General Information of This Target
Target ID
BTDT00176
Target Name
Potassium voltage-gated channel subfamily C member 2 (KCNC2)
Target Bioclass
Transporter and channel
Uniprot ID
Q96PR1
3D Structure
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2D Sequence
3D Structure
Source
Predict by Alphafold2
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Alphafold Parameters: msa_mode: mmseqs2_uniref_env model_type: auto num_recycles: auto
Gene Name
KCNC2
Gene ID
3747
Synonym
Shaw-like potassium channel; Voltage-gated potassium channel Kv3.2
Sequence
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPPGDCLTTAGDKLQPSPPP
LSPPPRAPPLSPGPGGCFEGGAGNCSSRGGRASDHPGGGREFFFDRHPGVFAYVLNYYRT
GKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPG
DDEDLAAKRLGIEDAAGLGGPDGKSGRWRRLQPRMWALFEDPYSSRAARFIAFASLFFIL
VSITTFCLETHEAFNIVKNKTEPVINGTSVVLQYEIETDPALTYVEGVCVVWFTFEFLVR
IVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFK
LTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQ
FKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYY
SLAMAKQKLPRKRKKHIPPAPQASSPTFCKTELNMACNSTQSDTCLGKDNRLLEHNRSVL
SGDDSTGSEPPLSPPERLPIRRSSTRDKNRRGETCFLLTTGDYTCASDGGIRKGYEKSRS
LNNIAGLAGNALRLSPVTSPYNSPCPLRRSRSPIPSIL

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Family
the potassium channel family
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high- threshold voltages and inactivate slowly. Forms tetrameric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 or KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels. Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons. Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation- dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike- evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner.

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Taxonomy ID
9606
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    CboK2 (D2N,K6R,R7K,R8K,N18G,A19R) Inhibition rate . [1]
 Toxin Info    Defensin domain protein Inhibition rate . [2]
 Toxin Info    Potassium channel toxin alpha-KTx 1.15 Inhibition rate . [3]
 Toxin Info    Kappa-LhTx-1 Inhibition rate . [4]
 Toxin Info    Kappa-theraphotoxin-Pg1a Inhibition rate . [5], [6], [7], [8]
 Toxin Info    BmK86-P1 Inhibition rate
4 %
[9]
 Toxin Info    Beta-defensin 3 Inhibition rate
12 %
[10]
 Toxin Info    Defensin domain protein Inhibition rate
16 %
[2]
 Toxin Info    Kappa-stichotoxin-She3a IC50
6 nM
[11]
References
Ref 1 ImKTx96, a peptide blocker of the Kv1.2 ion channel from the venom of the scorpion Isometrus maculates. Peptides. 2020 Jan;123:170172. doi: 10.1016/j.peptides.2019.170172. Epub 2019 Oct 15.
Ref 2 Genome and Transcriptome Sequences Reveal the Specific Parasitism of the Nematophagous Purpureocillium lilacinum 36-1. Front Microbiol. 2016 Jul 19;7:1084. doi: 10.3389/fmicb.2016.01084. eCollection 2016.
Ref 3 Different pharmacological properties between scorpion toxin BmKcug2 and its degraded analogs highlight the diversity of K(+) channel blockers from thermally processed scorpions. Int J Biol Macromol. 2021 May 1;178:143-153. doi: 10.1016/j.ijbiomac.2021.02.155. Epub 2021 Feb 23.
Ref 4 Variation of Two S3b Residues in K(V)4.1-4.3 Channels Underlies Their Different Modulations by Spider Toxin -LhTx-1. Front Pharmacol. 2021 Jun 10;12:692076. doi: 10.3389/fphar.2021.692076. eCollection 2021.
Ref 5 Blockers of the delayed-rectifier potassium current in pancreatic beta-cells enhance glucose-dependent insulin secretion. Diabetes. 2006 Apr;55(4):1034-42. doi: 10.2337/diabetes.55.04.06.db05-0788.
Ref 6 Gating modifier peptides as probes of pancreatic beta-cell physiology. Toxicon. 2007 Feb;49(2):231-8. doi: 10.1016/j.toxicon.2006.09.012. Epub 2006 Sep 23.
Ref 7 A KV2.1 gating modifier binding assay suitable for high throughput screening. Channels (Austin). 2009 Nov;3(6):437-47. doi: 10.4161/chan.3.6.10201.
Ref 8 Solution structure of GxTX-1E, a high-affinity tarantula toxin interacting with voltage sensors in Kv2.1 potassium channels. Biochemistry. 2010 Jun 29;49(25):5134-42. doi: 10.1021/bi100246u.
Ref 9 BmK86-P1, a New Degradation Peptide with Desirable Thermostability and Kv1.2 Channel-Specific Activity from Traditional Chinese Scorpion Medicinal Material. Toxins (Basel). 2021 Aug 30;13(9):610. doi: 10.3390/toxins13090610.
Ref 10 Mouse -Defensin 3, A Defensin Inhibitor of Both Its Endogenous and Exogenous Potassium Channels. Molecules. 2018 Jun 20;23(6):1489. doi: 10.3390/molecules23061489.
Ref 11 Stichodactyla helianthus peptide, a pharmacological tool for studying Kv3.2 channels. Mol Pharmacol. 2005 May;67(5):1513-21. doi: 10.1124/mol.105.011064. Epub 2005 Feb 11.
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