Target Information

General Information of This Target
Target ID
BTDT00199
Target Name
Small conductance calcium-activated potassium channel protein 3 (KCNN3)
Target Bioclass
Transporter and channel
Uniprot ID
Q9UGI6
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
KCNN3
Gene ID
3782
Synonym
K3; KCa2.3
Sequence
MDTSGHFHDSGVGDLDEDPKCPCPSSGDEQQQQQQQQQQQQPPPPAPPAAPQQPLGPSLQ
PQPPQLQQQQQQQQQQQQQQPPHPLSQLAQLQSQPVHPGLLHSSPTAFRAPPSSNSTAIL
HPSSRQGSQLNLNDHLLGHSPSSTATSGPGGGSRHRQASPLVHRRDSNPFTEIAMSSCKY
SGGVMKPLSRLSASRRNLIEAETEGQPLQLFSPSNPPEIVISSREDNHAHQTLLHHPNAT
HNHQHAGTTASSTTFPKANKRKNQNIGYKLGHRRALFEKRKRLSDYALIFGMFGIVVMVI
ETELSWGLYSKDSMFSLALKCLISLSTIILLGLIIAYHTREVQLFVIDNGADDWRIAMTY
ERILYISLEMLVCAIHPIPGEYKFFWTARLAFSYTPSRAEADVDIILSIPMFLRLYLIAR
VMLLHSKLFTDASSRSIGALNKINFNTRFVMKTLMTICPGTVLLVFSISLWIIAAWTVRV
CERYHDQQDVTSNFLGAMWLISITFLSIGYGDMVPHTYCGKGVCLLTGIMGAGCTALVVA
VVARKLELTKAEKHVHNFMMDTQLTKRIKNAAANVLRETWLIYKHTKLLKKIDHAKVRKH
QRKFLQAIHQLRSVKMEQRKLSDQANTLVDLSKMQNVMYDLITELNDRSEDLEKQIGSLE
SKLEHLTASFNSLPLLIADTLRQQQQQLLSAIIEARGVSVAVGTTHTPISDSPIGVSSTS
FPTPYTSSSSC

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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
9606
TCDB ID
1.A.1.16.7
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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    Potassium channel toxin alpha-KTx 5.1 Dissociation constant
1.1 nM
 [1]
 Toxin Info    ScyTx (A1T,M7R,D24V) Dissociation constant
4 nM
 [1]
 Toxin Info    ScyTx (M7L) Dissociation constant
6 nM
 [1]
 Toxin Info    ScyTx (F2V,M7R,D24V) Dissociation constant
9 nM
 [1]
 Toxin Info    ScyTx (A1T,F2V,D24V) Dissociation constant
15 nM
 [1]
 Toxin Info    ScyTx (A1T,F2V,M7R) Dissociation constant
24 nM
 [1]
 Toxin Info    Potassium channel toxin alpha-KTx 5.2 Dissociation constant
25 nM
 [1]
 Toxin Info    ScyTx (R6K) Dissociation constant
36 nM
 [1]
 Toxin Info    ScyTx (R6M,M7R) Dissociation constant
65 nM
 [1]
 Toxin Info    ScyTx (M7K) Dissociation constant
105 nM
 [1]
 Toxin Info    ScyTx (R6L) Dissociation constant
180 nM
 [1]
 Toxin Info    Potassium channel toxin alpha-KTx 4.2 Dissociation constant
197 nM
 [1]
 Toxin Info    Pi1 Dissociation constant
250 nM
 [1]
 Toxin Info    Potassium channel toxin alpha-KTx 6.1 Dissociation constant
330 nM
 [1]
 Toxin Info    ScyTx (M7[DaP]) Dissociation constant
2 μM
 [1]
 Toxin Info    ScyTx (M7[Dab]) Dissociation constant
2.5 μM
 [1]
 Toxin Info    OsK1 (R12P,E16K,K20D) Inhibition rate . [2]
 Toxin Info    OsK1 (E16K) Inhibition rate . [2]
 Toxin Info    Potassium channel toxin alpha-KTx 23.1 Inhibition rate . [3]
 Toxin Info    Potassium channel toxin ShK ([pTyr][AEEA]) Inhibition rate . [4]
 Toxin Info    Toxin MeKTx13-3 (D19K) Inhibition rate . [5]
 Toxin Info    Toxin MeKTx13-3 (K6D,D19K) Inhibition rate . [5]
 Toxin Info    Toxin MeKTx13-3 (K6T,G11R,K15NK18G,M22Y,I28T,N29Y,D33H,T35K,K37Q) Inhibition rate . [6]
 Toxin Info    MTX (C19[Abu],C34[Abu]) Inhibition rate . [7]
 Toxin Info    MTX (G33A) Inhibition rate . [7]
 Toxin Info    MTX (K15Q) Inhibition rate . [7]
 Toxin Info    MTX (K23A) Inhibition rate . [7]
 Toxin Info    MTX (K7A) Inhibition rate . [7]
 Toxin Info    MTX (S2A) Inhibition rate . [7]
 Toxin Info    MTX (S6A) Inhibition rate . [7]
 Toxin Info    MTX (T4A) Inhibition rate . [7]
 Toxin Info    MTX (Y10A) Inhibition rate . [7]
 Toxin Info    MTX (Y32A) Inhibition rate . [7]
 Toxin Info    Potassium channel toxin alpha-KTx 8.1 Inhibition rate . [1]
 Toxin Info    Potassium channel toxin alpha-KTx 3.7 Inhibition rate . [2]
 Toxin Info    Defensin domain protein Inhibition rate . [8]
 Toxin Info    Potassium channel toxin alpha-KTx 6.2 Inhibition rate . [1]
 Toxin Info    Beta-defensin 103 Inhibition rate . [9]
 Toxin Info    Beta-defensin 104 Inhibition rate . [9]
 Toxin Info    OsK1 (E16K,K20D) Inhibition rate . [2]
 Toxin Info    OsK1 (E16K,K20D) Inhibition rate . [2]
 Toxin Info    [D20]- OsK1 Inhibition rate . [2]
 Toxin Info    Fungal defensin plectasin Inhibition rate
6 %
 [10]
 Toxin Info    Defensin BmKDfsin4 Inhibition rate
7 %
 [11]
 Toxin Info    Defensin domain protein Inhibition rate
7 %
 [8]
 Toxin Info    Potassium ion channel blocker P05 (N4R,S14R) Inhibition rate
8.5 %
 [12]
 Toxin Info    Beta-defensin 1 Inhibition rate
9 %
 [13]
 Toxin Info    Potassium ion channel blocker P05 (N4R,L15R) Inhibition rate
10.7 %
 [12]
 Toxin Info    Kunitz-type serine protease inhibitor Hg1 Inhibition rate
20 %
 [14]
 Toxin Info    Potassium ion channel blocker P05 (S14R) Inhibition rate
20.5 %
 [12]
 Toxin Info    Potassium channel toxin alpha-KTx J123 Inhibition rate
27 %
 [15]
 Toxin Info    Potassium ion channel blocker P05 (L15R) Inhibition rate
30.5 %
 [12]
 Toxin Info    Defensin BmKDfsin5 Inhibition rate
46 %
 [16]
 Toxin Info    Defensin BmKDfsin3 Inhibition rate
88 %
 [16], [17]
 Toxin Info    Apamin IC50
0.6 - 4 nM
 [18- 37]
 Toxin Info    Apamin IC50
2.3 nM
 [18- 37]
 Toxin Info    Leiurotoxin I-like toxin P05 (R5K,Q8E,E26K) IC50
100 nM
 [38]
References
Ref 1 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 2 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 3 Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells. Mol Pharmacol. 2012 Sep;82(3):372-82. doi: 10.1124/mol.112.078006. Epub 2012 May 23.
Ref 4 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 5 Toxin acidic residue evolutionary function-guided design of de novo peptide drugs for the immunotherapeutic target, the Kv1.3 channel. Sci Rep. 2015 May 8;5:9881. doi: 10.1038/srep09881.
Ref 6 Engineering a peptide inhibitor towards the KCNQ1/KCNE1 potassium channel (IKs). Peptides. 2015 Sep;71:77-83. doi: 10.1016/j.peptides.2015.07.002. Epub 2015 Jul 15.
Ref 7 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 8 Genome and Transcriptome Sequences Reveal the Specific Parasitism of the Nematophagous Purpureocillium lilacinum 36-1. Front Microbiol. 2016 Jul 19;7:1084. doi: 10.3389/fmicb.2016.01084. eCollection 2016.
Ref 9 Pharmacological characterization of human beta-defensins 3 and 4 on potassium channels: Evidence of diversity in beta-defensin-potassium channel interactions. Peptides. 2018 Oct;108:14-18. doi: 10.1016/j.peptides.2018.08.005. Epub 2018 Aug 16.
Ref 10 Plectasin, first animal toxin-like fungal defensin blocking potassium channels through recognizing channel pore region. Toxins (Basel). 2015 Jan 5;7(1):34-42. doi: 10.3390/toxins7010034.
Ref 11 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 12 Two conserved arginine residues from the SK3 potassium channel outer vestibule control selectivity of recognition by scorpion toxins. J Biol Chem. 2013 May 3;288(18):12544-53. doi: 10.1074/jbc.M112.433888. Epub 2013 Mar 19.
Ref 13 Human beta-defensin 1, a new animal toxin-like blocker of potassium channel. Toxicon. 2016 Apr;113:1-6. doi: 10.1016/j.toxicon.2016.02.007. Epub 2016 Feb 5.
Ref 14 Hg1, novel peptide inhibitor specific for Kv1.3 channels from first scorpion Kunitz-type potassium channel toxin family. J Biol Chem. 2012 Apr 20;287(17):13813-21. doi: 10.1074/jbc.M112.343996. Epub 2012 Feb 21.
Ref 15 Characterization of a new Kv1.3 channel-specific blocker, J123, from the scorpion Buthus martensii Karsch. Peptides. 2008 Sep;29(9):1514-20. doi: 10.1016/j.peptides.2008.04.021. Epub 2008 May 13.
Ref 16 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 17 The genome of Mesobuthus martensii reveals a unique adaptation model of arthropods. Nat Commun. 2013;4:2602. doi: 10.1038/ncomms3602.
Ref 18 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 19 [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 20 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 21 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 22 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 23 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 24 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 25 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 26 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 27 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 28 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 29 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 30 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 31 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 32 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 33 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 34 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 35 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 36 [Spatial structure of apamin in solution]. Mol Biol (Mosk). 1991 Jul-Aug;25(4):937-45.
Ref 37 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 38 Protein-protein recognition control by modulating electrostatic interactions. J Proteome Res. 2010 Jun 4;9(6):3118-25. doi: 10.1021/pr100027k.
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