General Information of This Target
Target ID
BTDT10052
Target Name
G protein-activated inward rectifier potassium channel 1;G protein-activated inward rectifier potassium channel 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    Kappa-stichotoxin-She3a Inhibition rate . [1- 16]
 Toxin Info    Kunitz-type serine protease inhibitor homolog alpha-dendrotoxin Inhibition rate . [17], [18], [19], [20]
 Toxin Info    Kunitz-type serine protease inhibitor homolog delta-dendrotoxin Inhibition rate . [17- 21]
 Toxin Info    Kunitz-type serine protease inhibitor homolog dendrotoxin I Inhibition rate . [18- 24]
 Toxin Info    Potassium channel toxin alpha-KTx 1.3 Inhibition rate . [25]
 Toxin Info    Potassium channel toxin alpha-KTx 2.1 Inhibition rate . [26], [27], [28]
 Toxin Info    Potassium channel toxin alpha-KTx 2.2 Inhibition rate . [29], [30], [31], [32]
 Toxin Info    Potassium channel toxin alpha-KTx 4.1 Inhibition rate . [29- 37]
 Toxin Info    Potassium channel toxin alpha-KTx 3.1 Inhibition rate . [38- 42]
 Toxin Info    Potassium channel toxin alpha-KTx 3.4 Inhibition rate . [43], [44]
 Toxin Info    Potassium channel toxin alpha-KTx 3.2 Inhibition rate . [38- 46]
 Toxin Info    Apamin Inhibition rate
20 %
[47- 64]
References
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Ref 2 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 3 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 4 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 5 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 6 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 7 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.
Ref 8 Development of a sea anemone toxin as an immunomodulator for therapy of autoimmune diseases. Toxicon. 2012 Mar 15;59(4):529-46. doi: 10.1016/j.toxicon.2011.07.016. Epub 2011 Aug 12.
Ref 9 Sea Anemones: Quiet Achievers in the Field of Peptide Toxins. Toxins (Basel). 2018 Jan 8;10(1):36. doi: 10.3390/toxins10010036.
Ref 10 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 11 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 12 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 13 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 14 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 15 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 16 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.
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Ref 18 Twenty years of dendrotoxins. Toxicon. 2001 Jan;39(1):15-26. doi: 10.1016/s0041-0101(00)00162-8.
Ref 19 Protease inhibitors from marine venomous animals and their counterparts in terrestrial venomous animals. Mar Drugs. 2013 Jun 14;11(6):2069-112. doi: 10.3390/md11062069.
Ref 20 Crystal structure of alpha-dendrotoxin from the green mamba venom and its comparison with the structure of bovine pancreatic trypsin inhibitor. J Mol Biol. 1992 Apr 5;224(3):671-83. doi: 10.1016/0022-2836(92)90552-u.
Ref 21 Energetic and structural interactions between delta-dendrotoxin and a voltage-gated potassium channel. J Mol Biol. 2000 Mar 10;296(5):1283-94. doi: 10.1006/jmbi.2000.3522.
Ref 22 Novel effects of dendrotoxin homologues on subtypes of mammalian Kv1 potassium channels expressed in Xenopus oocytes. FEBS Lett. 1996 Mar 25;383(1-2):26-30. doi: 10.1016/0014-5793(96)00211-6.
Ref 23 Sequence-specific 1H-NMR assignment and secondary structure of black mamba dendrotoxin I, a highly selective blocker of voltage-gated potassium channels. Eur J Biochem. 1993 Feb 1;211(3):813-20. doi: 10.1111/j.1432-1033.1993.tb17613.x.
Ref 24 Proteinase inhibitor homologues as potassium channel blockers. Nat Struct Biol. 1994 Apr;1(4):246-50. doi: 10.1038/nsb0494-246.
Ref 25 Determination of the three-dimensional structure of iberiotoxin in solution by 1H nuclear magnetic resonance spectroscopy. Biochemistry. 1992 Sep 8;31(35):8151-9. doi: 10.1021/bi00150a006.
Ref 26 Charybdotoxin and noxiustoxin, two homologous peptide inhibitors of the K+ (Ca2+) channel. FEBS Lett. 1988 Jan 4;226(2):280-4. doi: 10.1016/0014-5793(88)81439-x.
Ref 27 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 28 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 29 Novel components of Tityus serrulatus venom: A transcriptomic approach. Toxicon. 2021 Jan 15;189:91-104. doi: 10.1016/j.toxicon.2020.11.001. Epub 2020 Nov 10.
Ref 30 Isolation and characterization of Ts19 Fragment II, a new long-chain potassium channel toxin from Tityus serrulatus venom. Peptides. 2016 Jun;80:9-17. doi: 10.1016/j.peptides.2015.06.004. Epub 2015 Jun 25.
Ref 31 Tityus serrulatus venom peptidomics: assessing venom peptide diversity. Toxicon. 2008 Oct;52(5):611-8. doi: 10.1016/j.toxicon.2008.07.010. Epub 2008 Jul 31.
Ref 32 Influence of post-starvation extraction time and prey-specific diet in Tityus serrulatus scorpion venom composition and hyaluronidase activity. Toxicon. 2014 Nov;90:326-36. doi: 10.1016/j.toxicon.2014.08.064. Epub 2014 Sep 6.
Ref 33 Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and unblocks inactivating K+ channels blocked by alpha-dendrotoxin in synaptosomes. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1475-9. doi: 10.1073/pnas.91.4.1475.
Ref 34 Electrophysiological characterization of Ts6 and Ts7, K? channel toxins isolated through an improved Tityus serrulatus venom purification procedure. Toxins (Basel). 2014 Feb 28;6(3):892-913. doi: 10.3390/toxins6030892.
Ref 35 Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel Kv1.3. Br J Pharmacol. 2003 Jul;139(6):1180-6. doi: 10.1038/sj.bjp.0705343.
Ref 36 A common "hot spot" confers hERG blockade activity to alpha-scorpion toxins affecting K+ channels. Biochem Pharmacol. 2008 Sep 15;76(6):805-15. doi: 10.1016/j.bcp.2008.07.008. Epub 2008 Jul 18.
Ref 37 Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A). Biochemistry. 2001 May 22;40(20):5942-53. doi: 10.1021/bi010173g.
Ref 38 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 39 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 40 Kaliotoxin (1-37) shows structural differences with related potassium channel blockers. Biochemistry. 1994 Nov 29;33(47):14256-63. doi: 10.1021/bi00251a038.
Ref 41 A concept for rapid protein-structure determination by solid-state NMR spectroscopy. Angew Chem Int Ed Engl. 2005 Mar 29;44(14):2089-92. doi: 10.1002/anie.200462516.
Ref 42 Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR. Nature. 2006 Apr 13;440(7086):959-62. doi: 10.1038/nature04649.
Ref 43 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 44 Moving pieces in a taxonomic puzzle: venom 2D-LC/MS and data clustering analyses to infer phylogenetic relationships in some scorpions from the Buthidae family (Scorpiones). Toxicon. 2006 May;47(6):628-39. doi: 10.1016/j.toxicon.2006.01.015. Epub 2006 Mar 23.
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 the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry. Protein Sci. 1995 Aug;4(8):1478-89. doi: 10.1002/pro.5560040805.
Ref 47 The precursors of the bee venom constituents apamin and MCD peptide are encoded by two genes in tandem which share the same 3'-exon. J Biol Chem. 1995 May 26;270(21):12704-8. doi: 10.1074/jbc.270.21.12704.
Ref 48 The peptide components of bee venom. Eur J Biochem. 1976 Jan 15;61(2):369-76. doi: 10.1111/j.1432-1033.1976.tb10030.x.
Ref 49 Apamin as a selective blocker of the calcium-dependent potassium channel in neuroblastoma cells: voltage-clamp and biochemical characterization of the toxin receptor. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1308-12. doi: 10.1073/pnas.79.4.1308.
Ref 50 Apamin, a blocker of the calcium-activated potassium channel, induces neurodegeneration of Purkinje cells exclusively. Brain Res. 1997 Dec 19;778(2):405-8. doi: 10.1016/s0006-8993(97)01165-7.
Ref 51 Determinants of apamin and d-tubocurarine block in SK potassium channels. J Biol Chem. 1997 Sep 12;272(37):23195-200. doi: 10.1074/jbc.272.37.23195.
Ref 52 Pharmacological characterization of small-conductance Ca(2+)-activated K(+) channels stably expressed in HEK 293 cells. Br J Pharmacol. 2000 Mar;129(5):991-9. doi: 10.1038/sj.bjp.0703120.
Ref 53 SK3 is an important component of K(+) channels mediating the afterhyperpolarization in cultured rat SCG neurones. J Physiol. 2001 Sep 1;535(Pt 2):323-34. doi: 10.1111/j.1469-7793.2001.00323.x.
Ref 54 Apamin interacts with all subtypes of cloned small-conductance Ca2+-activated K+ channels. Pflugers Arch. 2001 Jan;441(4):544-50. doi: 10.1007/s004240000447.
Ref 55 An amino acid outside the pore region influences apamin sensitivity in small conductance Ca2+-activated K+ channels. J Biol Chem. 2007 Feb 9;282(6):3478-86. doi: 10.1074/jbc.M607213200. Epub 2006 Dec 1.
Ref 56 Apamin reduces neuromuscular transmission by activating inhibitory muscarinic M(2) receptors on motor nerve terminals. Eur J Pharmacol. 2010 Jan 25;626(2-3):239-43. doi: 10.1016/j.ejphar.2009.09.064. Epub 2009 Oct 8.
Ref 57 Allosteric block of KCa2 channels by apamin. J Biol Chem. 2010 Aug 27;285(35):27067-27077. doi: 10.1074/jbc.M110.110072. Epub 2010 Jun 18.
Ref 58 The small neurotoxin apamin blocks not only small conductance Ca(2+) activated K(+) channels (SK type) but also the voltage dependent Kv1.3 channel. Eur Biophys J. 2017 Sep;46(6):517-523. doi: 10.1007/s00249-016-1196-0. Epub 2017 Jan 20.
Ref 59 Apamin inhibits TNF-- and IFN--induced inflammatory cytokines and chemokines via suppressions of NF-B signaling pathway and STAT in human keratinocytes. Pharmacol Rep. 2017 Oct;69(5):1030-1035. doi: 10.1016/j.pharep.2017.04.006. Epub 2017 Apr 18.
Ref 60 Apamin Suppresses LPS-Induced Neuroinflammatory Responses by Regulating SK Channels and TLR4-Mediated Signaling Pathways. Int J Mol Sci. 2020 Jun 17;21(12):4319. doi: 10.3390/ijms21124319.
Ref 61 Apamin from bee venom suppresses inflammation in a murine model of gouty arthritis. J Ethnopharmacol. 2020 Jul 15;257:112860. doi: 10.1016/j.jep.2020.112860. Epub 2020 Apr 11.
Ref 62 Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury. Molecules. 2020 Dec 3;25(23):5717. doi: 10.3390/molecules25235717.
Ref 63 Solution structure of apamin determined by nuclear magnetic resonance and distance geometry. Biochemistry. 1988 Nov 1;27(22):8491-8. doi: 10.1021/bi00422a029.
Ref 64 Binding and toxicity of apamin. Characterization of the active site. Eur J Biochem. 1991 Mar 28;196(3):639-45. doi: 10.1111/j.1432-1033.1991.tb15860.x.
Ref 65 Letter: An anti-inflammatory peptide from bee venom. Nature. 1973 Sep 21;245(5421):163-4. doi: 10.1038/245163a0.
Ref 66 Mast cell degranulating peptide: a multi-functional neurotoxin. J Pharm Pharmacol. 1990 Jul;42(7):457-61. doi: 10.1111/j.2042-7158.1990.tb06595.x.
Ref 67 Engineered specific and high-affinity inhibitor for a subtype of inward-rectifier K+ channels. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10774-8. doi: 10.1073/pnas.0802850105. Epub 2008 Jul 31.
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