Target Information

General Information of This Target
Target ID
BTDT00082
Target Name
Inward rectifier potassium channel 2 (Kcnj2)
Target Bioclass
Transporter and channel
Uniprot ID
P35561
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
Kcnj2
Gene ID
16518
Synonym
Irk1; Inward rectifier K(+) channel Kir2.1; Potassium channel, inwardly rectifying subfamily J member 2
Sequence
MGSVRTNRYSIVSSEEDGMKLATMAVANGFGNGKSKVHTRQQCRSRFVKKDGHCNVQFIN
VGEKGQRYLADIFTTCVDIRWRWMLVIFCLAFVLSWLFFGCVFWLIALLHGDLDTSKVSK
ACVSEVNSFTAAFLFSIETQTTIGYGFRCVTDECPIAVFMVVFQSIVGCIIDAFIIGAVM
AKMAKPKKRNETLVFSHNAVIAMRDGKLCLMWRVGNLRKSHLVEAHVRAQLLKSRITSEG
EYIPLDQIDINVGFDSGIDRIFLVSPITIVHEIDEDSPLYDLSKQDIDNADFEIVVILEG
MVEATAMTTQCRSSYLANEILWGHRYEPVLFEEKHYYKVDYSRFHKTYEVPNTPLCSARD
LAEKKYILSNANSFCYENEVALTSKEEEEDSENGVPESTSTDSPPGIDLHNQASVPLEPR
PLRRESEI

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Family
the inward rectifier-type potassium channel family
Function
Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium.

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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 Dissociation constant
20 μM
 [1- 18]
 Toxin Info    Kunitz-type serine protease inhibitor homolog delta-dendrotoxin Inhibition rate . [19]
 Toxin Info    Potassium channel toxin alpha-KTx 1.2 Inhibition rate . [20]
 Toxin Info    Tertiapin Inhibition rate . [21- 29]
 Toxin Info    U-actitoxin-Avd3n Inhibition rate . [30]
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 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 3 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 4 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 5 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 6 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 7 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 8 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 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 A snake toxin inhibitor of inward rectifier potassium channel ROMK1. Biochemistry. 1998 Oct 20;37(42):14867-74. doi: 10.1021/bi980929k.
Ref 20 Purification, characterization, and synthesis of an inward-rectifier K+ channel inhibitor from scorpion venom. Biochemistry. 1997 Jun 10;36(23):6936-40. doi: 10.1021/bi9702849.
Ref 21 A novel high-affinity inhibitor for inward-rectifier K+ channels. Biochemistry. 1998 Sep 22;37(38):13291-9. doi: 10.1021/bi981178p.
Ref 22 Synthesis of a stable form of tertiapin: a high-affinity inhibitor for inward-rectifier K+ channels. Biochemistry. 1999 Oct 26;38(43):14286-93. doi: 10.1021/bi991205r.
Ref 23 Mechanisms of inward-rectifier K+ channel inhibition by tertiapin-Q. Biochemistry. 1999 Oct 26;38(43):14294-301. doi: 10.1021/bi991206j.
Ref 24 The bee venom peptide tertiapin underlines the role of I(KACh) in acetylcholine-induced atrioventricular blocks. Br J Pharmacol. 2000 Oct;131(3):569-77. doi: 10.1038/sj.bjp.0703611.
Ref 25 Titration of tertiapin-Q inhibition of ROMK1 channels by extracellular protons. Biochemistry. 2001 Mar 27;40(12):3601-5. doi: 10.1021/bi002584n.
Ref 26 Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use-dependent manner. J Pharmacol Exp Ther. 2005 Sep;314(3):1353-61. doi: 10.1124/jpet.105.085928. Epub 2005 Jun 9.
Ref 27 Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation. Pharmacol Res. 2006 Aug;54(2):136-41. doi: 10.1016/j.phrs.2006.03.021. Epub 2006 Apr 1.
Ref 28 Characterization of Kir1.1 channels with the use of a radiolabeled derivative of tertiapin. Biochemistry. 2006 Aug 22;45(33):10129-39. doi: 10.1021/bi060509s.
Ref 29 Solution structure of tertiapin determined using nuclear magnetic resonance and distance geometry. Proteins. 1993 Oct;17(2):124-37. doi: 10.1002/prot.340170203.
Ref 30 AsKC11, a Kunitz Peptide from Anemonia sulcata, Is a Novel Activator of G Protein-Coupled Inward-Rectifier Potassium Channels. Mar Drugs. 2022 Feb 15;20(2):140. doi: 10.3390/md20020140.
Ref 31 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.
Ref 32 Short variable sequence acquired in evolution enables selective inhibition of various inward-rectifier K+ channels. Biochemistry. 2004 Aug 24;43(33):10701-9. doi: 10.1021/bi049125x.
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