General Information of This Target
Target ID
BTDT10067
Target Name
Intermediate conductance calcium-activated potassium channel protein 4
Target Bioclass
Transporter and channel
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N.A.
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Potassium channel toxin alpha-KTx 2.1 Dissociation constant
>25 nM
[1], [2], [3], [4]
 Toxin Info    Kappa-stichotoxin-She3a Dissociation constant
0.03 - 30 nM
[5- 20]
 Toxin Info    Potassium channel toxin alpha-KTx 4.8 Dissociation constant
59 nM
[21]
 Toxin Info    Kappa-actitoxin-Bgr1a Dissociation constant
172 nM
[8- 27]
 Toxin Info    ChTX (K27[Orn]) Dissociation constant
3.3 μM
[28]
 Toxin Info    Toxin MeKTx13-3 (D33H) Inhibition rate . [29]
 Toxin Info    Potassium channel toxin alpha-KTx 5.4 Inhibition rate . [30], [31]
 Toxin Info    Defensin BmKDfsin4 Inhibition rate
3.9 %
[32], [33], [34]
 Toxin Info    Defensin BmKDfsin5 Inhibition rate
9.1 %
[32], [35]
 Toxin Info    Potassium channel toxin alpha-KTx 6.2 IC50
1.2 - 2 nM
[36- 48]
 Toxin Info    Potassium channel toxin alpha-KTx 3.7 IC50
225 nM
[49], [50], [51], [52]
 Toxin Info    Potassium channel toxin alpha-KTx 3.2 IC50
1.152 μM
[45- 55]
References
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Ref 2 Synthetic peptides corresponding to the sequence of noxiustoxin indicate that the active site of this K+ channel blocker is located on its amino-terminal portion. J Neural Transm. 1989;77(1):11-20. doi: 10.1007/BF01255815.
Ref 3 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 4 Determination of the three-dimensional solution structure of noxiustoxin: analysis of structural differences with related short-chain scorpion toxins. Biochemistry. 1995 Dec 26;34(51):16563-73. doi: 10.1021/bi00051a004.
Ref 5 Characterization of a potassium channel toxin from the Caribbean Sea anemone Stichodactyla helianthus. Toxicon. 1995 May;33(5):603-13. doi: 10.1016/0041-0101(95)00013-c.
Ref 6 Chemical synthesis and characterization of ShK toxin: a potent potassium channel inhibitor from a sea anemone. Int J Pept Protein Res. 1995 Nov;46(5):354-8. doi: 10.1111/j.1399-3011.1995.tb01068.x.
Ref 7 Identification of three separate binding sites on SHK toxin, a potent inhibitor of voltage-dependent potassium channels in human T-lymphocytes and rat brain. Biochem Biophys Res Commun. 1996 Feb 27;219(3):696-701. doi: 10.1006/bbrc.1996.0297.
Ref 8 Structural conservation of the pores of calcium-activated and voltage-gated potassium channels determined by a sea anemone toxin. J Biol Chem. 1999 Jul 30;274(31):21885-92. doi: 10.1074/jbc.274.31.21885.
Ref 9 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 10 Development of a rational nomenclature for naming peptide and protein toxins from sea anemones. Toxicon. 2012 Sep 15;60(4):539-50. doi: 10.1016/j.toxicon.2012.05.020. Epub 2012 Jun 5.
Ref 11 Defensin-neurotoxin dyad in a basally branching metazoan sea anemone. FEBS J. 2017 Oct;284(19):3320-3338. doi: 10.1111/febs.14194. Epub 2017 Sep 6.
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Ref 13 Sea Anemones: Quiet Achievers in the Field of Peptide Toxins. Toxins (Basel). 2018 Jan 8;10(1):36. doi: 10.3390/toxins10010036.
Ref 14 Solution structure of ShK toxin, a novel potassium channel inhibitor from a sea anemone. Nat Struct Biol. 1996 Apr;3(4):317-20. doi: 10.1038/nsb0496-317.
Ref 15 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 16 Role of disulfide bonds in the structure and potassium channel blocking activity of ShK toxin. Biochemistry. 1999 Nov 2;38(44):14549-58. doi: 10.1021/bi991282m.
Ref 17 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.
Ref 18 Native chemical ligation at Asx-Cys, Glx-Cys: chemical synthesis and high-resolution X-ray structure of ShK toxin by racemic protein crystallography. J Am Chem Soc. 2013 Aug 14;135(32):11911-9. doi: 10.1021/ja4046795. Epub 2013 Aug 6.
Ref 19 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 20 Inversion of the Side-Chain Stereochemistry of Indvidual Thr or Ile Residues in a Protein Molecule: Impact on the Folding, Stability, and Structure of the ShK Toxin. Angew Chem Int Ed Engl. 2017 Mar 13;56(12):3324-3328. doi: 10.1002/anie.201612398. Epub 2017 Feb 14.
Ref 21 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 22 A potassium channel toxin from the secretion of the sea anemone Bunodosoma granulifera. Isolation, amino acid sequence and biological activity. Biochim Biophys Acta. 1993 May 7;1157(1):86-92. doi: 10.1016/0304-4165(93)90082-j.
Ref 23 A potassium-channel toxin from the sea anemone Bunodosoma granulifera, an inhibitor for Kv1 channels. Revision of the amino acid sequence, disulfide-bridge assignment, chemical synthesis, and biological activity. Eur J Biochem. 1997 Feb 15;244(1):192-202. doi: 10.1111/j.1432-1033.1997.00192.x.
Ref 24 Mapping the functional anatomy of BgK on Kv1.1, Kv1.2, and Kv1.3. Clues to design analogs with enhanced selectivity. J Biol Chem. 1999 Dec 10;274(50):35653-61. doi: 10.1074/jbc.274.50.35653.
Ref 25 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 26 Peptide fingerprinting of the neurotoxic fractions isolated from the secretions of sea anemones Stichodactyla helianthus and Bunodosoma granulifera. New members of the APETx-like family identified by a 454 pyrosequencing approach. Peptides. 2012 Mar;34(1):26-38. doi: 10.1016/j.peptides.2011.10.011. Epub 2011 Oct 12.
Ref 27 On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures. J Biol Chem. 1997 Feb 14;272(7):4302-9. doi: 10.1074/jbc.272.7.4302.
Ref 28 Structure-guided transformation of charybdotoxin yields an analog that selectively targets Ca(2+)-activated over voltage-gated K(+) channels. J Biol Chem. 2000 Jan 14;275(2):1201-8. doi: 10.1074/jbc.275.2.1201.
Ref 29 The Scorpion Toxin Analogue BmKTX-D33H as a Potential Kv1.3 Channel-Selective Immunomodulator for Autoimmune Diseases. Toxins (Basel). 2016 Apr 19;8(4):115. doi: 10.3390/toxins8040115.
Ref 30 Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and afterhyperpolarization currents in central neurons. J Biol Chem. 2002 Nov 29;277(48):46101-9. doi: 10.1074/jbc.M206465200. Epub 2002 Sep 17.
Ref 31 Cytotoxicity of recombinant tamapin and related toxin-like peptides on model cell lines. Chem Res Toxicol. 2014 Jun 16;27(6):960-7. doi: 10.1021/tx4004193. Epub 2014 May 12.
Ref 32 The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods. Nat Commun. 2013;4:2602. doi: 10.1038/ncomms3602.
Ref 33 Scorpion Potassium Channel-blocking Defensin Highlights a Functional Link with Neurotoxin. J Biol Chem. 2016 Mar 25;291(13):7097-106. doi: 10.1074/jbc.M115.680611. Epub 2016 Jan 27.
Ref 34 A Scorpion Defensin BmKDfsin4 Inhibits Hepatitis B Virus Replication in Vitro. Toxins (Basel). 2016 Apr 27;8(5):124. doi: 10.3390/toxins8050124.
Ref 35 Ion channel modulation by scorpion hemolymph and its defensin ingredients highlights origin of neurotoxins in telson formed in Paleozoic scorpions. Int J Biol Macromol. 2020 Apr 1;148:351-363. doi: 10.1016/j.ijbiomac.2020.01.133. Epub 2020 Jan 15.
Ref 36 Chemical synthesis and characterization of maurotoxin, a short scorpion toxin with four disulfide bridges that acts on K+ channels. Eur J Biochem. 1996 Dec 15;242(3):491-8. doi: 10.1111/j.1432-1033.1996.0491r.x.
Ref 37 Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom: purification, structure and action on potassium channels. FEBS Lett. 1997 Apr 14;406(3):284-90. doi: 10.1016/s0014-5793(97)00285-8.
Ref 38 Maurotoxin, a four disulfide bridges scorpion toxin acting on K+ channels. Toxicon. 1998 Nov;36(11):1609-11. doi: 10.1016/s0041-0101(98)00153-6.
Ref 39 Mechanisms of maurotoxin action on Shaker potassium channels. Biophys J. 2000 Aug;79(2):776-87. doi: 10.1016/S0006-3495(00)76335-1.
Ref 40 Maurotoxin versus Pi1/HsTx1 scorpion toxins. Toward new insights in the understanding of their distinct disulfide bridge patterns. J Biol Chem. 2000 Dec 15;275(50):39394-402. doi: 10.1074/jbc.M006810200.
Ref 41 Effect of maurotoxin, a four disulfide-bridged toxin from the chactoid scorpion Scorpio maurus, on Shaker K+ channels. J Pept Res. 2000 Jun;55(6):419-27. doi: 10.1034/j.1399-3011.2000.00715.x.
Ref 42 Design and characterization of a highly selective peptide inhibitor of the small conductance calcium-activated K+ channel, SkCa2. J Biol Chem. 2001 Nov 16;276(46):43145-51. doi: 10.1074/jbc.M106981200. Epub 2001 Aug 29.
Ref 43 Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Mol Pharmacol. 2003 Feb;63(2):409-18. doi: 10.1124/mol.63.2.409.
Ref 44 Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins. J Biol Chem. 2004 Dec 31;279(53):55690-6. doi: 10.1074/jbc.M410055200. Epub 2004 Oct 21.
Ref 45 Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX chimera, a new potential blocker for Kv1.2 channel, derived from MTX and AgTx2 scorpion toxins. Protein Sci. 2008 Jan;17(1):107-18. doi: 10.1110/ps.073122908. Epub 2007 Nov 27.
Ref 46 Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus, with high affinity for voltage-gated potassium channels. Proteins. 1997 Nov;29(3):321-33.
Ref 47 Structural and functional consequences of the presence of a fourth disulfide bridge in the scorpion short toxins: solution structure of the potassium channel inhibitor HsTX1. Protein Sci. 1999 Dec;8(12):2672-85. doi: 10.1110/ps.8.12.2672.
Ref 48 Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments ligand affinity. Proteins. 2005 Aug 15;60(3):401-11. doi: 10.1002/prot.20509.
Ref 49 K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom. Biochem J. 2005 Jan 1;385(Pt 1):95-104. doi: 10.1042/BJ20041379.
Ref 50 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 51 Scorpion toxins interact with nicotinic acetylcholine receptors. FEBS Lett. 2019 Oct;593(19):2779-2789. doi: 10.1002/1873-3468.13530. Epub 2019 Jul 18.
Ref 52 Three-dimensional structure of toxin OSK1 from Orthochirus scrobiculosus scorpion venom. Biochemistry. 1997 Feb 11;36(6):1223-32. doi: 10.1021/bi9614390.
Ref 53 Purification and characterization of three inhibitors of voltage-dependent K+ channels from Leiurus quinquestriatus var. hebraeus venom. Biochemistry. 1994 Jun 7;33(22):6834-9. doi: 10.1021/bi00188a012.
Ref 54 A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22211-6. doi: 10.1073/pnas.0910123106. Epub 2009 Dec 10.
Ref 55 Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry. Protein Sci. 1995 Aug;4(8):1478-89. doi: 10.1002/pro.5560040805.
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