Target Information

General Information of This Target
Target ID
BTDT00112
Target Name
Small conductance calcium-activated potassium channel protein 2 (Kcnn2)
Target Bioclass
Transporter and channel
Uniprot ID
P70604
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
Kcnn2
Gene ID
54262
Synonym
KCa2.2
Sequence
MSSCRYNGGVMRPLSNLSSSRRNLHEMDSEAQPLQPPASVVGGGGGASSPSAAAAASSSA
PEIVVSKPEHNNSNNLALYGTGGGGSTGGGGGGGGGGGGSGHGSSSGTKSSKKKNQNIGY
KLGHRRALFEKRKRLSDYALIFGMFGIVVMVIETELSWGAYDKASLYSLALKCLISLSTI
ILLGLIIVYHAREIQLFMVDNGADDWRIAMTYERIFFICLEILVCAIHPIPGNYTFTWTA
RLAFSYAPSTTTADVDIILSIPMFLRLYLIARVMLLHSKLFTDASSRSIGALNKINFNTR
FVMKTLMTICPGTVLLVFSISLWIIAAWTVRACERYHDQQDVTSNFLGAMWLISITFLSI
GYGDMVPNTYCGKGVCLLTGIMGAGCTALVVAVVARKLELTKAEKHVHNFMMDTQLTKRV
KNAAANVLRETWLIYKNTKLVKKIDHAKVRKHQRKFLQAIHQLRSVKMEQRKLNDQANTL
VDLAKTQNIMYDMISDLNERSEDFEKRIVTLETKLETLIGSIHALPGLISQTIRQQQRDF
IETQMENYDKHVTYNAERSRSSSRRRRSSSTAPPTSSESS

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Family
the potassium channel KCNN family
Function
Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization.

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Taxonomy ID
10116
        Click to Show/Hide the Complete Species Lineage
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    Apamine Dissociation constant
4 pM
 [1]
 Toxin Info    Apamin Dissociation constant
4 pM
 [1- 18]
 Toxin Info    Apamine Dissociation constant
6 pM
 [19]
 Toxin Info    Apamin Dissociation constant
0.012 nM
 [1- 18]
 Toxin Info    Potassium channel toxin alpha-KTx 8.1 Dissociation constant
100 nM
 [20], [21]
 Toxin Info    Potassium channel toxin alpha-KTx 14.4 Dissociation constant
720 nM
 [22]
 Toxin Info    OsK1 (K20D) Inhibition rate . [23]
 Toxin Info    OsK1 (E16K,K20D,T36Y) Inhibition rate . [23]
 Toxin Info    BoiTx1 Inhibition rate . [23]
 Toxin Info    Potassium channel toxin alpha-KTx 6.3 Inhibition rate . [24]
 Toxin Info    Potassium channel toxin gamma-KTx 2.1 Inhibition rate . [25- 34]
 Toxin Info    Potassium channel toxin gamma-KTx 2.1 Inhibition rate . [25]
 Toxin Info    Potassium channel toxin alpha-KTx 3.7 Inhibition rate . [23]
 Toxin Info    OsK1 (E16K,K20D) Inhibition rate . [23]
 Toxin Info    OsK1 (E16K,K20D) Inhibition rate . [23]
 Toxin Info    Potassium channel toxin alpha-KTx 6.3 Inhibition rate . [35]
 Toxin Info    Potassium channel toxin alpha-KTx 8.2 Inhibition rate
4 %
 [36]
 Toxin Info    Potassium channel toxin alpha-KTx 9.1 Inhibition rate
12 %
 [36]
 Toxin Info    Potassium channel toxin alpha-KTx 9.2 Inhibition rate
42 %
 [36]
 Toxin Info    Potassium channel toxin alpha-KTx 19.1 Inhibition rate
62 %
 [37]
 Toxin Info    ScyTx (M7R) IC50
8 pM
 [38]
 Toxin Info    Apamin IC50
0.024 nM
 [1- 18]
 Toxin Info    Potassium channel toxin alpha-KTx 5.4 IC50
0.024 nM
 [39], [40]
 Toxin Info    ScyTx (M7R) IC50
0.08 nM
 [38]
 Toxin Info    Apamin IC50
0.088 nM
 [1- 18]
 Toxin Info    ScyTx IC50
0.4 nM
 [38]
 Toxin Info    ScyTx (I22M,D24K,E27R) IC50
0.6 nM
 [38]
 Toxin Info    Potassium channel toxin alpha-KTx 6.2 IC50
5 nM
 [21- 51]
 Toxin Info    Ts9 (K19A) IC50
7.9 nM
 [52]
 Toxin Info    Ts9 (K18A) IC50
8.9 nM
 [52]
 Toxin Info    Pi1 (Y33[pTyr]) IC50
10 nM
 [53]
 Toxin Info    ScyTx (L6R) IC50
20 nM
 [38]
 Toxin Info    Apamin IC50
27 - 140 nM
 [1- 55]
 Toxin Info    Pi1 (K24A,Y33A) IC50
30 nM
 [53]
 Toxin Info    Ts9 (R9A) IC50
40 nM
 [52]
 Toxin Info    MTX (K15Q) IC50
98 nM
 [45]
 Toxin Info    Pi1 (C20[Abu],[Abu]) IC50
112 nM
 [24]
 Toxin Info    MTX (G33A) IC50
395 nM
 [45]
 Toxin Info    Ts9 (R6A) IC50
500 nM
 [52]
 Toxin Info    Potassium channel toxin alpha-KTx 6.4 IC50
500 nM
 [56], [57], [58]
 Toxin Info    Potassium channel toxin alpha-KTx 5.3 IC50
920 nM
 [36- 61]
 Toxin Info    Leiurotoxin I-like toxin P05 (R5K,I21M,G22N,V23G) IC50
2.2 μM
 [60]
 Toxin Info    Toxin II.10.4[T7P,D9Q) IC50
4.8 μM
 [62]
 Toxin Info    Potassium channel toxin alpha-KTx 10.1 IC50
7.2 μM
 [63], [62]
References
Ref 1 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 2 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 3 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 4 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 5 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 6 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 7 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 8 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 9 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 10 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 11 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 12 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 13 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 14 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 15 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 16 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 17 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 18 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 19 Characterisation of [(125)I]-apamin binding sites in rat brain membranes with HE293 cells transfected with SK channel subtypes. Neuropharmacology. 2001 Sep;41(3):341-50. doi: 10.1016/s0028-3908(01)00067-3.
Ref 20 Characterization of PO1, a new peptide ligand of the apamin-sensitive Ca2+ activated K+ channel. Int J Pept Protein Res. 1996 Dec;48(6):514-21. doi: 10.1111/j.1399-3011.1996.tb00870.x.
Ref 21 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 22 A novel scorpion toxin blocking small conductance Ca2+ activated K+ channel. Toxicon. 2004 Jun 15;43(8):961-71. doi: 10.1016/j.toxicon.2004.01.018.
Ref 23 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 24 The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily. Proteins. 2005 Dec 1;61(4):1010-23. doi: 10.1002/prot.20681.
Ref 25 An ERG channel inhibitor from the scorpion Buthus eupeus. J Biol Chem. 2001 Mar 30;276(13):9868-76. doi: 10.1074/jbc.M005973200. Epub 2001 Jan 2.
Ref 26 M-type K+ current inhibition by a toxin fron the scorpion Buthus eupeus. FEBS Lett. 1996 Apr 22;384(3):277-80. doi: 10.1016/0014-5793(96)00333-x.
Ref 27 BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but the mechanism of action with ErgTx1. Biophys J. 2003 May;84(5):3022-36. doi: 10.1016/S0006-3495(03)70028-9.
Ref 28 Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm-1 scorpion toxin. FEBS Lett. 2003 Jul 17;547(1-3):20-6. doi: 10.1016/s0014-5793(03)00662-8.
Ref 29 Unique interaction of scorpion toxins with the hERG channel. J Mol Recognit. 2004 May-Jun;17(3):209-17. doi: 10.1002/jmr.667.
Ref 30 Species diversity and peptide toxins blocking selectivity of ether-a-go-go-related gene subfamily K+ channels in the central nervous system. Mol Pharmacol. 2006 May;69(5):1673-83. doi: 10.1124/mol.105.019729. Epub 2006 Feb 23.
Ref 31 BeKm-1, a peptide inhibitor of human ether-a-go-go-related gene potassium currents, prolongs QTc intervals in isolated rabbit heart. J Pharmacol Exp Ther. 2011 Apr;337(1):2-8. doi: 10.1124/jpet.110.176883. Epub 2010 Dec 23.
Ref 32 A large number of novel Ergtoxin-like genes and ERG K+-channels blocking peptides from scorpions of the genus Centruroides. FEBS Lett. 2002 Dec 4;532(1-2):121-6. doi: 10.1016/s0014-5793(02)03652-9.
Ref 33 Interaction simulation of hERG K+ channel with its specific BeKm-1 peptide: insights into the selectivity of molecular recognition. J Proteome Res. 2007 Feb;6(2):611-20. doi: 10.1021/pr060368g.
Ref 34 New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1. J Biol Chem. 2002 Nov 8;277(45):43104-9. doi: 10.1074/jbc.M204083200. Epub 2002 Jul 31.
Ref 35 A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom. Biochem J. 1997 Nov 15;328 ( Pt 1)(Pt 1):321-7. doi: 10.1042/bj3280321.
Ref 36 Characterization of four toxins from Buthus martensi scorpion venom, which act on apamin-sensitive Ca2+-activated K+ channels. Eur J Biochem. 1997 Apr 15;245(2):457-64. doi: 10.1111/j.1432-1033.1997.00457.x.
Ref 37 BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch. J Biol Chem. 2004 Aug 13;279(33):34562-9. doi: 10.1074/jbc.M312798200. Epub 2004 Jun 3.
Ref 38 Leiurotoxin I, a scorpion toxin specific for Ca(2+)-activated K+ channels. Structure-activity analysis using synthetic analogs. Int J Pept Protein Res. 1994 May;43(5):486-95. doi: 10.1111/j.1399-3011.1994.tb00548.x.
Ref 39 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 40 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 41 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 42 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 43 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 44 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 45 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 46 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 47 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 48 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 49 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 50 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 51 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 52 Chemical synthesis and structure-activity relationships of Ts kappa, a novel scorpion toxin acting on apamin-sensitive SK channel. J Pept Res. 1999 Nov;54(5):369-76. doi: 10.1034/j.1399-3011.1999.00107.x.
Ref 53 The 'functional' dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels. Biochem J. 2004 Jan 1;377(Pt 1):25-36. doi: 10.1042/BJ20030115.
Ref 54 [Sequence analysis of bee venom neurotoxin (apamine) from its tryptic and chymotryptic cleavage products]. Hoppe Seylers Z Physiol Chem. 1967 Jun;348(6):737-8.
Ref 55 [Spatial structure of apamin in solution]. Mol Biol (Mosk). 1991 Jul-Aug;25(4):937-45.
Ref 56 Two similar peptides from the venom of the scorpion Pandinus imperator, one highly effective blocker and the other inactive on K+ channels. Toxicon. 1998 May;36(5):759-70. doi: 10.1016/s0041-0101(97)00163-3.
Ref 57 Synthesis and characterization of Pi4, a scorpion toxin from Pandinus imperator that acts on K+ channels. Eur J Biochem. 2003 Sep;270(17):3583-92. doi: 10.1046/j.1432-1033.2003.03743.x.
Ref 58 Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels. Protein Sci. 2003 Sep;12(9):1844-54. doi: 10.1110/ps.03186703.
Ref 59 Genomic organization of three neurotoxins active on small conductance Ca2+-activated potassium channels from the scorpion Buthus martensi Karsch. FEBS Lett. 1999 Jun 11;452(3):360-4. doi: 10.1016/s0014-5793(99)00651-1.
Ref 60 Gene expression, mutation, and structure-function relationship of scorpion toxin BmP05 active on SK(Ca) channels. Biochemistry. 2002 Feb 26;41(8):2844-9. doi: 10.1021/bi011367z.
Ref 61 Screening, large-scale production and structure-based classification of cystine-dense peptides. Nat Struct Mol Biol. 2018 Mar;25(3):270-278. doi: 10.1038/s41594-018-0033-9. Epub 2018 Feb 26.
Ref 62 Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels. Biochem J. 2004 Jan 1;377(Pt 1):37-49. doi: 10.1042/BJ20030977.
Ref 63 Cobatoxins 1 and 2 from Centruroides noxius Hoffmann constitute a subfamily of potassium-channel-blocking scorpion toxins. Eur J Biochem. 1998 Jun 15;254(3):468-79. doi: 10.1046/j.1432-1327.1998.2540468.x.
Ref 64 Recombinant and chemical derivatives of apamin. Implication of post-transcriptional C-terminal amidation of apamin in biological activity. Eur J Biochem. 1995 Aug 1;231(3):544-50. doi: 10.1111/j.1432-1033.1995.tb20730.x.
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