General Information of This Target
Target ID
BTDT00070
Target Name
Potassium voltage-gated channel subfamily C member 2 (Kcnc2)
Target Bioclass
Transporter and channel
Uniprot ID
P22462
3D Structure
Download
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
246153
Synonym
Potassium channel voltage-gated Shaw-related subfamily C member 2; Shaw-like potassium channel; Voltage-gated potassium channel subunit Kv3.2
Sequence
MGKIENNERVILNVGGTRHETYRSTLKTLPGTRLALLASSEPQGDCLTAAGDKLQPLPPP
LSPPPRPPPLSPVPSGCFEGGAGNCSSHGGNGSDHPGGGREFFFDRHPGVFAYVLNYYRT
GKLHCPADVCGPLFEEELAFWGIDETDVEPCCWMTYRQHRDAEEALDIFETPDLIGGDPG
DDEDLGGKRLGIEDAAGLGGPDGKSGRWRKLQPRMWALFEDPYSSRAARFIAFASLFFIL
VSITTFCLETHEAFNIVKNKTEPVINGTSAVLQYEIETDPALTYVEGVCVVWFTFEFLVR
IVFSPNKLEFIKNLLNIIDFVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFK
LTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERVGAQPNDPSASEHTQ
FKNIPIGFWWAVVTMTTLGYGDMYPQTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYY
SLAMAKQKLPRKRKKHIPPAPLASSPTFCKTELNMACNSTQSDTCLGKENRLLEHNRSVL
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 channels 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 and 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
10116
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Rattus
Species: Rattus norvegicus
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Potassium channel toxin ShK ([pTyr],[AEEA]) Dissociation constant
20 nM
[1]
 Toxin Info    OsK1 (E16A,K20D) Inhibition rate . [2]
 Toxin Info    Potassium channel toxin alpha-KTx 32.1 Inhibition rate . [2]
 Toxin Info    Kunitz-type conkunitzin-S1 Inhibition rate . [3], [4], [5]
 Toxin Info    Mu-theraphotoxin-Pspp1 Inhibition rate . [6]
 Toxin Info    Potassium channel toxin alpha-KTx 3.7 Inhibition rate . [2]
 Toxin Info    Kunitz-type serine protease inhibitor homolog alpha-dendrotoxin Inhibition rate . [7]
 Toxin Info    Potassium channel toxin ShK ([Ppa],[AEEA],M21[Nle]) IC50
4.2 nM
[8]
 Toxin Info    Potassium channel toxin ShK ([pTyr][AEEA]) IC50
20 nM
[8]
 Toxin Info    OsK1 (T,E14K,K18D) IC50
65 nM
[2]
 Toxin Info    OsK1 (V,E14K,K18D) IC50
95 nM
[2]
 Toxin Info    OsK1 (GV,E14K,K18D) IC50
1 μM
[2]
References
Ref 1 Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Mol Pharmacol. 2005 Apr;67(4):1369-81. doi: 10.1124/mol.104.008193. Epub 2005 Jan 21.
Ref 2 Pharmacological profiling of Orthochirus scrobiculosus toxin 1 analogs with a trimmed N-terminal domain. Mol Pharmacol. 2006 Jan;69(1):354-62. doi: 10.1124/mol.105.017210. Epub 2005 Oct 18.
Ref 3 Production of recombinant Conkunitzin-S1 in Escherichia coli. Protein Expr Purif. 2006 Jun;47(2):640-4. doi: 10.1016/j.pep.2006.01.019. Epub 2006 Feb 20.
Ref 4 Conkunitzin-S1 is the first member of a new Kunitz-type neurotoxin family. Structural and functional characterization. J Biol Chem. 2005 Jun 24;280(25):23766-70. doi: 10.1074/jbc.C500064200. Epub 2005 Apr 15.
Ref 5 Structure of conkunitzin-S1, a neurotoxin and Kunitz-fold disulfide variant from cone snail. Acta Crystallogr D Biol Crystallogr. 2006 Sep;62(Pt 9):980-90. doi: 10.1107/S0907444906021123. Epub 2006 Aug 19.
Ref 6 Chemical Synthesis, Proper Folding, Na(v) Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins (Basel). 2019 Jun 21;11(6):367. doi: 10.3390/toxins11060367.
Ref 7 Characterization of a Shaw-related potassium channel family in rat brain. EMBO J. 1992 Jul;11(7):2473-86. doi: 10.1002/j.1460-2075.1992.tb05312.x.
Ref 8 Engineering a stable and selective peptide blocker of the Kv1.3 channel in T lymphocytes. Mol Pharmacol. 2009 Apr;75(4):762-73. doi: 10.1124/mol.108.052704. Epub 2009 Jan 2.
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