Target Information
Target General Information | Top | |||||
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Target ID |
T55916
(Former ID: TTDS00149)
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Target Name |
Voltage-gated potassium channel Kv7.4 (KCNQ4)
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Synonyms |
Voltage-gated potassium channel subunit Kv7.4; Potassium channel alpha subunit KvLQT4; KQT-like 4; KCNQ4
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Gene Name |
KCNQ4
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Target Type |
Literature-reported target
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[1] | ||||
Function |
Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1muscarinic receptors.
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BioChemical Class |
Voltage-gated ion channel
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UniProt ID | ||||||
Sequence |
MAEAPPRRLGLGPPPGDAPRAELVALTAVQSEQGEAGGGGSPRRLGLLGSPLPPGAPLPG
PGSGSGSACGQRSSAAHKRYRRLQNWVYNVLERPRGWAFVYHVFIFLLVFSCLVLSVLST IQEHQELANECLLILEFVMIVVFGLEYIVRVWSAGCCCRYRGWQGRFRFARKPFCVIDFI VFVASVAVIAAGTQGNIFATSALRSMRFLQILRMVRMDRRGGTWKLLGSVVYAHSKELIT AWYIGFLVLIFASFLVYLAEKDANSDFSSYADSLWWGTITLTTIGYGDKTPHTWLGRVLA AGFALLGISFFALPAGILGSGFALKVQEQHRQKHFEKRRMPAANLIQAAWRLYSTDMSRA YLTATWYYYDSILPSFRELALLFEHVQRARNGGLRPLEVRRAPVPDGAPSRYPPVATCHR PGSTSFCPGESSRMGIKDRIRMGSSQRRTGPSKQHLAPPTMPTSPSSEQVGEATSPTKVQ KSWSFNDRTRFRASLRLKPRTSAEDAPSEEVAEEKSYQCELTVDDIMPAVKTVIRSIRIL KFLVAKRKFKETLRPYDVKDVIEQYSAGHLDMLGRIKSLQTRVDQIVGRGPGDRKAREKG DKGPSDAEVVDEISMMGRVVKVEKQVQSIEHKLDLLLGFYSRCLRSGTSASLGAVQVPLF DPDITSDYHSPVDHEDISVSAQTLSISRSVSTNMD Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: (1S,2S,4R)-N-(2,4,6-trimethylphenyl)bicyclo[2.2.1]heptane-2-carboxamid | Ligand Info | |||||
Structure Description | Structure of human KCNQ4-ML213 complex with PIP2 | PDB:7VNP | ||||
Method | Electron microscopy | Resolution | 2.79 Å | Mutation | No | [7] |
PDB Sequence |
SAAHKRYRRL
83 QNWVYNVLER93 PRGWAFVYHV103 FIFLLVFSCL113 VLSVLSTIQE123 HQELANECLL 133 ILEFVMIVVF143 GLEYIVRVWS153 AGCCCRYRGW163 QGRFRFARKP173 FCVIDFIVFV 183 ASVAVIAATS201 ALRSMRFLQI211 LRMVRMDRRG221 GTWKLLGSVV231 YAHSKELITA 241 WYIGFLVLIF251 ASFLVYLAEK261 DANSDFSSYA271 DSLWWGTITL281 TTIGYGDKTP 291 HTWLGRVLAA301 GFALLGISFF311 ALPAGILGSG321 FALKVQEQHR331 QKHFEKRRMP 341 AANLIQAAWR351 LYSTDPAVKT532 VIRSIRILKF542 LVAKRKFKET552 LRPYDVKDVI 562 EQYSAGHLDM572 LGRIKSLQTR582 VD
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
Ligand Name: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propan-2-yl] (8Z)-icosa-5,8,11,14-tetraenoate | Ligand Info | |||||
Structure Description | Structure of human KCNQ4-ML213 complex with PIP2 | PDB:7VNP | ||||
Method | Electron microscopy | Resolution | 2.79 Å | Mutation | No | [7] |
PDB Sequence |
SAAHKRYRRL
83 QNWVYNVLER93 PRGWAFVYHV103 FIFLLVFSCL113 VLSVLSTIQE123 HQELANECLL 133 ILEFVMIVVF143 GLEYIVRVWS153 AGCCCRYRGW163 QGRFRFARKP173 FCVIDFIVFV 183 ASVAVIAATS201 ALRSMRFLQI211 LRMVRMDRRG221 GTWKLLGSVV231 YAHSKELITA 241 WYIGFLVLIF251 ASFLVYLAEK261 DANSDFSSYA271 DSLWWGTITL281 TTIGYGDKTP 291 HTWLGRVLAA301 GFALLGISFF311 ALPAGILGSG321 FALKVQEQHR331 QKHFEKRRMP 341 AANLIQAAWR351 LYSTDPAVKT532 VIRSIRILKF542 LVAKRKFKET552 LRPYDVKDVI 562 EQYSAGHLDM572 LGRIKSLQTR582 VD
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ARG93
3.241
ARG95
2.771
PHE99
3.315
PHE106
2.826
ARG159
3.500
LYS172
2.936
PRO173
4.614
PHE174
4.457
ILE177
3.569
LEU212
3.183
VAL215
3.636
ARG216
4.759
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Human Similarity Proteins
Human Pathway Affiliation
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Cholinergic synapse | hsa04725 | Affiliated Target |
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Class: Organismal Systems => Nervous system | Pathway Hierarchy |
Chemical Structure based Activity Landscape of Target | Top |
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
1 | Cholinergic synapse | |||||
Reactome | [+] 1 Reactome Pathways | + | ||||
1 | Voltage gated Potassium channels | |||||
WikiPathways | [+] 1 WikiPathways | + | ||||
1 | Potassium Channels |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 1 | Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay. Anal Biochem. 2011 Nov 1;418(1):66-72. | |||||
REF 2 | The acrylamide (S)-1 differentially affects Kv7 (KCNQ) potassium channels. Neuropharmacology. 2006 Nov;51(6):1068-77. | |||||
REF 3 | Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate. J Neurosci. 2005 Oct 26;25(43):9825-35. | |||||
REF 4 | KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. Am J Physiol Cell Physiol. 2001 Apr;280(4):C859-66. | |||||
REF 5 | Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol. 2007 May;3(5):287-96. | |||||
REF 6 | Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J Biol Chem. 2008 Nov 7;283(45):30668-76. | |||||
REF 7 | Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel. Neuron. 2022 Jan 19;110(2):237-247.e4. |
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