ2 affects cell growth
| 3
| 3
reach
"There was no significant Caco-2 cell growth after being treated with various concentrations of EBN at different intervals of time."
reach
"Inhibition of KCNQ2 prevented cell growth and (86) Rb uptake in MDA-MB453 cells but not in MCF-10A cells."
reach
"In contrast, no significant cell growth was seen after being treated with various concentrations of EBN."
KCNQ2 affects calcium(2+)
| 2 1
sparser
"These results demonstrated that CaM-mediated benefits depend on the binding of Ca 2 + /CaM to the 1–5–10 motifs of KCNQ2 and KCNQ3 subunits."
sparser
"In addition, Ca 2 + /CaM binds the 1–5–10 motifs of both KCNQ2 and KCNQ3 with a low-affinity, and favours subunit interaction ( Fig. 7 )."
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)."
KCNQ2 affects PRMT1
| 3
| 3
reach
"To investigate a potential interaction between KCNQ2 and Prmt1, co-immunoprecipitation experiments were conducted with HEK293T cells."
reach
"Prmt1 interacts with and methylates KCNQ2."
reach
"These results strongly advocate that Prmt1 interacts with and methylates KCNQ2."
KCNQ2 affects KCNQ3, and STX1A
| 3
| 3
sparser
"Following our previous studies, in which we characterized syntaxin 1A's interactions with Kv channels xref – xref , xref , xref , we studied the interaction of syntaxin 1A with KCNQ2, KCNQ2/3 and KCNQ3 channels in the heterologous expression system of Xenopus oocytes, where biochemical and electrophysiological analyses can be performed simultaneously."
sparser
"Next, we assessed the functional consequences of syntaxin 1A binding to the KCNQ2, KCNQ2/3 and KCNQ3 channels by two-electrode voltage clamp analysis of currents evoked by depolarizing potentials in oocytes coexpressing the subunits with syntaxin 1A. However, whereas oocytes expressing KCNQ2 alone or together with KCNQ3 exhibited large outward non-inactivating potassium currents, oocytes expressing KCNQ3 alone did not exhibit any detectable current, in agreement with previous studies xref , xref – xref ."
sparser
"In addition, we compared the binding of brain syntaxin 1A to KCNQ2 and KCNQ3 in a pull-down assay from synaptosomes ( xref )."
KCNQ2 affects INS
| 3
KCNQ2 inhibits INS. 3 / 3
| 3
reach
"The data thus far indicated that EBN is able to prevent insulin resistance in rats fed HFD over 12 weeks."
reach
"The results suggest that EBN may be used as functional food to prevent insulin resistance."
reach
"EBN however is able to prevent insulin resistance by preventing some of the transcriptional changes on insulin signaling genes induced by HFD."
KCNQ2 affects Collagen
| 3
sparser
"There was also no effect of inhibiting α2 on hNSPC binding to collagen ( xref )."
sparser
"This clarified that collagen-binding integrins containing the β1 subunit (i.e., α1β1, α2β1, or α3β1 xref ) facilitate hNSPC binding to the recombinant collagen substrates."
sparser
"Integrins α1 and β1 Play a Role in hNSPC Binding to Recombinant Collagen Substrates."
CK2 affects KCNQ2
| 1 2
CK2 phosphorylates KCNQ2.
| 1 1
CK2 phosphorylates KCNQ2. 2 / 2
| 1 1
reach
"Phosphorylation of KCNQ2 and KCNQ3 anchor domains by protein kinase CK2 (CK2) augments binding, as previously shown for Nav1.2."
sparser
"Phosphorylation of KCNQ2 and KCNQ3 anchor domains by protein kinase CK2 (CK2) augments binding, as previously shown for Nav1.2."
CK2 activates KCNQ2.
| 1
CK2 activates KCNQ2. 1 / 1
| 1
reach
"Accordingly, application of CK2 selective inhibitors suppressed KCNQ2 current."
APP affects KCNQ2
| 3
APP decreases the amount of KCNQ2.
| 2
APP decreases the amount of KCNQ2. 2 / 2
| 2
reach
"In the hippocampus, the expression of the KCNQ 2 is probably reduced by the Abeta induced damage."
reach
"In this sense, it has been reported that in the septohippocampal system Abeta reduces not only KCNQ2 subunit expression and then, KCNQ conductance, altering the neuronal excitability but also the expression of the oxidative stress related genes superoxide dismutase 1 (SOD1), 8-oxoguanine DNA glycosylase (OGG1), and monamine oxidase A (MAOA)."
APP inhibits KCNQ2.
| 1
APP inhibits KCNQ2. 1 / 1
| 1
reach
"It has also been reported that Kcnq2 gene is down-regulated by Abeta in the hippocampus [XREF_BIBR] and, in this conditions, M-type K current reduction would rapidly increase the excitability of hippocampal principal and GABAergic interneurons, impairing rhythmicity and synchronic activities [XREF_BIBR, XREF_BIBR]."
| 2
| 2
reach
"Our results indicate that BFNC is caused by a decreased potassium current impairing repolarization of the neuronal cell membrane, which results in hyperexcitability of the central nervous system."
reach
"It has been postulated that BFNC is caused by a decreased potassium current impairing repolarization of the neuronal cell membrane, which results in hyperexcitability of the central nervous system."
| 1 1
| 1
reach
"These values are the same rank order and of comparable potencies as those observed when blocking KCl induced activation of KCNQ2."
| 1
sparser
"These values are the same rank order and of comparable potencies as those observed when blocking KCl-induced activation of KCNQ2 ( Fig. 3 )."
| 1 1
sparser
"Our MD simulations indicated that the PIP 2 interaction with the S4-S5 linker of KCNQ2 is not a simple association-dissociation process."
reach
"For KCNQ2 homomers, we have previously shown that their small macroscopic currents are due to their low apparent affinity for PIP 2; thus, an increase in tonic PIP 2 abundance in the membrane increases the KCNQ2 currents by almost 10-fold, to the level typical of KCNQ2/3 heteromers (25)."
Muscarinic affects KCNQ2
| 2
Muscarinic inhibits KCNQ2.
| 1
Muscarinic inhibits KCNQ2. 1 / 1
| 1
reach
"In the present studies, we tested if KCNQ2 and KCNQ3 channel currents (M-current) could be inhibited by activation of muscarinic m5 receptors transiently transfected into human embryonic kidney (HEK) 293T cells.HEK293T cells were kindly provided by Dr. Jamboor K. Vishwanatha (University of Nebraska Medical Center, Omaha)."
Muscarinic decreases the amount of KCNQ2.
| 1
Muscarinic decreases the amount of KCNQ2. 1 / 1
| 1
reach
"Activation of muscarinic m5 receptors inhibits recombinant KCNQ2 and KCNQ3 K+ channels expressed in HEK293T cells."
HoloCaM affects KCNQ2
| 2
HoloCaM inhibits KCNQ2.
| 1
HoloCaM inhibits KCNQ2. 1 / 1
| 1
reach
"However, despite the established role of CaM as a calcium sensor, the molecular mechanism of KCNQ2 current suppression mediated by holoCaM is not well understood."
HoloCaM binds KCNQ2.
| 1
KCNQ2 binds holoCaM. 1 / 1
| 1
reach
"In control experiments in the absence of AKAP150, the binding of holoCaM to KCNQ2 protein was significantly lower than that of apoCaM, as shown in XREF_FIG & XREF_FIG."
Histamine affects KCNQ2
| 2
Histamine inhibits KCNQ2.
| 1
| 1
reach
"Histamine inhibits KCNQ2 and KCNQ3 channel current via recombinant histamine H (1) receptors."
Histamine activates KCNQ2.
| 1
| 1
reach
"However, in previous studies, we found that activation of histamine H 1 receptors significantly decreased both the fast and slow time constants of KCNQ2 and KCNQ3 channel deactivation (Guo and Schofield, 2002b)."
Cho affects KCNQ2
| 2
KCNQ2 binds cho. 2 / 2
| 2
sparser
"CHO-KCNQ2 cells were seeded in wells of 96-well plates at ∼10,000 cells/well and grown until 80–90% confluence at 37°C in a 5% CO2 incubator."
sparser
"CHO-KCNQ2 cells were seeded in wells of 96-well plates at ,10,000 cells/well and grown until 80-90% confluence at 37uC in a 5% CO 2 incubator."
ApoCaM affects KCNQ2
| 2
KCNQ2 binds apoCaM. 2 / 2
| 2
reach
"We interpret this as an indication that apoCaM binds the intact C-termini of KCNQ2 and KCNQ3 channels, and promotes their multimerization."
reach
"Importantly, coexpression of CaM1234 modestly reduced but did not abolish enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface (XREF_FIG), suggesting that KCNQ2 binding to apoCaM but not Ca 2+ -bound CaM is required for targeting the channels to the axonal surface."
TEA affects KCNQ2
| 2
TEA inhibits KCNQ2. 2 / 2
| 2
reach
"A further complication is that the TEA block of KCNQ2 and KCNQ2 +3 has a Hill slope close to unity."
reach
"First, in contrast to the well-known relative insensivity of M-current to TEA (Adams et al., 1982b), KCNQ2 was blocked by TEA with a K d of 160 +/-20 nM."
RTG affects KCNQ2
| 2
RTG inhibits KCNQ2. 2 / 2
| 2
reach
"RTG significantly attenuated KA induced seizure activities in both Kcnq2 Y284C/+ and Kcnq2 A306T/+ mice, and more markedly than PB."
reach
"RTG significantly attenuates KA-induces seizures in Kcnq2 Y284C/+ and Kcnq2 A306T/+ mice."
RNAi affects KCNQ2
| 2
RNAi inhibits KCNQ2. 2 / 2
| 2
reach
"Time course of RNAi mediated knockdown of KCNQ2 in DRG neurons."
reach
"Statistical evaluation of the effect of RNAi mediated KCNQ2 knockdown on RMP and on ICA-27243-mediated hyperpolarization was performed using Student 's t test (GraphPad Prism 5, GraphPad Software, Inc., La Jolla, CA)."
NOG affects KCNQ2
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Transcriptionally active NOG decreases the amount of KCNQ2. 2 / 2
2 |
biopax:ctd
No evidence text available
biopax:ctd
No evidence text available
L-735,821 affects KCNQ2
| 2
L-735,821 inhibits KCNQ2. 2 / 2
| 2
reach
"L-735,821, a benzodiazepine molecule which inhibits the KCNQ1 channel activity (EC50 = 0.08 microM), also blocks KCNQ2 currents (EC50 = 1.5 microM)."
reach
"This, in fact, has already been shown by Tinel et al. (1998) for L-735,821, a novel benzodiazepine that inhibits both KCNQ1 (EC 50 = 0.08 muM) and KCNQ2 (EC 50 = 1.5 muM)."
| 2
| 2
reach
"Deletion of the ankyrin G binding motif of KCNQ2 and KCNQ3 disrupts the channel AIS localization."
reach
"The wild type and R353G mutant channels were also found at the AIS and distal axons, regions where the A343D mutant channels and the CD4-KDEL proteins were absent (XREF_FIG), indicating that the A343D mutation in the IQ motif of KCNQ2 enhances the localization of HA-KCNQ3 and KCNQ2 channels in the ER."
KCNQ2 affects cho
| 2
KCNQ2 binds cho. 2 / 2
| 2
sparser
"CHO-KCNQ2 cells were seeded in wells of 96-well plates at ∼10,000 cells/well and grown until 80–90% confluence at 37°C in a 5% CO2 incubator."
sparser
"CHO-KCNQ2 cells were seeded in wells of 96-well plates at ,10,000 cells/well and grown until 80-90% confluence at 37uC in a 5% CO 2 incubator."
| 2
reach
"These results suggested that low concentration of EBN could synergistically induce cell proliferation, especially in serum containing medium."
reach
"Moreover, acid hydrolysates of EBN have been shown to promote proliferation of human colonic adenocarcinoma (Caco-2) cells [XREF_BIBR]."
KCNQ2 affects apoCaM
| 2
KCNQ2 binds apoCaM. 2 / 2
| 2
reach
"We interpret this as an indication that apoCaM binds the intact C-termini of KCNQ2 and KCNQ3 channels, and promotes their multimerization."
reach
"Importantly, coexpression of CaM1234 modestly reduced but did not abolish enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface (XREF_FIG), suggesting that KCNQ2 binding to apoCaM but not Ca 2+ -bound CaM is required for targeting the channels to the axonal surface."
KCNQ2 affects PKC
| 1 1
| 1
reach
"AKAP79 bound CKAR should be a good proxy for PKC phosphorylation of AKAP79 bound KCNQ2."
CALM binds PKC and KCNQ2. 1 / 1
| 1
sparser
"In conclusion, signaling events that can change the configuration of CaM-KCNQ2 binding, such as elevation of intracellular calcium or PKC phosphorylation, lower KCNQ2 affinity toward PIP2."
KCNQ2 affects KCNQ3, and voltage-gated potassium channel
| 2
KCNQ2 binds KCNQ3 and voltage-gated potassium channel. 2 / 2
| 2
sparser
"Mutations in the voltage-gated potassium channel subunit genes KCNQ2 and KCNQ3 are associated with benign familial neonatal seizures (Leppert and Singh, xref )."
sparser
"In human bodies, ankyrins have been confirmed to bind to the voltage-gated potassium channel subunits KCNQ2 and KCNQ3, regulating their normal functions [ xref ]."
KCNQ2 affects KCNQ3, and syntaxin
| 2
| 2
sparser
"To investigate the possible physiological impact of the interaction of syntaxin with KCNQ2 and KCNQ3 we performed numerical simulations."
sparser
"It is important to note that our modeling was designed to qualitatively investigate the physiological impact of the interaction of syntaxin with KCNQ2 and KCNQ3."
KCNQ2 affects KCNQ3, and calcium(2+)
| 2
sparser
"These results demonstrated that CaM-mediated benefits depend on the binding of Ca 2 + /CaM to the 1–5–10 motifs of KCNQ2 and KCNQ3 subunits."
sparser
"In addition, Ca 2 + /CaM binds the 1–5–10 motifs of both KCNQ2 and KCNQ3 with a low-affinity, and favours subunit interaction ( Fig. 7 )."
KCNQ2 affects GOLM1
2 |
2 |
biogrid
No evidence text available
biogrid
No evidence text available
KCNQ2 affects GNG4
| 2
| 2
sparser
"Common genetic variation in GNG4 and KCNQ2 was associated with cognitive decline."
sparser
"Genetic variation analyses and gene expression data suggest that GNG4 and KCNQ2 may be associated with cognitive decline in normal aging."
KCNQ2 affects CALM3
1 1 |
1 1 |
biogrid
No evidence text available
hprd
No evidence text available
KCNQ2 affects CALM2
1 1 |
1 1 |
hprd
No evidence text available
biogrid
No evidence text available
KCNQ2 affects ARIH2
1 1 |
1 1 |
biogrid
No evidence text available
hprd
No evidence text available
KCNE5 affects KCNQ2
| 2
KCNE5 activates KCNQ2. 2 / 2
| 2
reach
"Neither KCNE4 nor KCNE5 has been found to modulate KCNQ2 (Kv7.2) or KCNQ2/3 (Kv7.2/3) heteromers XREF_BIBR, XREF_BIBR, a primary molecular correlate of the neuronal M-current 56."
reach
"Neither KCNE4 nor KCNE5 has been found to modulate KCNQ2 (Kv7.2) or KCNQ2/3 (Kv7.2/3) heteromers (Grunnet et al., 2002; Angelo et al., 2002), a primary molecular correlate of the neuronal M-current (Wang et al., 1998b)."
KCN affects KCNQ2, and KCNQ3
| 2
KCN binds KCNQ2 and KCNQ3. 2 / 2
| 2
sparser
"M-current formed by KCNQ2 and KCNQ3 potassium channel subunits has a key role in the stabilization of membrane potential and thus in neuronal excitability."
sparser
"6 M-current formed by KCNQ2 and KCNQ3 potassium channel subunits has a key role in stabilisation of membrane potential and thus in neural excitability."
GOLM1 affects KCNQ2
2 |
2 |
biogrid
No evidence text available
biogrid
No evidence text available
GNG4 affects KCNQ2
| 2
| 2
sparser
"Common genetic variation in GNG4 and KCNQ2 was associated with cognitive decline."
sparser
"Genetic variation analyses and gene expression data suggest that GNG4 and KCNQ2 may be associated with cognitive decline in normal aging."
FN1 affects KCNQ2
| 1 1
FN1 binds KCNQ2.
| 1
FN1 binds KCNQ2 and laminin. 1 / 1
| 1
sparser
"In contrast, there was only a slight effect of blocking β1 integrin on hNSPC binding to laminin or fibronectin."
FN1 activates KCNQ2.
| 1
FN1 activates KCNQ2. 1 / 1
| 1
reach
"The EBN, when stimulated by the contralateral FN (and perhaps the SC), enables a special membrane property that causes a high-frequency burst that decays slowly until being inhibited by the contralateral IBN."
ERMAP affects KCNQ2
| 2
ERMAP activates KCNQ2. 2 / 2
| 2
reach
"The EBN, when stimulated by the contralateral FN (and perhaps the SC), enables a special membrane property that causes a high-frequency burst that decays slowly until being inhibited by the contralateral IBN."
reach
"The ipsilateral LLBN and EBN are stimulated by the contralateral SC burst cells."
CaM1234 affects KCNQ2
| 2
CaM1234 inhibits KCNQ2.
| 1
CaM1234 inhibits KCNQ2. 1 / 1
| 1
reach
"Importantly, coexpression of CaM1234 modestly reduced but did not abolish enrichment of HA-KCNQ3 and KCNQ2 channels at the axonal surface (XREF_FIG), suggesting that KCNQ2 binding to apoCaM but not Ca 2+ -bound CaM is required for targeting the channels to the axonal surface."
CaM1234 activates KCNQ2.
| 1
CaM1234 activates KCNQ2. 1 / 1
| 1
reach
"However, our results are consistent with the previous findings in HEK293T cells that CaM1234 modestly increases ER retention of wild-type KCNQ2 by 20% XREF_BIBR, XREF_BIBR."
CALM3 affects KCNQ2
1 1 |
1 1 |
biogrid
No evidence text available
hprd
No evidence text available
CALM2 affects KCNQ2
1 1 |
1 1 |
hprd
No evidence text available
biogrid
No evidence text available
ARIH2 affects KCNQ2
1 1 |
1 1 |
biogrid
No evidence text available
hprd
No evidence text available
| 2
reach
"Assuming that the XE991 sensitive portion entirely represents KCNQ2 currents, 100 muM MTA or 20 muM furamidine inhibited KCNQ2 currents by 79.9 +/- 13.6% and 72.1 +/- 2.1%, respectively."
reach
"Interestingly, MTA and furamidine reduced activities of the triple Cys mutant of KCNQ2 by a similar extent as it did those of the WT KCNQ2 channel, while the mutant was insensitive to H 2 O 2 as expected (XREF_FIG, Figure 9 -- figure supplement 1 -- source data 1)."
1A affects KCNQ2, and syntaxin
| 2
KCNQ2 binds 1A and syntaxin. 2 / 2
| 2
reach
"Here, we demonstrated that syntaxin 1A colocalizes with KCNQ2 subunits at hippocampal presynaptic boutons (XREF_FIG), binds to KCNQ2 in both synaptosomal membranes (XREF_FIG) and oocytes (XREF_FIG), and modulates the function of the homomeric KCNQ2 channels expressed in oocytes (XREF_FIG) by slowing the activation rate ~ 2 fold and decreasing the current amplitudes by about 50%; the latter is not due to reduced total expression or cell surface trafficking and stability of the channels (XREF_FIG)."
reach
"Interestingly, syntaxin 1A also bound a tandem of helices B+C of KCNQ2 (albeit to a much lesser extent than helix A), although it did not interact with helix B alone."
Tamoxifen affects KCNQ2
| 1
| 1
sparser
"Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels."
Receptors affects KCNQ2
| 1
Receptors inhibits KCNQ2. 1 / 1
| 1
reach
"In our studies, KCNQ2 and KCNQ3 channels were inhibited by activation of muscarinic m1, m3, and m5 receptors, but not m2 or m4 receptors."
Pyrithione affects KCNQ2
| 1
Pyrithione activates mutated KCNQ2. 1 / 1
| 1
reach
"Encouragingly, zinc pyrithione activates all homotetrameric KCNQ channels (except KCNQ3) and rescues the function of mutant KCNQ2 channels linked to benign familial neonatal convulsions."
| 1
reach
"Heteromeric KCNQ2 and KCNQ3 currents were modulated by the muscarinic agonist oxotremorine-M (oxo-M) in a manner having all of the characteristics of modulation of native M current in sympathetic neurons."
Oxo-M affects KCNQ2
| 1
Oxo-M activates KCNQ2. 1 / 1
| 1
reach
"Homomeric KCNQ2 and KCNQ3 channels also expressed well and were modulated individually by oxo-M, suggesting that the motifs for modulation are present on both channel subtypes."
Muscarinic receptors affects KCNQ2
| 1
Muscarinic receptors activates KCNQ2. 1 / 1
| 1
reach
"Therefore, we investigated if activation of other muscarinic receptors could also modulate KCNQ2 and KCNQ3 channels."
M3 affects KCNQ2
| 1
M3 inhibits KCNQ2. 1 / 1
| 1
reach
"In our studies, KCNQ2 and KCNQ3 channels were inhibited by activation of muscarinic m1, m3, and m5 receptors, but not m2 or m4 receptors."
Hsa-miR-375 affects KCNQ2
1 |
Transcriptionally active hsa-miR-375 decreases the amount of KCNQ2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
1 |
Transcriptionally active hsa-miR-26b-5p decreases the amount of KCNQ2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
1 |
Transcriptionally active hsa-miR-148b-3p decreases the amount of KCNQ2. 1 / 1
1 |
biopax:mirtarbase
No evidence text available
Disulfur affects KCNQ2
| 1
| 1
reach
"Furthermore, S2 caused significant drop in ROS production suggesting the protective role of EBN as a free radical species scavenger."
| 1
reach
"We show here that perturbation of calmodulin binding leads to endoplasmic reticulum (ER) retention of KCNQ2, reducing the number of channels that reach the plasma membrane."
Benzodiazepine L-364,373 affects KCNQ2
| 1
Benzodiazepine L-364,373 activates KCNQ2. 1 / 1
| 1
reach
"The benzodiazepine L-364,373, which activates KCNQ1 even when expressed alone either in Xenopus oocytes [18] or in COS cells (not shown), is unable to activate the KCNQ2 channel."
Azanide affects KCNQ2
| 1
Azanide activates KCNQ2. 1 / 1
| 1
reach
"Unlike other reported amide activators of KCNQ2, ML213 is the first non biaryl amide reported in the literature."
ApoCaM proteins affects KCNQ2
| 1
KCNQ2 binds apoCaM proteins. 1 / 1
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reach
"Considering a very low level of intracellular Ca 2+ in dissociated hippocampal cultured neurons at rest XREF_BIBR, we propose that apoCaM proteins bind simultaneously to helices A and B of KCNQ2 and KCNQ3 at the ER, with the IQ motif in helix A of KCNQ2 being the dominant domain for apoCaM interaction (XREF_FIG)."
| 1
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"For KCNQ2, the relative expression levels in neurons treated with high-K + or ACh were 2.05 +/- 0.44 (n = 4, p < 0.05), and 1.80 +/- 0.19 (n = 4, p < 0.05), respectively."
ZG2083 affects KCNQ2
| 1
ZG2083 activates KCNQ2. 1 / 1
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"In the conventional patch-clamp recordings, two validated activators ZG1732 and ZG2083 enhanced KCNQ2 currents with EC50 values of 1.04 +/-0.18 mumol/L and 1.37 +/-0.06 mumol/L, respectively."
VCL affects KCNQ2
| 1
VCL inhibits KCNQ2. 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."
TRIM25 affects KCNQ2
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1 |
biogrid
No evidence text available
TG affects KCNQ2
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KCNQ2 binds TG. 1 / 1
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sparser
"A main finding of the present study is that oxaliplatin-induced trigeminal neuropathic pain is associated with significant downregulation of KCNQ2 channel expression in V2 TG neurons."
Syntaxin affects KCNQ2
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reach
"Syntaxin 1A modulates primarily the KCNQ2 currents."
SPP1 affects KCNQ2
| 1
SPP1 inhibits KCNQ2. 1 / 1
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sparser
"We were especially interested in studying patients with LOTS, since they show intrasaccadic decelerations and saccadic hypometria, which might reflect either premature inhibition of ipsilateral EBN by OPN or early discharge of contralateral IBN due to cFN dysfunction."
SLC5A3 affects KCNQ2
| 1
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sparser
"Importantly, the ability of SMIT1 to be upregulated by an extracellular hypertonic solution via the transcription factor tonicity-responsive enhancer binding protein (TonEBP) effectively coupled KCNQ2 electrical activity, and thus membrane excitability, to osmotic potential – suggested to be the physiological role for the functional interaction between KCNQ2 and SMIT1, via a downstream product of SMITI-transported myo -inositol, PIP 2 [ xref ]."
RPS6 affects KCNQ2
| 1
RPS6 activates KCNQ2. 1 / 1
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"Missense variants in the intracellular domain between S2 and S3 are likely to cause B (F) NE, whereas those in S6 and its adjacent regions are more likely to cause KCNQ2 DEE."
REST affects KCNQ2
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REST decreases the amount of KCNQ2. 1 / 1
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trrust
No evidence text available
PRMT8 affects KCNQ2
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PRMT8 leads to the methylation of KCNQ2. 1 / 1
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reach
"We analyzed whether Prmt8 contributes to hypo methylation of KCNQ2 proteins in Prmt1 +/- brains."
PRKACA affects KCNQ2
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PRKACA phosphorylates KCNQ2 on S438. 1 / 1
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biopax:phosphositeplus
No evidence text available
PPP2 affects KCNQ2
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PPP2 activates KCNQ2. 1 / 1
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reach
"Phosphorylation of the KCNQ2 channel typically results in inhibition of the channel activity and expression of PP2A increases KCNQ2 mediated current, suggesting that GSK-3 might be part of a regulatory mechanism that suppress M-currents."
PIP2 rundown affects KCNQ2
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PIP2 rundown inhibits KCNQ2. 1 / 1
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reach
"A previous study reported that PIP2 rundown prevents retigabine activation of KCNQ2 channels."
Oxo-M affects KCNQ2
| 1
Oxo-M inhibits KCNQ2. 1 / 1
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"Pretreatment with BIS IV blocked Oxo-M mediated suppression of KCNQ2 currents (n = 10; XREF_FIG bar 2) whereas pretreatment with BIS 1 had little effect (n = 13; XREF_FIG bar 3)."
OGG1 affects KCNQ2
| 1
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sparser
"XRCC1 107 and 194, hOGG1, KCNQ2, and AT1R are not associated with endometriosis susceptibility."
Li+ affects KCNQ2
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Li+ leads to the dephosphorylation of KCNQ2. 1 / 1
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reach
"GSK3beta phosphorylates the KCNQ2 channel and this phosphorylation is decreased by Li+."
Kv7.2 affects KCNQ2
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Kv7.2 activates KCNQ2. 1 / 1
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"A significant proportion of cases have a genetic origin, and the most frequently mutated gene is KCNQ2, encoding Kv7.2, a voltage dependent potassium channel subunit, leading to so called KCNQ2 related epileptic encephalopathy (KCNQ2-REE)."
Kcnq4/5 affects KCNQ2
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Kcnq4/5 activates KCNQ2. 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."
Kcnq2/3 affects KCNQ2
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Kcnq2/3 activates KCNQ2. 1 / 1
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reach
"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."
KCNQ3-Delta476-498 mutations affects KCNQ2
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KCNQ3-Delta476-498 mutations decreases the amount of KCNQ2. 1 / 1
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reach
"By contrast, KCNQ2-I340A and KCNQ3-Delta476-498 mutations significantly diminished the surface expression of KCNQ2 subunits."
KCNQ3-Delta476-498 mutants affects KCNQ2
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KCNQ2 binds KCNQ3-Delta476-498 mutants. 1 / 1
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reach
"Also, the KCNQ2-I340A and KCNQ3-Delta476-498 mutants strongly interacted with wild-type KCNQ3 and KCNQ2, respectively (Figs. 1 C-D)."
KCNQ2-I340A affects KCNQ2
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KCNQ2-I340A decreases the amount of KCNQ2. 1 / 1
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reach
"By contrast, KCNQ2-I340A and KCNQ3-Delta476-498 mutations significantly diminished the surface expression of KCNQ2 subunits."
KCNQ2 affects sodium atom
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KCNQ2 bound to FGF14 activates sodium atom. 1 / 1
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reach
"FGF14 interacts with KCNQ2 at a site distinct from the FGF14-VGSC interaction surface, thus enabling the bridging of Na V 1.6 and KCNQ2."
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sparser
"Our MD simulations indicated that the PIP 2 interaction with the S4-S5 linker of KCNQ2 is not a simple association-dissociation process."
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"Our study has demonstrated that EBN can dose-dependently protect against LPS induced neuroinflammation and reverse LPS induced memory impairment."
KCNQ2 affects imidazolide
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"KCNQ2 can coassemble with the KCNQ3 subunit to mediate the IM current that regulates neuronal excitability."
KCNQ2 affects holoCaM
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KCNQ2 binds holoCaM. 1 / 1
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"In control experiments in the absence of AKAP150, the binding of holoCaM to KCNQ2 protein was significantly lower than that of apoCaM, as shown in XREF_FIG & XREF_FIG."
KCNQ2 affects hexadecane
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reach
"These data indicate that the decreased expression of KCNQ2 might cause a hyperexcitability of the CNS, which accounts for the mechanism of BFNC."
KCNQ2 affects ezogabine
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"We further show with the operant behavioral test that oxaliplatin induced orofacial mechanical allodynia can be alleviated by the KCNQ2 potentiator retigabine."
KCNQ2 affects dopamine
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"Kcnq2 and Kcnq3 have been shown to mediate the release of dopamine after exposure to ethanol."
| 1
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"Genetic reduction of Kcnq2 also reduces PPI, as does systemic inhibition of M-channels with linopirdine."
KCNQ2 affects coagulation-related genes
| 1
KCNQ2 inhibits coagulation-related genes. 1 / 1
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"The results indicated that EBN could attenuate HFD induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation related genes."
KCNQ2 affects apoCaM proteins
| 1
KCNQ2 binds apoCaM proteins. 1 / 1
| 1
reach
"Considering a very low level of intracellular Ca 2+ in dissociated hippocampal cultured neurons at rest XREF_BIBR, we propose that apoCaM proteins bind simultaneously to helices A and B of KCNQ2 and KCNQ3 at the ER, with the IQ motif in helix A of KCNQ2 being the dominant domain for apoCaM interaction (XREF_FIG)."
KCNQ2 affects ZNF365
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KCNQ2 activates ZNF365. 1 / 1
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reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects TRIM25
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1 |
biogrid
No evidence text available
KCNQ2 affects TG
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KCNQ2 binds TG. 1 / 1
| 1
sparser
"A main finding of the present study is that oxaliplatin-induced trigeminal neuropathic pain is associated with significant downregulation of KCNQ2 channel expression in V2 TG neurons."
KCNQ2 affects SP1
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sparser
"These sequences are evolutionarily conserved and we show that Sp1 directly interacts with the KCNQ2 promoter in vitro and that removal or mutation of these sequences results in reduced activity of the promoters."
KCNQ2 affects SLC5A3
| 1
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sparser
"Importantly, the ability of SMIT1 to be upregulated by an extracellular hypertonic solution via the transcription factor tonicity-responsive enhancer binding protein (TonEBP) effectively coupled KCNQ2 electrical activity, and thus membrane excitability, to osmotic potential – suggested to be the physiological role for the functional interaction between KCNQ2 and SMIT1, via a downstream product of SMITI-transported myo -inositol, PIP 2 [ xref ]."
KCNQ2 affects SIRT1
| 1
KCNQ2 increases the amount of SIRT1. 1 / 1
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reach
"The results indicated that EBN and estrogen enhanced spatial learning and memory and increased serum estrogen and hippocampal SIRT1 expression."
KCNQ2 affects RPL19A
| 1
KCNQ2 inhibits RPL19A. 1 / 1
| 1
reach
"KCNQ2 I205V has a right shifted conductance-to-voltage relationship, suggesting loss of KCNQ2 channel activity at subthreshold membrane potentials is sufficient to drive large changes in L2/3 pyramidal neuronal excitability even in the presence of an intact mAHP."
KCNQ2 affects RB1
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KCNQ2 activates RB1. 1 / 1
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"Inhibition of KCNQ2 prevented cell growth and (86) Rb uptake in MDA-MB453 cells but not in MCF-10A cells."
KCNQ2 affects RAB3GAP1
| 1
| 1
reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects Pk
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KCNQ2 increases the amount of Pk. 1 / 1
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reach
"EBN intervention was able to upregulate expressions of Gck, Pk, and KCNJ11 in both liver and adipose tissues."
KCNQ2 affects PRKCZ
| 1
KCNQ2 activates PRKCZ. 1 / 1
| 1
reach
"Moreover, EBN upregulated mTOR and Prkcz in the liver and adipose tissue but only caused downregulation of MAPK and Ikbkb in the liver indicating that the transcriptional changes induced by EBN had differential effects on insulin signaling genes in liver and adipose."
KCNQ2 affects PRKCA
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1 |
hprd
No evidence text available
KCNQ2 affects OGG1
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sparser
"XRCC1 107 and 194, hOGG1, KCNQ2, and AT1R are not associated with endometriosis susceptibility."
KCNQ2 affects NOS1AP
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KCNQ2 activates NOS1AP. 1 / 1
| 1
reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects NHLRC1, and SCN1B
| 1
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sparser
"For example, SCN1A associates with 10 disease subtypes, while the four genes: KCNQ2, NHLRC1, PCDH19 and SCN1B associate with 9 subtypes."
| 1
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reach
"We proved the idea that maternal administration of EBN during the pregnancy and lactation periods can enhance the levels of sialic acid in maternal mouse milk, which was associated with the improvement of spatial learning performances, the increasing of ChAT or SOD activities, and the decreasing of AChE or MDA activities in palliums and hippocampi of their offspring."
KCNQ2 affects MTOR
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KCNQ2 activates MTOR. 1 / 1
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reach
"Moreover, EBN upregulated mTOR and Prkcz in the liver and adipose tissue but only caused downregulation of MAPK and Ikbkb in the liver indicating that the transcriptional changes induced by EBN had differential effects on insulin signaling genes in liver and adipose."
KCNQ2 affects MAPK
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KCNQ2 activates MAPK. 1 / 1
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reach
"Moreover, EBN upregulated mTOR and Prkcz in the liver and adipose tissue but only caused downregulation of MAPK and Ikbkb in the liver indicating that the transcriptional changes induced by EBN had differential effects on insulin signaling genes in liver and adipose."
KCNQ2 affects Kv7.2
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KCNQ2 inhibits Kv7.2. 1 / 1
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reach
"Deleting Kcnq2 enabled us to investigate directly the role of Kv7.2 in sensory neurons."
KCNQ2 affects KCNQ3-Delta476-498 mutants
| 1
KCNQ2 binds KCNQ3-Delta476-498 mutants. 1 / 1
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"Also, the KCNQ2-I340A and KCNQ3-Delta476-498 mutants strongly interacted with wild-type KCNQ3 and KCNQ2, respectively (Figs. 1 C-D)."
| 1
sparser
"Fitting the data for WT and mutant channels to an activation mechanism with independent PI(4,5)P 2 binding to two Kv7.2 and two Kv7.3 subunits suggests that the two components of the M-channel activation curve correspond to the interaction of PI(4,5)P 2 with the Kv7.3 and Kv7.2 subunits, respectively, that channels can open when only the two Kv7.3 subunits have bound DiC 8 -PI(4,5)P 2 , and that maximum channel opening requires binding to all four subunits."
KCNQ2 affects KCNQ K
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KCNQ2 activates KCNQ K. 1 / 1
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reach
"The mutant Phe304del of KCNQ2 leads to null function of the KCNQ K (+) channel but the mutation does not alter proper channel sorting onto the cell membrane."
KCNQ2 affects KCNQ
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KCNQ2 activates KCNQ. 1 / 1
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reach
"Since expression of exogenous KCNQ2 has been previously shown to increase KCNQ current in hippocampal neurons cultured at 10 DIV when a relatively low level of native KCNQ2/3 channels are present XREF_BIBR, we hypothesized that expression of wild-type KCNQ2 subunits would reduce action potential firing by increasing axonal surface expression of both homomeric KCNQ2 channels and heteromeric channels formed with endogenous KCNQ3 subunits (XREF_FIG)."
KCNQ2 affects IKBKB
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KCNQ2 activates IKBKB. 1 / 1
| 1
reach
"Moreover, EBN upregulated mTOR and Prkcz in the liver and adipose tissue but only caused downregulation of MAPK and Ikbkb in the liver indicating that the transcriptional changes induced by EBN had differential effects on insulin signaling genes in liver and adipose."
KCNQ2 affects IK
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Mutated KCNQ2 inhibits IK. 1 / 1
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reach
"This is the first evidence that a naturally occurring Kcnq2 mutation diminishes the amplitude and function of the native neuronal IK (M), resulting in significantly increased neuronal excitability."
KCNQ2 affects Guo
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KCNQ2 inhibits Guo. 1 / 1
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reach
"Recently, we have found that EBN extract could strongly inhibit infection of influenza viruses in a host-range-independent manner [Guo, C. T.; Takahashi, T.; Bukawa, W.; Takahashi, N.; Yagi, H.; Kato, K.; Hidari, K. I.; Miyamoto, D.; Suzuki, T.; Suzuki, Y. Antiviral Res.2006, 70, 140-146]."
KCNQ2 affects GPD1L
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KCNQ2 activates GPD1L. 1 / 1
| 1
reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects GPC5
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KCNQ2 activates GPC5. 1 / 1
| 1
reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects GCK
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KCNQ2 increases the amount of GCK. 1 / 1
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reach
"EBN intervention was able to upregulate expressions of Gck, Pk, and KCNJ11 in both liver and adipose tissues."
KCNQ2 affects FGF14
| 1
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"FGF14 interacts with KCNQ2 at a site distinct from the FGF14-VGSC interaction surface, thus enabling the bridging of Na V 1.6 and KCNQ2."
KCNQ2 affects EIEE7
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KCNQ2 activates EIEE7. 1 / 1
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"By contrast, EIEE7 is nearly always caused by de novo KCNQ2 missense variants, and characterized by multiple, pharmacoresistant seizures beginning in the first few days of life, burst-suppression pattern or multifocal epileptiform activity at the EEG, and moderate to severe developmental impairment."
KCNQ2 affects CXADR
| 1
KCNQ2 activates CXADR. 1 / 1
| 1
reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects CD4-Q2C to 1
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KCNQ2 inhibits CD4-Q2C to 1. 1 / 1
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reach
"Furthermore, the E810A and D812A mutations in KCNQ2 C-terminus, which disrupt ankyrin-G binding to KCNQ2 XREF_BIBR, XREF_BIBR, XREF_BIBR, reduced the surface " AIS and Axon " ratio of CD4-Q2C to 1, but had no effect on the surface " Axon and Dendrite " ratio (XREF_SUPPLEMENTARY)."
KCNQ2 affects CASQ2
| 1
KCNQ2 activates CASQ2. 1 / 1
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reach
"[XREF_BIBR - XREF_BIBR] Similar scenarios could also be seen in cases of acquired long QT syndrome and ischemic cardiomyopathy, in which rare variants (KCNH2, KCNE1, KCNE2, KCNQ2, SCN5A, and RyR2 in drug induced long QT syndrome and CASQ2, RAB3GAP1, ZNF365, CXADR, GPC5, GPD1L, NOS1AP, and SCN5A in ischemic cardiomyopathy) were associated with higher risk of malignant arrhythmia and SCD."
KCNQ2 affects CALM1
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1 |
hprd
No evidence text available
KCNQ2 affects CA2
| 1
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reach
"The first CaM binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2 +-insensitive CaM mutant bind to KCNQ2."
KCNQ2 affects BFNC2
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KCNQ2 activates BFNC2. 1 / 1
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reach
"Two voltage gated potassium channel subunit genes, KCNQ2 and KCNQ3, have been identified to cause BFNC1 and BFNC2, respectively."
KCNQ2 affects BFNC1
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KCNQ2 activates BFNC1. 1 / 1
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reach
"Two voltage gated potassium channel subunit genes, KCNQ2 and KCNQ3, have been identified to cause BFNC1 and BFNC2, respectively."
KCNQ2 affects AKAP79/150
| 1
KCNQ2 binds AKAP79/150. 1 / 1
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reach
"The KCNQ2 subunit of the M channel binds AKAP79/150, while C-terminal regions of the anchoring protein interact with the m1 muscarinic receptor."
KCNQ2 affects A-kinase-anchoring protein AKAP150
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KCNQ2 binds A-kinase-anchoring protein AKAP150. 1 / 1
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reach
"We show here that rat KCNQ2 can bind directly to the multivalent A-kinase-anchoring protein AKAP150."
KCNQ channel opener affects KCNQ2
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KCNQ channel opener activates KCNQ2. 1 / 1
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reach
"Zinc pyrithione (ZnPy) is a newly identified KCNQ channel opener, which potently activates KCNQ2, KCNQ4, and KCNQ5."
INSM1 affects KCNQ2, and RGS11
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sparser
"Insm1, Rgs11 and Kcnq2 are associated with neuronal/adrenal medulla tissue ( xref , xref , xref ) and expression of Irs1, Atp2b1 and Scn3b are controlled by glucocorticoids ( xref , xref , xref , xref )."
IL6 affects KCNQ2
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IL6 inhibits KCNQ2. 1 / 1
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reach
"The reduced serum IL6 despite lack of any transcriptional effect of EBN on the IL6 gene EBN further supports our hypothesis that EBN may have multiple targets, and that the transcriptional changes observed in this study may only partly explain the antioxidant and anti-inflammatory effects of EBN."
HTN3 affects KCNQ2
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HTN3 activates KCNQ2. 1 / 1
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"RTG is more effective than PB against KA induced seizures in Kcnq2 Y284C/+ and Kcnq2 A306T/+ mice."
HN38 affects KCNQ2
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HN38 inhibits KCNQ2. 1 / 1
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"Consistent with previous reports, we found that HN38 almost completely blocked KCNQ2 channel activity."
HFBF affects KCNQ2
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HFBF inhibits KCNQ2. 1 / 1
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reach
"KCNC3, KCNA6, KCNQ2, KCNE1, KCNN1, and KCTD19 genes encode potassium voltage gated channels and are downregulated by the HFBF (XREF_TABLE)."
GSK3B affects KCNQ2
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GSK3B phosphorylates KCNQ2. 1 / 1
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reach
"Recent studies have shown that both the KCNQ2 channel mutants -- associated with bipolar disorder -- and wild-type KCNQ2 channels are phosphorylated by GSK-3beta in vitro, at a site that requires PKA priming and is dephosphorylated by protein phosphatase 2A (PP2A; also known as calcineurin)."
GS26575 affects KCNQ2
| 1
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reach
"In our studies, KCNQ2 and KCNQ3 channels were inhibited by activation of muscarinic m1, m3, and m5 receptors, but not m2 or m4 receptors."
FSCN1 affects KCNQ2
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FSCN1 decreases the amount of KCNQ2. 1 / 1
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reach
"SNL gradually reduced the mRNA levels of Kcna4, Kcnd2, Kcnq2 and Kcnma1 in the DRG over a 4-week period (XREF_FIG)."
FN1 affects KCNQ2, and laminin
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FN1 binds KCNQ2 and laminin. 1 / 1
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sparser
"In contrast, there was only a slight effect of blocking β1 integrin on hNSPC binding to laminin or fibronectin."
FGF14 affects KCNQ2
| 1
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reach
"FGF14 interacts with KCNQ2 at a site distinct from the FGF14-VGSC interaction surface, thus enabling the bridging of Na V 1.6 and KCNQ2."
CRISPR affects KCNQ2
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CRISPR activates KCNQ2. 1 / 1
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reach
"These observations demonstrated that CRISPR mediated KCNQ2 gene silencing treatment was effective in silencing M-currents in human neurons leading to a predictable lack of functional response to its channel blocker as assessed at both single cell and neuronal network level."
COLEC11 affects GLI2, ID1, KCNQ2, and SHANK2
| 1
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sparser
"Among the non-imprinted genes showing individual DNA methylation changes in the analyzed patients, COLEC11 , SHANK2 , GLI2 and KCNQ2 have been previously associated with ID, brain malformation, and epilepsy."
CDK5 affects KCNQ2
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CDK5 phosphorylates KCNQ2 on S446. 1 / 1
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biopax:phosphositeplus
No evidence text available
CAMK2A affects KCNQ2
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CAMK2A phosphorylates KCNQ2 on S438. 1 / 1
1 |
biopax:phosphositeplus
No evidence text available
CALM1 affects KCNQ2
1 |
1 |
hprd
No evidence text available
CALM affects KCNQ2, and PKC
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CALM binds PKC and KCNQ2. 1 / 1
| 1
sparser
"In conclusion, signaling events that can change the configuration of CaM-KCNQ2 binding, such as elevation of intracellular calcium or PKC phosphorylation, lower KCNQ2 affinity toward PIP2."
CALM affects KCNQ2, KCNQ3, and cooH
| 1
CALM binds KCNQ2, KCNQ3, and cooH. 1 / 1
| 1
sparser
"Using similar biochemical approaches, both papers demonstrated CaM binding to the intracellular COOH-terminal domains of KCNQ2 and KCNQ3 channels, and disruption of binding by mutagenesis of residues at regions similar to those named IQ 1 and IQ 2 in the present study."
CALM affects KCNQ2, and KCNQ3
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CALM binds KCNQ2 and KCNQ3. 1 / 1
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sparser
"Recent studies have shown that calmodulin (CaM) binds to the KCNQ2 and KCNQ3 C termini and may function as an auxiliary channel subunit xref , xref , xref ."
CALM affects KCNQ1, and KCNQ2
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CALM binds KCNQ1 and KCNQ2. 1 / 1
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sparser
"WT and mutant Kv7.1 C-termini and Kv7.2 C-terminus did interact with CaM as assayed by HIS3 induction in the GAL4 based yeast two-hybrid system ( Fig. 4 B) while the negative controls did not produce any signal."
CA2 affects KCNQ2
| 1
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reach
"The first CaM binding motif has a sequence that conforms partially to the consensus IQ motif, but both wild-type CaM and a Ca2 +-insensitive CaM mutant bind to KCNQ2."
BMS-204352 affects KCNQ2
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BMS-204352 activates KCNQ2. 1 / 1
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"However, it has recently been shown that BMS-204352 is also an activator of the KCNQ2 and KCNQ4 channels as well as of the heteromeric KCNQ2 and KCNQ3 and KCNQ3 and KCNQ4 channels (Schroder et al., 2001)."
BL-1249 affects KCNQ2
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BL-1249 inhibits KCNQ2. 1 / 1
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"For example, BL-1249 produces significant inhibition of BK (K Ca 1.1), K v 7.2 (KCNQ2), K v 7.3 (KCNQ3) and Na V 1.7 channels at a concentration of 10muM."
BAG3 affects KCNQ2
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BAG3 activates KCNQ2. 1 / 1
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"Likewise BIS I and BIS IV modulated KCNQ2 channels differently."
Akap5 affects KCNQ2, and KCNQ3
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"The fraction of complexes representing KCNQ2 or KCNQ3 homomers associated with AKAP150 was very low, as was the fraction of KCNQ2/3 heteromers unpaired with AKAP150."
Akap5 affects KCN, and KCNQ2
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KCN binds KCNQ2 and Akap5. 1 / 1
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"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
ARX affects CDKL5, KCNQ2, MECP2, SCN1A, and STXBP1
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SCN1A binds CDKL5, STXBP1, KCNQ2, MECP2, and ARX. 1 / 1
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"Genes associated with early-onset epilepsy, STXBP1 , KCNQ2 , CDKL5 , SCN1A , MECP2 and ARX, and several genes associated with neurometabolic disease including POLG1 and NDUFAF1 were sequenced with no significant variations ."
ARSD affects CHRNA4, and KCNQ2
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"The HAR1A gene is considered an accelerated evolution gene for human brain development with molecular defects of the gene leading to psychotic and disruptive disorders [ xref ]; the genes CHRNA4 and KCNQ2 also deleted have been associated with ASD and epilepsy [ xref , xref ]."
ARFGAP3 affects CHRNA4, and KCNQ2
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"The ARFGAP1, CHRNA4 and KCNQ2 genes have been associated with neurological deficits."
ARAF affects KCNQ2, and KCNQ3
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KCNQ2 binds KCNQ3 and ARAF. 1 / 1
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"Kv7.2 and Kv7.3 subunits are associated with PKs such as PKC through AKAPs [ xref ]."
ANK3 affects KCNQ2, KCNQ3, and voltage-gated potassium channel
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ANK3 binds KCNQ2, KCNQ3, and voltage-gated potassium channel. 1 / 1
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"In line with this role, ANK3 interacts directly with KCNQ2, which is expressed in the brain and forms homomeric and heteromeric voltage-gated potassium channels with another member of the KCNQ family, KCNQ3."
AKAP9 affects Akap5, KCN, and KCNQ2
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KCN binds AKAP9, KCNQ2, and Akap5. 1 / 1
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"EGFR might be tethered to the complex by directly binding to the anchoring protein AKAP9 as shown by the interaction between AKAP150 and the M-type potassium channel, KCNQ2 ( xref )."
AKAP79/150 affects KCNQ2
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KCNQ2 binds AKAP79/150. 1 / 1
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"The KCNQ2 subunit of the M channel binds AKAP79/150, while C-terminal regions of the anchoring protein interact with the m1 muscarinic receptor."
ADP affects KCNQ2
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ADP activates KCNQ2. 1 / 1
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"Increasing the conductance of the KCNQ2 model reduced the ADP considerably (XREF_FIG)."
A1-A3 affects KCNQ2
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A1-A3 activates KCNQ2-W236L. 1 / 1
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"It was observed that compounds A1-A3 failed to stimulate the KCNQ2 (W236L) mutant, indicating that they depend on tryptophan 236 to activate the KCNQ2 channel, like retigabine."
A-kinase-anchoring protein AKAP150 affects KCNQ2
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KCNQ2 binds A-kinase-anchoring protein AKAP150. 1 / 1
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"We show here that rat KCNQ2 can bind directly to the multivalent A-kinase-anchoring protein AKAP150."
5-HT6R affects KCNQ2
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5-HT6R increases the amount of KCNQ2. 1 / 1
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"Interestingly, antagonism of 5-HT6R by SB271046 upregulated the expression of KCNQ2 but not KCNQ3."
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"KCNQ2 and KCNQ3 currents can be increased by intracellular cyclic AMP, an effect that depends on an intact phosphorylation site in the KCNQ2 amino terminus."