General Information of This Target
Target ID
BTDT00060
Target Name
Potassium voltage-gated channel subfamily A member 6 (KCNA6)
Target Bioclass
Transporter and channel
Uniprot ID
P17658
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
KCNA6
Gene ID
3742
Synonym
Voltage-gated potassium channel HBK2; Voltage-gated potassium channel subunit Kv1.6
Sequence
MRSEKSLTLAAPGEVRGPEGEQQDAGDFPEAGGGGGCCSSERLVINISGLRFETQLRTLS
LFPDTLLGDPGRRVRFFDPLRNEYFFDRNRPSFDAILYYYQSGGRLRRPVNVPLDIFLEE
IRFYQLGDEALAAFREDEGCLPEGGEDEKPLPSQPFQRQVWLLFEYPESSGPARGIAIVS
VLVILISIVIFCLETLPQFRVDGRGGNNGGVSRVSPVSRGSQEEEEDEDDSYTFHHGITP
GEMGTGGSSSLSTLGGSFFTDPFFLVETLCIVWFTFELLVRFSACPSKPAFFRNIMNIID
LVAIFPYFITLGTELVQQQEQQPASGGGGQNGQQAMSLAILRVIRLVRVFRIFKLSRHSK
GLQILGKTLQASMRELGLLIFFLFIGVILFSSAVYFAEADDDDSLFPSIPDAFWWAVVTM
TTVGYGDMYPMTVGGKIVGSLCAIAGVLTIALPVPVIVSNFNYFYHRETEQEEQGQYTHV
TCGQPAPDLRATDNGLGKPDFPEANRERRPSYLPTPHRAYAEKRMLTEV

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Family
the potassium channel family
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium- selective 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 KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation. Homotetrameric channels display rapid activation and slow inactivation.

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Taxonomy ID
9606
TCDB ID
1.A.1.2.29
        Click to Show/Hide the Complete Species Lineage
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    Bgk (W5Y,Y26F) Dissociation constant
4 pM
[1]
 Toxin Info    Venom basic protease inhibitor 1 homolog (L3R,Q18D,G34R,T36D,R59G) Dissociation constant
0.037 nM
[1]
 Toxin Info    Potassium channel toxin Bgk (W5Y,F6A,Y26F) Dissociation constant
0.07 nM
[1]
 Toxin Info    Potassium channel toxin ShK ([pTyr][AEEA]) Dissociation constant
18 nM
[2]
 Toxin Info    Kappa-actitoxin-Bgr1a Inhibition constant
0.013 nM
[1]
 Toxin Info    Bgk (W5Y,Y26F) Inhibition constant
0.014 nM
[1]
 Toxin Info    Bgk (W5Y,F6A,Y26F) Inhibition constant
0.162 nM
[1]
 Toxin Info    Neurotoxin HsTX1 (R14A) Inhibition rate . [3]
 Toxin Info    Kappa-conotoxin RIIIK Inhibition rate . [4]
 Toxin Info    Potassium channel toxin alpha-KTx 4.8 Inhibition rate . [5]
 Toxin Info    Kunitz-type conkunitzin-S1 Inhibition rate . [6], [7], [8]
 Toxin Info    Potassium channel toxin alpha-KTx 1.15 Inhibition rate
5 %
[9]
 Toxin Info    ChTX (M29I) Inhibition rate
9.6 %
[10]
 Toxin Info    Potassium channel toxin ShK ([Pmp][AEEA],M21[Nle]) Inhibition rate
10 %
[11]
 Toxin Info    BmK86-P1 Inhibition rate
11 %
[12]
 Toxin Info    Potassium channel toxin ShK ([Pmp][AEEA]) Inhibition rate
25 %
[11]
 Toxin Info    Potassium channel toxin ShK (Q16K,37A) Inhibition rate
25 %
[11]
 Toxin Info    Potassium channel toxin ShK (Q16K,M21I,37A) Inhibition rate
25 %
[11]
 Toxin Info    Beta-defensin 3 Inhibition rate
31 %
[13]
 Toxin Info    Kappa-conotoxin SrXIA Inhibition rate
58 %
[14], [15]
 Toxin Info    Kappa-stichotoxin-She3a IC50
0.165 nM
[16]
 Toxin Info    Potassium channel toxin ShK (K22[Dap]) IC50
10.5 nM
[16]
 Toxin Info    ([20kDa-PEG] -(Lys16)-ShK IC50
466 nM
[17]
 Toxin Info    Conorfamide-Sr3 IC50
2.7 μM
[18]
 Toxin Info    Conorfamide-Sr3 IC50
2.7 μM
[19], [18]
 Toxin Info    Kappa-conotoxin RIIIJ IC50
8 μM
[4]
References
Ref 1 Characterization of a novel radiolabeled peptide selective for a subpopulation of voltage-gated potassium channels in mammalian brain. J Biol Chem. 2002 Feb 8;277(6):3886-93. doi: 10.1074/jbc.M109886200. Epub 2001 Nov 13.
Ref 2 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 3 A Fluorescent Peptide Toxin for Selective Visualization of the Voltage-Gated Potassium Channel K(V)1.3. Bioconjug Chem. 2022 Nov 16;33(11):2197-2212. doi: 10.1021/acs.bioconjchem.2c00436. Epub 2022 Nov 4.
Ref 4 Biochemical characterization of kappaM-RIIIJ, a Kv1.2 channel blocker: evaluation of cardioprotective effects of kappaM-conotoxins. J Biol Chem. 2010 May 14;285(20):14882-14889. doi: 10.1074/jbc.M109.068486. Epub 2010 Mar 10.
Ref 5 Characterization and Chemical Synthesis of Cm39 (-KTx 4.8): A Scorpion Toxin That Inhibits Voltage-Gated K(+) Channel K(V)1.2 and Small- and Intermediate-Conductance Ca(2+)-Activated K(+) Channels K(Ca)2.2 and K(Ca)3.1. Toxins (Basel). 2023 Jan 5;15(1):41. doi: 10.3390/toxins15010041.
Ref 6 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 7 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 8 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 9 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 10 Gigolaev, A. M., et al. "KV1. 2-Selective Peptide with High Affinity."?Journal of Evolutionary Biochemistry and Physiology?58.6 (2022): 2048-2057.
Ref 11 Development of highly selective Kv1.3-blocking peptides based on the sea anemone peptide ShK. Mar Drugs. 2015 Jan 16;13(1):529-42. doi: 10.3390/md13010529.
Ref 12 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 13 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 14 I-conotoxins in vermivorous species of the West Atlantic: peptide sr11a from Conus spurius. Peptides. 2007 Jan;28(1):18-23. doi: 10.1016/j.peptides.2006.08.024. Epub 2006 Dec 12.
Ref 15 Peptide sr11a from Conus spurius is a novel peptide blocker for Kv1 potassium channels. Peptides. 2010 Jul;31(7):1287-91. doi: 10.1016/j.peptides.2010.04.007. Epub 2010 Apr 18.
Ref 16 ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide. J Biol Chem. 1998 Dec 4;273(49):32697-707. doi: 10.1074/jbc.273.49.32697.
Ref 17 Pharmaceutical Optimization of Peptide Toxins for Ion Channel Targets: Potent, Selective, and Long-Lived Antagonists of Kv1.3. J Med Chem. 2015 Sep 10;58(17):6784-802. doi: 10.1021/acs.jmedchem.5b00495. Epub 2015 Aug 31.
Ref 18 Studies of Conorfamide-Sr3 on Human Voltage-Gated Kv1 Potassium Channel Subtypes. Mar Drugs. 2020 Aug 13;18(8):425. doi: 10.3390/md18080425.
Ref 19 Conorfamide-Sr3, a structurally novel specific inhibitor of the Shaker K(+) channel. Toxicon. 2017 Nov;138:53-58. doi: 10.1016/j.toxicon.2017.07.024. Epub 2017 Jul 31.
Ref 20 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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