Target Information

General Information of This Target
Target ID
BTDT00168
Target Name
Potassium voltage-gated channel subfamily G member 3 (KCNG3)
Target Bioclass
Transporter and channel
Uniprot ID
Q8TAE7
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
KCNG3
Gene ID
170850
Synonym
Voltage-gated potassium channel subunit Kv10.1; Voltage-gated potassium channel subunit Kv6.3
Sequence
MTFGRSGAASVVLNVGGARYSLSRELLKDFPLRRVSRLHGCRSERDVLEVCDDYDRERNE
YFFDRHSEAFGFILLYVRGHGKLRFAPRMCELSFYNEMIYWGLEGAHLEYCCQRRLDDRM
SDTYTFYSADEPGVLGRDEARPGGAEAAPSRRWLERMRRTFEEPTSSLAAQILASVSVVF
VIVSMVVLCASTLPDWRNAAADNRSLDDRSRYSAGPGREPSGIIEAICIGWFTAECIVRF
IVSKNKCEFVKRPLNIIDLLAITPYYISVLMTVFTGENSQLQRAGVTLRVLRMMRIFWVI
KLARHFIGLQTLGLTLKRCYREMVMLLVFICVAMAIFSALSQLLEHGLDLETSNKDFTSI
PAACWWVIISMTTVGYGDMYPITVPGRILGGVCVVSGIVLLALPITFIYHSFVQCYHELK
FRSARYSRSLSTEFLN

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Family
the potassium channel family
Function
Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; this promotes a reduction in the rate of activation and inactivation of the delayed rectifier voltage- gated potassium channel KCNB1.

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Taxonomy ID
9606
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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    N.vectensis toxin 4 Effect . [1]
 Toxin Info    N.vectensis toxin 5 Effect . [1]
 Toxin Info    BeKm1 (R27K) Inhibition rate . [2]
 Toxin Info    Conorfamide-Sr3 Inhibition rate . [3]
 Toxin Info    Toxin PhcrTx2 Inhibition rate . [4]
 Toxin Info    Potassium channel toxin epsilon-KTx 1.2 Inhibition rate . [5]
 Toxin Info    Potassium channel toxin TsTXK-beta Inhibition rate . [6]
 Toxin Info    U-actitoxin-Oulsp1 Inhibition rate . [7]
 Toxin Info    U-actitoxin-Oulsp1 Inhibition rate . [8]
 Toxin Info    U-Asilidin(12)-Dg3b Inhibition rate . [9], [10]
 Toxin Info    Pi-stichotoxin-Hcr5b Inhibition rate . [11]
 Toxin Info    Apamin Inhibition rate . [12- 29]
 Toxin Info    Potassium channel gamma toxin gamma-KTx 1.9 Inhibition rate . [30]
 Toxin Info    BeKm1 Inhibition rate . [2]
 Toxin Info    BeKm1 Inhibition rate . [2]
 Toxin Info    BeKm1 Inhibition rate . [2]
 Toxin Info    Potassium channel toxin alpha-KTx 2.14 Inhibition rate . [31]
 Toxin Info    Potassium channel toxin gamma-KTx 2.1 Inhibition rate . [32]
 Toxin Info    Potassium channel toxin kappa-KTx 1.3 Inhibition rate
6.2 %
 [33]
 Toxin Info    Snake venom serine protease HS114 Inhibition rate
9 %
 [34]
 Toxin Info    Kappa-hefutoxin 2 (C1H,Y2A,R3C,N4Y,C5R,W6N,R7C,E8W,G9R,N10E,D11G,E12N,E13D,T14E,C15E,K16T,E17C,R18K,C19E) Inhibition rate
10.2 %
 [33]
 Toxin Info    Kappa-hefutoxin 2 (C1A,Y2C,R3Y,N4R,C5N,W6C,R7W,E8R,G9E,N10G,D11N,E12D,T14E,C15T,K16C,E17K,R18E,C19R) Inhibition rate
14.1 %
 [33]
 Toxin Info    Potassium channel toxin epsilon-KTx 1.1 Inhibition rate
15 %
 [5]
 Toxin Info    Thrombin-like enzyme gyroxin B1.3 Inhibition rate
58 %
 [35], [36], [37], [34]
 Toxin Info    Thrombin-like enzyme gyroxin B1.3 Inhibition rate
58 %
 [34]
 Toxin Info    Mu/kappa-theraphotoxin-Ap1a IC50
236 nM
 [38]
 Toxin Info    Kappa-theraphotoxin-Aa1a IC50
637 nM
 [38]
 Toxin Info    Kappa-actitoxin-Ael2e IC50
1.1 μM
 [39]
 Toxin Info    Kappa-actitoxin-Ael2e IC50
1.1 μM
 [39]
 Toxin Info    Thrombin-like enzyme collinein-1 IC50
2.5 μM
 [34- 42]
 Toxin Info    Potassium channel toxin kappa-KTx 1.2 IC50
26 μM
 [33- 46]
References
Ref 1 The Birth and Death of Toxins with Distinct Functions: A Case Study in the Sea Anemone Nematostella. Mol Biol Evol. 2019 Sep 1;36(9):2001-2012. doi: 10.1093/molbev/msz132.
Ref 2 Fluorescent analogues of BeKm-1 with high and specific activity against the hERG channel. Toxicon X. 2019 Feb 23;2:100010. doi: 10.1016/j.toxcx.2019.100010. eCollection 2019 Apr.
Ref 3 Conorfamide-Sr3, a structurally novel specific inhibitor of the Shaker K(+) channel. Toxicon. 2017 Nov;138:53-58. doi: 10.1016/j.toxicon.2017.07.024. Epub 2017 Jul 31.
Ref 4 PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer. Toxins (Basel). 2018 Feb 7;10(2):72. doi: 10.3390/toxins10020072.
Ref 5 Structural and Functional Elucidation of Peptide Ts11 Shows Evidence of a Novel Subfamily of Scorpion Venom Toxins. Toxins (Basel). 2016 Sep 30;8(10):288. doi: 10.3390/toxins8100288.
Ref 6 Ts8 scorpion toxin inhibits the Kv4.2 channel and produces nociception in?vivo. Toxicon. 2016 Sep 1;119:244-52. doi: 10.1016/j.toxicon.2016.06.014. Epub 2016 Jun 23.
Ref 7 Sunanda, Punnepalli, et al. "Identification, chemical synthesis, structure, and function of a new KV1 channel blocking peptide from Oulactis sp." Peptide Science 110.4 (2018): e24073.
Ref 8 Structure, folding and stability of a minimal homologue from Anemonia sulcata of the sea anemone potassium channel blocker ShK. Peptides. 2018 Jan;99:169-178. doi: 10.1016/j.peptides.2017.10.001. Epub 2017 Oct 6.
Ref 9 Buzz Kill: Function and Proteomic Composition of Venom from the Giant Assassin Fly Dolopus genitalis (Diptera: Asilidae). Toxins (Basel). 2018 Nov 5;10(11):456. doi: 10.3390/toxins10110456.
Ref 10 Weaponisation 'on the fly': Convergent recruitment of knottin and defensin peptide scaffolds into the venom of predatory assassin flies. Insect Biochem Mol Biol. 2020 Mar;118:103310. doi: 10.1016/j.ibmb.2019.103310. Epub 2019 Dec 21.
Ref 11 A Tale of Toxin Promiscuity: The Versatile Pharmacological Effects of Hcr 1b-2 Sea Anemone Peptide on Voltage-Gated Ion Channels. Mar Drugs. 2022 Feb 17;20(2):147. doi: 10.3390/md20020147.
Ref 12 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 13 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 14 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 15 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 16 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 17 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 18 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 19 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 20 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 21 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 22 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 23 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 24 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 25 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 26 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 27 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 28 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 29 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 30 Isolation, chemical and functional characterization of several new K(+)-channel blocking peptides from the venom of the scorpion Centruroides tecomanus. Toxicon. 2016 Jun 1;115:1-12. doi: 10.1016/j.toxicon.2016.02.017. Epub 2016 Feb 26.
Ref 31 A K? channel blocking peptide from the Cuban scorpion Rhopalurus garridoi. Peptides. 2014 Mar;53:42-7. doi: 10.1016/j.peptides.2013.10.010. Epub 2013 Oct 25.
Ref 32 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 33 Expanding the pharmacological profile of -hefutoxin 1 and analogues: A focus on the inhibitory effect on the oncogenic channel K(v)10.1. Peptides. 2017 Dec;98:43-50. doi: 10.1016/j.peptides.2016.08.008. Epub 2016 Aug 28.
Ref 34 Beyond hemostasis: a snake venom serine protease with potassium channel blocking and potential antitumor activities. Sci Rep. 2020 Mar 11;10(1):4476. doi: 10.1038/s41598-020-61258-x.
Ref 35 Cloning of serine protease cDNAs from Crotalus durissus terrificus venom gland and expression of a functional Gyroxin homologue in COS-7 cells. Toxicon. 2009 Aug;54(2):110-20. doi: 10.1016/j.toxicon.2009.03.022. Epub 2009 Mar 31.
Ref 36 Gyroxin fails to modify in vitro release of labelled dopamine and acetylcholine from rat and mouse striatal tissue. Toxicon. 2001 Jun;39(6):843-53. doi: 10.1016/s0041-0101(00)00222-1.
Ref 37 Gyroxin increases blood-brain barrier permeability to Evans blue dye in mice. Toxicon. 2011 Jan;57(1):162-7. doi: 10.1016/j.toxicon.2010.06.027. Epub 2010 Jul 14.
Ref 38 Novel venom-derived inhibitors of the human EAG channel, a putative antiepileptic drug target. Biochem Pharmacol. 2018 Dec;158:60-72. doi: 10.1016/j.bcp.2018.08.038. Epub 2018 Aug 25.
Ref 39 APETx4, a Novel Sea Anemone Toxin and a Modulator of the Cancer-Relevant Potassium Channel K(V)10.1. Mar Drugs. 2017 Sep 13;15(9):287. doi: 10.3390/md15090287.
Ref 40 Expression of a new serine protease from Crotalus durissus collilineatus venom in Pichia pastoris and functional comparison with the native enzyme. Appl Microbiol Biotechnol. 2015 Dec;99(23):9971-86. doi: 10.1007/s00253-015-6836-2. Epub 2015 Jul 31.
Ref 41 Functional and biological insights of rCollinein-1, a recombinant serine protease from Crotalus durissus collilineatus. J Venom Anim Toxins Incl Trop Dis. 2019 Apr 8;25:e147118. doi: 10.1590/1678-9199-JVATITD-1471-18. eCollection 2019.
Ref 42 Towards toxin PEGylation: The example of rCollinein-1, a snake venom thrombin-like enzyme, as a PEGylated biopharmaceutical prototype. Int J Biol Macromol. 2021 Nov 1;190:564-573. doi: 10.1016/j.ijbiomac.2021.09.004. Epub 2021 Sep 7.
Ref 43 kappa-Hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes with unique structure and function. Importance of the functional diad in potassium channel selectivity. J Biol Chem. 2002 Aug 16;277(33):30040-7. doi: 10.1074/jbc.M111258200. Epub 2002 May 28.
Ref 44 Synthesis and characterization of amino acid deletion analogs of -hefutoxin 1, a scorpion toxin on potassium channels. Toxicon. 2013 Sep;71:25-30. doi: 10.1016/j.toxicon.2013.05.010. Epub 2013 May 29.
Ref 45 Assignment of voltage-gated potassium channel blocking activity to kappa-KTx1.3, a non-toxic homologue of kappa-hefutoxin-1, from Heterometrus spinifer venom. Biochem Pharmacol. 2005 Feb 15;69(4):669-78. doi: 10.1016/j.bcp.2004.10.018. Epub 2004 Dec 29.
Ref 46 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 47 First report on BaltCRP, a cysteine-rich secretory protein (CRISP) from Bothrops alternatus venom: Effects on potassium channels and inflammatory processes. Int J Biol Macromol. 2019 Nov 1;140:556-567. doi: 10.1016/j.ijbiomac.2019.08.108. Epub 2019 Aug 14.
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