Target Information

General Information of This Target
Target ID
BTDT00204
Target Name
Sodium channel protein type 8 subunit alpha (Scn8a)
Target Bioclass
Transporter and channel
Uniprot ID
Q9WTU3
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
Scn8a
Gene ID
20273
Synonym
Nbna1; Sodium channel protein type VIII subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.6
Sequence
MAARVLAPPGPDSFKPFTPESLANIERRIAESKLKKPPKADGSHREDDEDSKPKPNSDLE
AGKSLPFIYGDIPQGLVAVPLEDFDPYYLTQKTFVVLNRGKTLFRFSATPALYILSPFNL
IRRIAIKILIHSVFSMIIMCTILTNCVFMTFSNPPEWSKNVEYTFTGIYTFESLVKIIAR
GFCIDGFTFLRDPWNWLDFSVIMMAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTI
VGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCVVWPINFNESYLENGTRGF
DWEEYINNKTNFYMVPGMLEPLLCGNSSDAGQCPEGFQCMKAGRNPNYGYTSFDTFSWAF
LALFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFVGSFYLVNLILAVVAMAYEEQNQA
TLEEAEQKEAEFKAMLEQLKKQQEEAQAAAMATSAGTVSEDAIEEEGEDGVGSPRSSSEL
SKLSSKSAKERRNRRKKRKQKELSEGEEKGDPEKVFKSESEDGMRRKAFRLPDNRIGRKF
SIMNQSLLSIPGSPFLSRHNSKSSIFSFRGPGRFRDPGSENEFADDEHSTVEESEGRRDS
LFIPIRARERRSSYSGYSGYSQCSRSSRIFPSLRRSVKRNSTVDCNGVVSLIGPGSHIGR
LLPEATTEVEIKKKGPGSLLVSMEQLASYGRKDRINSIMSVVTNTLVEELEESQRKCPPC
WYKFANTFLIWECHPYWIKLKEIVNLIVMDPFVDLAITICIVLNTLFMAMEHHPMTPQFE
HVLAVGNLVFTGIFTAEMFLKLIAMDPYYYFQEGWNIFDGFIVSLSLMELGLADVEGLSV
LRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKSYK
ECVCKISQECKLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVFMMVMV
IGNLVVLNLFLALLLSSFSADNLAATDDDGEMNNLQISVIRIKKGVAWAKVKVHAFMQAH
FKQREADEVKPLDELYEKKANCIANHTGVDIHRNGDFQKNGNGTTSGIGSSVEKYIIDED
HMSFINNPNLTVRVPIAVGESDFENLNTEDVSSESDPEGSKDKLDDTSSSEGSTIDIKPE
VEEVPVEQPEEYLDPDACFTEGCVQRFKCCQVNIEEGLGKSWWILRKTCFLIVEHNWFET
FIIFMILLSSGALAFEDIYIEQRKTIRTILEYADKVFTYIFILEMLLKWTAYGFVKFFTN
AWCWLDFLIVAVSLVSLIANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNALVG
AIPSIMNVLLVCLIFWLIFSIMGVNLFAGKYHYCFNETSEIRFEIDEVNNKTDCEKLMEG
NNTEIRWKNVKINFDNVGAGYLALLQVATFKGWMDIMYAAVDSRKPDEQPDYEGNIYMYI
YFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNAMKKLGSKKPQK
PIPRPLNKIQGIVFDFVTQQAFDIVIMMLICLNMVTMMVETDTQSKQMENILYWINLVFV
IFFTCECVLKMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVSPTLFRVIRLA
RIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIFSIFGMSNFAYVKHEAGI
DDMFNFETFGNSMICLFQITTSAGWDGLLLPILNRPPDCSLDKEHPGSGFKGDCGNPSVG
IFFFVSYIIISFLIVVNMYIAIILENFSVATEESADPLSEDDFETFYEIWEKFDPDATQF
IEYCKLADFADALEHPLRVPKPNTIELIAMDLPMVSGDRIHCLDILFAFTKRVLGDSGEL
DILRQQMEERFVASNPSKVSYEPITTTLRRKQEEVSAVVLQRAYRGHLARRGFICRKITS
NKLENGGTHREKKESTPSTASLPSYDSVTKPDKEKQQRAEEGRRERAKRQKEVRESKC

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Family
the sodium channel (TC 1.A.1.10) family
Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages, isoform 5 may participate in the control of podosome and invadopodia formation.

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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    N.vectensis toxin 4 Effect . [1]
 Toxin Info    N.vectensis toxin 5 Effect . [1]
 Toxin Info    Potassium channel toxin alpha-KTx 21.1 Inhibition rate . [2- 6]
 Toxin Info    Nemertide alpha-4 Effective concentration 50
27.8 nM
 [7], [8]
 Toxin Info    Nemertide alpha-3 Effective concentration 50
108.4 nM
 [7], [8]
 Toxin Info    Nemertide alpha-3 Effective concentration 50
108.4 nM
 [7], [8]
 Toxin Info    Nemertide alpha-5 Effective concentration 50
132.7 nM
 [7], [8]
 Toxin Info    Nemertide alpha-2 Effective concentration 50
149.2 nM
 [7], [8]
 Toxin Info    Nemertide alpha-7 Effective concentration 50
155.6 nM
 [7], [8]
 Toxin Info    Nemertide alpha-6 Effective concentration 50
215.2 nM
 [7], [8]
 Toxin Info    Nemertide alpha-1 Effective concentration 50
240.4 nM
 [7], [8], [9]
 Toxin Info    Nemertide alpha-1 Effective concentration 50
240.4 nM
 [7], [8], [9]
 Toxin Info    Nemertide alpha-2 Effective concentration 50
1.3618 μM
 [7], [8]
 Toxin Info    Mu-conotoxin PIIIA IC50
100 nM
 [10- 18]
 Toxin Info    Beta/kappa-theraphotoxin-Gi1a IC50
156.39 nM
 [19]
 Toxin Info    Mu-conotoxin SxIIIA IC50
570 nM
 [15- 21]
 Toxin Info    Mu-conotoxin GIIIA IC50
680 nM
 [10- 32]
 Toxin Info    PnCS2 IC50
0.7 ± 0.2 μM
 [33]
 Toxin Info    Mu-conotoxin BuIIIB IC50
1.8 μM
 [13- 35]
 Toxin Info    PnM1 IC50
2.2 ± 1.1 μM
 [33]
 Toxin Info    PnCS4 IC50
4.1 ± 0.6 μM
 [33]
 Toxin Info    PnCS3 IC50
4.5 ± 0.7 μM
 [33]
 Toxin Info    PnM2 IC50
12.3 ± 1.8 μM
 [33]
 Toxin Info    PnM5 IC50
27.4 ± 0.6 μM
 [33]
 Toxin Info    PnM9 IC50
56.3 ± 4.6 μM
 [33]
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 Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions. PLoS One. 2018 Mar 21;13(3):e0193739. doi: 10.1371/journal.pone.0193739. eCollection 2018.
Ref 3 Novel components of Tityus serrulatus venom: A transcriptomic approach. Toxicon. 2021 Jan 15;189:91-104. doi: 10.1016/j.toxicon.2020.11.001. Epub 2020 Nov 10.
Ref 4 Purification and characterization of Ts15, the first member of a new -KTX subfamily from the venom of the Brazilian scorpion Tityus serrulatus. Toxicon. 2011 Jul;58(1):54-61. doi: 10.1016/j.toxicon.2011.05.001. Epub 2011 May 13.
Ref 5 Moving pieces in a venomic puzzle: unveiling post-translationally modified toxins from Tityus serrulatus. J Proteome Res. 2013 Jul 5;12(7):3460-70. doi: 10.1021/pr4003068. Epub 2013 Jun 13.
Ref 6 Influence of post-starvation extraction time and prey-specific diet in Tityus serrulatus scorpion venom composition and hyaluronidase activity. Toxicon. 2014 Nov;90:326-36. doi: 10.1016/j.toxicon.2014.08.064. Epub 2014 Sep 6.
Ref 7 Peptide ion channel toxins from the bootlace worm, the longest animal on Earth. Sci Rep. 2018 Mar 22;8(1):4596. doi: 10.1038/s41598-018-22305-w.
Ref 8 Functional Characterization of the Nemertide Family of Peptide Toxins. J Nat Prod. 2021 Aug 27;84(8):2121-2128. doi: 10.1021/acs.jnatprod.1c00104. Epub 2021 Aug 16.
Ref 9 Compound Heterozygous SCN5A Mutations in Severe Sodium Channelopathy With Brugada Syndrome: A Case Report. Front Cardiovasc Med. 2020 Jul 24;7:117. doi: 10.3389/fcvm.2020.00117. eCollection 2020.
Ref 10 Definition of the M-conotoxin superfamily: characterization of novel peptides from molluscivorous Conus venoms. Biochemistry. 2005 Jun 7;44(22):8176-86. doi: 10.1021/bi047541b.
Ref 11 mu-Conotoxin PIIIA, a new peptide for discriminating among tetrodotoxin-sensitive Na channel subtypes. J Neurosci. 1998 Jun 15;18(12):4473-81. doi: 10.1523/JNEUROSCI.18-12-04473.1998.
Ref 12 Distinction among neuronal subtypes of voltage-activated sodium channels by mu-conotoxin PIIIA. J Neurosci. 2000 Jan 1;20(1):76-80. doi: 10.1523/JNEUROSCI.20-01-00076.2000.
Ref 13 Pruning nature: Biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus. Toxicon. 2009 Jan;53(1):90-8. doi: 10.1016/j.toxicon.2008.10.017. Epub 2008 Nov 20.
Ref 14 A novel -conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors. Br J Pharmacol. 2012 Jul;166(5):1654-68. doi: 10.1111/j.1476-5381.2012.01837.x.
Ref 15 -Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10302-7. doi: 10.1073/pnas.1107027108. Epub 2011 Jun 7.
Ref 16 Co-expression of Na(V) subunits alters the kinetics of inhibition of voltage-gated sodium channels by pore-blocking -conotoxins. Br J Pharmacol. 2013 Apr;168(7):1597-610. doi: 10.1111/bph.12051.
Ref 17 Structurally diverse -conotoxin PIIIA isomers block sodium channel NaV 1.4. Angew Chem Int Ed Engl. 2012 Apr 23;51(17):4058-61. doi: 10.1002/anie.201107011. Epub 2012 Mar 12.
Ref 18 Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels. J Biol Chem. 2002 Jul 26;277(30):27247-55. doi: 10.1074/jbc.M201611200. Epub 2002 May 2.
Ref 19 GiTx1(/-theraphotoxin-Gi1a), a novel toxin from the venom of Brazilian tarantula Grammostola iheringi (Mygalomorphae, Theraphosidae): Isolation, structural assessments and activity on voltage-gated ion channels. Biochimie. 2020 Sep;176:138-149. doi: 10.1016/j.biochi.2020.07.008. Epub 2020 Jul 24.
Ref 20 NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the mu-conotoxin SxIIIA. J Am Chem Soc. 2008 Oct 29;130(43):14280-6. doi: 10.1021/ja804303p. Epub 2008 Oct 3.
Ref 21 - and -subunit composition of voltage-gated sodium channels investigated with -conotoxins and the recently discovered O-conotoxin GVIIJ. J Neurophysiol. 2015 Apr 1;113(7):2289-301. doi: 10.1152/jn.01004.2014. Epub 2015 Jan 28.
Ref 22 Evolution of separate predation- and defence-evoked venoms in carnivorous cone snails. Nat Commun. 2014 Mar 24;5:3521. doi: 10.1038/ncomms4521.
Ref 23 Conus geographus toxins that discriminate between neuronal and muscle sodium channels. J Biol Chem. 1985 Aug 5;260(16):9280-8.
Ref 24 The amino acid sequences of homologous hydroxyproline-containing myotoxins from the marine snail Conus geographus venom. FEBS Lett. 1983 May 8;155(2):277-80. doi: 10.1016/0014-5793(82)80620-0.
Ref 25 Disulfide pairings in geographutoxin I, a peptide neurotoxin from Conus geographus. FEBS Lett. 1990 May 7;264(1):29-32. doi: 10.1016/0014-5793(90)80756-9.
Ref 26 Active site of mu-conotoxin GIIIA, a peptide blocker of muscle sodium channels. J Biol Chem. 1991 Sep 15;266(26):16989-91.
Ref 27 Action of derivatives of mu-conotoxin GIIIA on sodium channels. Single amino acid substitutions in the toxin separately affect association and dissociation rates. Biochemistry. 1992 Sep 8;31(35):8229-38. doi: 10.1021/bi00150a016.
Ref 28 Role of hydroxyprolines in the in vitro oxidative folding and biological activity of conotoxins. Biochemistry. 2008 Feb 12;47(6):1741-51. doi: 10.1021/bi701934m. Epub 2008 Jan 12.
Ref 29 NMR Structure of -Conotoxin GIIIC: Leucine 18 Induces Local Repacking of the N-Terminus Resulting in Reduced Na(V) Channel Potency. Molecules. 2018 Oct 22;23(10):2715. doi: 10.3390/molecules23102715.
Ref 30 Solution structure of mu-conotoxin GIIIA analysed by 2D-NMR and distance geometry calculations. FEBS Lett. 1991 Jan 28;278(2):160-6. doi: 10.1016/0014-5793(91)80107-e.
Ref 31 Tertiary structure of conotoxin GIIIA in aqueous solution. Biochemistry. 1991 Jul 16;30(28):6908-16. doi: 10.1021/bi00242a014.
Ref 32 Structure-activity relationships of mu-conotoxin GIIIA: structure determination of active and inactive sodium channel blocker peptides by NMR and simulated annealing calculations. Biochemistry. 1992 Dec 22;31(50):12577-84. doi: 10.1021/bi00165a006.
Ref 33 Where cone snails and spiders meet: design of small cyclic sodium-channel inhibitors. FASEB J. 2019 Mar;33(3):3693-3703. doi: 10.1096/fj.201801909R. Epub 2018 Dec 3.
Ref 34 Characterization of the Conus bullatus genome and its venom-duct transcriptome. BMC Genomics. 2011 Jan 25;12:60. doi: 10.1186/1471-2164-12-60.
Ref 35 Mammalian neuronal sodium channel blocker -conotoxin BuIIIB has a structured N-terminus that influences potency. ACS Chem Biol. 2013;8(6):1344-51. doi: 10.1021/cb300674x. Epub 2013 Apr 16.
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