PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 33310856-1 2020 Calmodulin (CaM) and phosphatidylinositol 4,5-bisphosphate (PIP2) are potent regulators of the voltage-gated potassium channel KCNQ1 (KV7.1), which conducts the cardiac I Ks current. Phosphatidylinositol 4,5-Diphosphate 21-58 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 127-132 33355140-5 2020 Phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+-calmodulin prevented Kv7.1 inactivation triggered by Ca2+-free external solutions, where Ser182 at the S2-S3 linker relays the calmodulin signal from its inner boundary to the external pore to allow proper channel conduction. Phosphatidylinositol 4,5-Diphosphate 0-37 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 75-80 33355140-5 2020 Phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+-calmodulin prevented Kv7.1 inactivation triggered by Ca2+-free external solutions, where Ser182 at the S2-S3 linker relays the calmodulin signal from its inner boundary to the external pore to allow proper channel conduction. Phosphatidylinositol 4,5-Diphosphate 39-43 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 75-80 33355140-6 2020 Thus, we revealed a unique mechanism of inactivation gating in Kv7.1, exquisitely controlled by external Ca2+ and allosterically coupled by internal PIP2 and Ca2+-calmodulin. Phosphatidylinositol 4,5-Diphosphate 149-153 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 63-68 33310856-1 2020 Calmodulin (CaM) and phosphatidylinositol 4,5-bisphosphate (PIP2) are potent regulators of the voltage-gated potassium channel KCNQ1 (KV7.1), which conducts the cardiac I Ks current. Phosphatidylinositol 4,5-Diphosphate 60-64 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 127-132 33310856-2 2020 Although cryo-electron microscopy structures revealed intricate interactions between the KCNQ1 voltage-sensing domain (VSD), CaM, and PIP2, the functional consequences of these interactions remain unknown. Phosphatidylinositol 4,5-Diphosphate 134-138 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 89-94 33310856-7 2020 Our findings suggest a gating mechanism that integrates PIP2 and CaM in KCNQ1 voltage-dependent activation, yielding insights into how KCNQ1 gains the phenotypes critical for its physiological function. Phosphatidylinositol 4,5-Diphosphate 56-60 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 72-77 33310856-7 2020 Our findings suggest a gating mechanism that integrates PIP2 and CaM in KCNQ1 voltage-dependent activation, yielding insights into how KCNQ1 gains the phenotypes critical for its physiological function. Phosphatidylinositol 4,5-Diphosphate 56-60 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 135-140 28976808-2 2017 The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2) and recently we revealed the competition of PIP2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation. Phosphatidylinositol 4,5-Diphosphate 57-94 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 13-18 32678288-1 2020 KCNQ family K+ channels (KCNQ1-5) in the heart, nerve, epithelium and ear require phosphatidylinositol 4,5-bisphosphate (PIP2) for voltage dependent activation. Phosphatidylinositol 4,5-Diphosphate 82-119 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 25-30 32678288-1 2020 KCNQ family K+ channels (KCNQ1-5) in the heart, nerve, epithelium and ear require phosphatidylinositol 4,5-bisphosphate (PIP2) for voltage dependent activation. Phosphatidylinositol 4,5-Diphosphate 121-125 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 25-30 32678288-2 2020 While membrane lipids are known to regulate voltage sensor domain (VSD) activation and pore opening in voltage dependent gating, PIP2 was found to interact with KCNQ1 and mediate VSD-pore coupling. Phosphatidylinositol 4,5-Diphosphate 129-133 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 161-166 31883792-7 2020 Upon addition, PIP2 occupies a site on KCNQ1 within the inner membrane leaflet, which triggers a large conformational change that leads to dilation of the pore"s gate. Phosphatidylinositol 4,5-Diphosphate 15-19 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 39-44 28976808-2 2017 The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2) and recently we revealed the competition of PIP2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation. Phosphatidylinositol 4,5-Diphosphate 96-100 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 13-18 28976808-2 2017 The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2) and recently we revealed the competition of PIP2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation. Phosphatidylinositol 4,5-Diphosphate 146-150 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 13-18 28976808-2 2017 The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2) and recently we revealed the competition of PIP2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation. Phosphatidylinositol 4,5-Diphosphate 146-150 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 218-223 23861489-4 2013 Here, we show that coupling in Kv7.1 channels requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidylinositol 4,5-Diphosphate 65-102 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 31-36 28575668-4 2017 The conformation corresponds to an "uncoupled," PIP2-free state of KCNQ1, with activated voltage sensors and a closed pore. Phosphatidylinositol 4,5-Diphosphate 48-52 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 67-72 28575668-8 2017 This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP2, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Phosphatidylinositol 4,5-Diphosphate 119-123 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 47-52 28096388-0 2017 Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel. Phosphatidylinositol 4,5-Diphosphate 47-51 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 79-84 28096388-3 2017 The proximal Kv7.1 C terminus (CT) binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2), but the role of CaM in channel function is still unclear, and its possible interaction with PIP2 is unknown. Phosphatidylinositol 4,5-Diphosphate 62-99 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 13-18 28096388-3 2017 The proximal Kv7.1 C terminus (CT) binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2), but the role of CaM in channel function is still unclear, and its possible interaction with PIP2 is unknown. Phosphatidylinositol 4,5-Diphosphate 101-105 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 13-18 28096388-3 2017 The proximal Kv7.1 C terminus (CT) binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP2), but the role of CaM in channel function is still unclear, and its possible interaction with PIP2 is unknown. Phosphatidylinositol 4,5-Diphosphate 200-204 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 13-18 28096388-5 2017 Here, we reveal the competition of PIP2 and the calcified CaM N lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor an LQT mutation. Phosphatidylinositol 4,5-Diphosphate 35-39 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 106-111 28096388-6 2017 Protein pulldown, molecular docking, molecular dynamics simulations, and patch-clamp recordings indicate that residues K526 and K527 in Kv7.1 helix B form a critical site where CaM competes with PIP2 to stabilize the channel open state. Phosphatidylinositol 4,5-Diphosphate 195-199 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 136-141 26469389-5 2015 Guided by the MD results, electrophysiological experiments using KCNQ2, KCNQ1, and hERG channels show that the migration of PIP2 toward the S2-S3 linker controls the deactivation rate of the channel. Phosphatidylinositol 4,5-Diphosphate 124-128 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 72-77 29020060-0 2017 Phosphatidylinositol-4,5-bisphosphate is required for KCNQ1/KCNE1 channel function but not anterograde trafficking. Phosphatidylinositol 4,5-Diphosphate 0-37 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 54-59 29020060-3 2017 It is widely recognised that the KCNQ1/KCNE1 (Q1/E1) channel requires phosphatidylinositol-4,5-bisphosphate (PIP2) binding for function. Phosphatidylinositol 4,5-Diphosphate 70-107 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 33-38 29020060-3 2017 It is widely recognised that the KCNQ1/KCNE1 (Q1/E1) channel requires phosphatidylinositol-4,5-bisphosphate (PIP2) binding for function. Phosphatidylinositol 4,5-Diphosphate 109-113 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 33-38 29020060-4 2017 We previously identified a cluster of basic residues in the proximal C-terminus of KCNQ1 that form a PIP2/phosphoinositide binding site. Phosphatidylinositol 4,5-Diphosphate 101-105 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 83-88 26668384-8 2015 By separating S4 movement and gate opening, either by a mutation or PIP2 depletion, we show that KCNE3 directly affects the S4 movement in KCNQ1. Phosphatidylinositol 4,5-Diphosphate 68-72 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 139-144 25559286-0 2015 PIP2-dependent coupling is prominent in Kv7.1 due to weakened interactions between S4-S5 and S6. Phosphatidylinositol 4,5-Diphosphate 0-4 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 40-45 25559286-4 2015 On the one hand, using molecular dynamics simulations, we identified a Kv7.1 PIP2 binding site that involves residues playing a key role in PIP2-dependent coupling. Phosphatidylinositol 4,5-Diphosphate 77-81 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 71-76 25559286-4 2015 On the one hand, using molecular dynamics simulations, we identified a Kv7.1 PIP2 binding site that involves residues playing a key role in PIP2-dependent coupling. Phosphatidylinositol 4,5-Diphosphate 140-144 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 71-76 25037568-0 2014 Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt I(KS) regulation by PKA and PIP2. Phosphatidylinositol 4,5-Diphosphate 103-107 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 43-48 25037568-8 2014 LQT mutants in KCNQ1 helix C led to a decreased current density and a depolarizing shift of channel activation, mainly arising from impaired phosphatidylinositol-4,5-bisphosphate (PIP2) modulation. Phosphatidylinositol 4,5-Diphosphate 141-178 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 15-20 25037568-8 2014 LQT mutants in KCNQ1 helix C led to a decreased current density and a depolarizing shift of channel activation, mainly arising from impaired phosphatidylinositol-4,5-bisphosphate (PIP2) modulation. Phosphatidylinositol 4,5-Diphosphate 180-184 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 15-20 25037568-10 2014 Thus, KCNQ1 helix C is important for channel modulation by PIP2, whereas the KCNE1 distal C-terminus appears essential for the regulation of IKS by yotiao-mediated PKA phosphorylation. Phosphatidylinositol 4,5-Diphosphate 59-63 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 6-11 24947509-9 2014 To clarify the underlying structural mechanism of PIP2 binding, molecular dynamics simulations of Kv7.1/KCNE1 complexes containing two PIP2 molecules in each subunit at specific sites were performed. Phosphatidylinositol 4,5-Diphosphate 50-54 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 98-103 24947509-9 2014 To clarify the underlying structural mechanism of PIP2 binding, molecular dynamics simulations of Kv7.1/KCNE1 complexes containing two PIP2 molecules in each subunit at specific sites were performed. Phosphatidylinositol 4,5-Diphosphate 135-139 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 98-103 24947509-10 2014 Here, we identified a subset of nine residues participating in the interaction of PIP2 and Kv7.1/KCNE1. Phosphatidylinositol 4,5-Diphosphate 82-86 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 91-96 24904429-4 2014 Recent studies suggest that PIP2 serves as a cofactor to mediate VSD-PGD coupling in KCNQ1 channels. Phosphatidylinositol 4,5-Diphosphate 28-32 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 85-90 23861489-4 2013 Here, we show that coupling in Kv7.1 channels requires the lipid phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidylinositol 4,5-Diphosphate 104-108 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 31-36 15746441-2 2005 We have previously shown that phosphatidylinositol-4,5-bisphosphate (PIP2) regulates the KCNQ1-KCNE1 complex. Phosphatidylinositol 4,5-Diphosphate 30-67 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 89-94 22787448-0 2012 Opposite Effects of the S4-S5 Linker and PIP(2) on Voltage-Gated Channel Function: KCNQ1/KCNE1 and Other Channels. Phosphatidylinositol 4,5-Diphosphate 41-47 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 83-88 22787448-7 2012 As opposed to S4S5(L), the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP(2)), stabilizes KCNQ1 channel in an open state. Phosphatidylinositol 4,5-Diphosphate 45-82 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 104-109 22787448-9 2012 This is highlighted in cases in which an altered regulation of ion channels by PIP(2) leads to channelopathies, as observed for KCNQ1. Phosphatidylinositol 4,5-Diphosphate 79-85 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 128-133 19139916-8 2009 We conclude that tyrphostin A25 inhibits KCNQ1/KCNE1 current by lowering tyrosine phosphorylation on unidentified nonchannel protein(s) that directly or indirectly regulate the open probability of the KCNQ1 pore in a PIP(2)-independent manner. Phosphatidylinositol 4,5-Diphosphate 217-223 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 41-46 19139916-8 2009 We conclude that tyrphostin A25 inhibits KCNQ1/KCNE1 current by lowering tyrosine phosphorylation on unidentified nonchannel protein(s) that directly or indirectly regulate the open probability of the KCNQ1 pore in a PIP(2)-independent manner. Phosphatidylinositol 4,5-Diphosphate 217-223 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 201-206 15746441-2 2005 We have previously shown that phosphatidylinositol-4,5-bisphosphate (PIP2) regulates the KCNQ1-KCNE1 complex. Phosphatidylinositol 4,5-Diphosphate 69-73 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 89-94 15746441-3 2005 In the present study, we show that PIP2 affinity is reduced in three KCNQ1 mutant channels (R243H, R539W, and R555C) associated with the long QT syndrome. Phosphatidylinositol 4,5-Diphosphate 35-39 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 69-74 15746441-7 2005 By using a model that describes the KCNQ1-KCNE1 channel behavior and by fitting the relationship between the kinetics of deactivation and the current amplitude obtained in whole-cell experiments, we estimated the PIP2 binding and dissociation rates on wild-type and mutant channels. Phosphatidylinositol 4,5-Diphosphate 213-217 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 36-41 15746441-10 2005 Altogether, our data suggest that a reduced PIP2 affinity of KCNQ1 mutants can lead to the long QT syndrome. Phosphatidylinositol 4,5-Diphosphate 44-48 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 61-66 15677683-10 2005 Finally, we show that PIP2 hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Phosphatidylinositol 4,5-Diphosphate 22-26 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 121-126 34958868-5 2022 K+ currents through KCNQ1/KCNE1 channels (IKs), which are regulated by both phosphatidylinositol 4,5-bisphosphate (PIP2)-depletion and/or phosphorylation by PKC, were measured as a functional readout of wildtype and mutant alpha1B-AR receptor activity. Phosphatidylinositol 4,5-Diphosphate 76-113 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 20-25 15579540-5 2004 Expressed in COS cells, hKCNE2/hKCNQ1 channels were activated by acidic pH, PIP2, cAMP and purinergic receptor stimulation. Phosphatidylinositol 4,5-Diphosphate 76-80 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 31-37 14532114-0 2003 Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels. Phosphatidylinositol 4,5-Diphosphate 0-37 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 54-59 14532114-0 2003 Phosphatidylinositol-4,5-bisphosphate, PIP2, controls KCNQ1/KCNE1 voltage-gated potassium channels: a functional homology between voltage-gated and inward rectifier K+ channels. Phosphatidylinositol 4,5-Diphosphate 39-43 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 54-59 34958868-5 2022 K+ currents through KCNQ1/KCNE1 channels (IKs), which are regulated by both phosphatidylinositol 4,5-bisphosphate (PIP2)-depletion and/or phosphorylation by PKC, were measured as a functional readout of wildtype and mutant alpha1B-AR receptor activity. Phosphatidylinositol 4,5-Diphosphate 115-119 potassium voltage-gated channel subfamily Q member 1 Homo sapiens 20-25