Target Information
| Target General Information | Top | |||||
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| Target ID |
T49080
(Former ID: TTDI03338)
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| Target Name |
Voltage-gated potassium channel Kv3.1 (KCNC1)
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| Synonyms |
Voltage-gated potassium channel subunit Kv4; Voltage-gated potassium channel subunit Kv3.1; Potassium voltage-gated channel subfamily C member 1; NGK2
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| Gene Name |
KCNC1
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| Target Type |
Literature-reported target
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| Function |
The channel opens in response to the voltage difference across the membrane, forming a potassium-selective channel through which potassium ions pass in accordance with their electrochemical gradient. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNC2, and possibly other family members as well. Contributes to fire sustained trains of very brief action potentials at high frequency in pallidal neurons. Voltage-gated potassium channel that plays an important role in the rapid repolarization of fast-firing brain neurons.
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| BioChemical Class |
Voltage-gated ion channel
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| UniProt ID | ||||||
| Sequence |
MGQGDESERIVINVGGTRHQTYRSTLRTLPGTRLAWLAEPDAHSHFDYDPRADEFFFDRH
PGVFAHILNYYRTGKLHCPADVCGPLYEEELAFWGIDETDVEPCCWMTYRQHRDAEEALD SFGGAPLDNSADDADADGPGDSGDGEDELEMTKRLALSDSPDGRPGGFWRRWQPRIWALF EDPYSSRYARYVAFASLFFILVSITTFCLETHERFNPIVNKTEIENVRNGTQVRYYREAE TEAFLTYIEGVCVVWFTFEFLMRVIFCPNKVEFIKNSLNIIDFVAILPFYLEVGLSGLSS KAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFA TMIYYAERIGAQPNDPSASEHTHFKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALC ALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPKKKKKHIPRPPQLGSPNYCKSVVNSPH HSTQSDTCPLAQEEILEINRAGRKPLRGMSI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| 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: Colfosceril palmitate | Ligand Info | |||||
| Structure Description | Human voltage-gated potassium channel Kv3.1 (with Zn) | PDB:7PHI | ||||
| Method | Electron microscopy | Resolution | 3.10 Å | Mutation | No | [3] |
| PDB Sequence |
SERIVINVGG
16 TRHQTHRSTL26 RTLPGTRLAW36 LAEPDAHSHF46 DYDPRADEFF56 FDRHPGVFAH 66 ILNYYRTGKL76 HCPADVCGPL86 YEEELAFWGI96 DETDVEPCCW106 MTYRQHRDAE 116 EALDRRWQPR175 IWALFEDPYS185 SRYARYVAFA195 SLFFILVSIT205 TFCLETHERF 215 NPIVNKTYYR237 EAETEAFLTY247 IEGVCVVWFT257 FEFLMRVIFC267 PNKVEFIKNS 277 LNIIDFVAIL287 PFYLEVGLSK301 AAKDVLGFLR311 VVRFVRILRI321 FKLTRHFVGL 331 RVLGHTLRAS341 TNEFLLLIIF351 LALGVLIFAT361 MIYYAERIGA371 QPNDPSASEH 381 THFKNIPIGF391 WWAVVTMTTL401 GYGDMYPQTW411 SGMLVGALCA421 LAGVLTIAMP 431 VPVIVNNFGM441 YYSLAMAKQK451 LPKKKKKHIP461 RPP
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 1-(4-methylphenyl)sulfonyl-N-(1,3-oxazol-2-ylmethyl)pyrrole-3-carboxamide | Ligand Info | |||||
| Structure Description | Ligand-bound human Kv3.1 cryo-EM structure (Lu AG00563) | PDB:7PQU | ||||
| Method | Electron microscopy | Resolution | 3.03 Å | Mutation | No | [4] |
| PDB Sequence |
SERIVINVGG
16 TRHQTYRSTL26 RTLPGTRLAW36 LAEPDAHSHF46 DYDPRADEFF56 FDRHPGVFAH 66 ILNYYRTGKL76 HCPADVCGPL86 YEEELAFWGI96 DETDVEPCCW106 MTYRQHRDAE 116 EALYARYVAF194 ASLFFILVSI204 TTFCLETHER214 FNPETEAFLT246 YIEGVCVVWF 256 TFEFLMRVIF266 CPNKIIDFVA285 ILPFYLEVGL310 RVVRFVRILR320 IFKLTRHFVG 330 LRVLGHTLRA340 STNEFLLLII350 FLALGVLIFA360 TMIYYAERIG370 ASASEHTHFK 385 NIPIGFWWAV395 VTMTTLGYGD405 MYPQTWSGML415 VGALCALAGV425 LTIAMPVPVI 435 VNNFGMYYSL445 AMAKQKLP
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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).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Biological Network Descriptors
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| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 1.42E-07 |
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| Closeness centrality | 1.20E-01 | Radiality | 1.05E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.50E+00 | Topological coefficient | 7.50E-01 | Eccentricity | 16 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| References | Top | |||||
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| REF 1 | Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1. Neuropharmacology. 2001 Sep;41(4):443-53. | |||||
| REF 2 | Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol. 1994 Jun;45(6):1227-34. | |||||
| REF 3 | Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain. Nat Commun. 2022 Jul 15;13(1):4087. | |||||
| REF 4 | Apo and ligand-bound high resolution Cryo-EM structures of the human Kv3.1 channel reveal a novel binding site for positive modulators. PNAS Nexus. 2022 Jun 16;1(3):pgac083. | |||||
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