Target Information

General Information of This Target
Target ID
BTDT00106
Target Name
Small conductance calcium-activated potassium channel protein 2 (Kcnn2)
Target Bioclass
Transporter and channel
Uniprot ID
P58390
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
140492
Synonym
Sk2; KCa2.2
Sequence
MPIVLVRPTNRTRRLDSTGAGMGPSSHQQQESPLPTITHCAGCTTAWSPCSFNSSDMETP
LQFQRGFFPEQPPPPPRSSHLHCQQQQQSQDKPCAPFAPLPHPHHHPHLAHQQPGSGGSS
PCLRCNSCASSGAPAAGAGAGDNLSLLLRTSSPGGAFRTRTSSPLSGSSCCCCCSSRRGS
QLNVSELTPSSHASALRQQYAQQPASASQYHQCHSLQPATSPTGSLGSLGSGPPLSHHHH
HPHPAHHQHHQPQARRESNPFTEIAMSSCRYNGGVMRPLSNLSSSRRNLQEMDSEAQPLQ
PPASVVGGGGGASSPSAAAAASSSAPEIVVSKPEHNNSNNLALYGTGGGGSTGGGGGGSG
HGSSSGTKSSKKKNQNIGYKLGHRRALFEKRKRLSDYALIFGMFGIVVMVIETELSWGAY
DKASLYSLALKCLISLSTIILLGLIIVYHAREIQLFMVDNGADDWRIAMTYERIFFICLE
ILVCAIHPIPGNYTFTWTARLAFSYAPSTTTADVDIILSIPMFLRLYLIARVMLLHSKLF
TDASSRSIGALNKINFNTRFVMKTLMTICPGTVLLVFSISLWIIAAWTVRACERYHDQQD
VTSNFLGAMWLISITFLSIGYGDMVPNTYCGKGVCLLTGIMGAGCTALVVAVVARKLELT
KAEKHVHNFMMDTQLTKRVKNAAANVLRETWLIYKNTKLVKKIDHAKVRKHQRKFLQAIH
QLRSVKMEQRKLNDQANTLVDLAKTQNIMYDMISDLNERSEDFEKRIVTLETKLETLIGS
IHALPGLISQTIRQQQRDFIETQMENYDKHVSYNAERSRSSSRRRRSSSTAPPTSSESS

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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
10090
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Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Rodentia
Family: Muridae
Genus: Mus
Species: Mus musculus
Toxin Information Related to This Target
                           Toxin Name Activity Data Type Activity Data Reference
 Toxin Info    Apamin IC50
27 - 140 nM
 [1- 20]
References
Ref 1 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 2 [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 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 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 10 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 11 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 12 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 13 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 14 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 15 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 16 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 17 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 18 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 19 [Spatial structure of apamin in solution]. Mol Biol (Mosk). 1991 Jul-Aug;25(4):937-45.
Ref 20 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.
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