Target Information

General Information of This Target
Target ID
BTDT00203
Target Name
Sodium channel protein type 8 subunit alpha (SCN8A)
Target Bioclass
Transporter and channel
Uniprot ID
Q9UQD0
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
SCN8A
Gene ID
6334
Synonym
MED; Sodium channel protein type VIII subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.6
Sequence
MAARLLAPPGPDSFKPFTPESLANIERRIAESKLKKPPKADGSHREDDEDSKPKPNSDLE
AGKSLPFIYGDIPQGLVAVPLEDFDPYYLTQKTFVVLNRGKTLFRFSATPALYILSPFNL
IRRIAIKILIHSVFSMIIMCTILTNCVFMTFSNPPDWSKNVEYTFTGIYTFESLVKIIAR
GFCIDGFTFLRDPWNWLDFSVIMMAYITEFVNLGNVSALRTFRVLRALKTISVIPGLKTI
VGALIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCVVWPINFNESYLENGTKGF
DWEEYINNKTNFYTVPGMLEPLLCGNSSDAGQCPEGYQCMKAGRNPNYGYTSFDTFSWAF
LALFRLMTQDYWENLYQLTLRAAGKTYMIFFVLVIFVGSFYLVNLILAVVAMAYEEQNQA
TLEEAEQKEAEFKAMLEQLKKQQEEAQAAAMATSAGTVSEDAIEEEGEEGGGSPRSSSEI
SKLSSKSAKERRNRRKKRKQKELSEGEEKGDPEKVFKSESEDGMRRKAFRLPDNRIGRKF
SIMNQSLLSIPGSPFLSRHNSKSSIFSFRGPGRFRDPGSENEFADDEHSTVEESEGRRDS
LFIPIRARERRSSYSGYSGYSQGSRSSRIFPSLRRSVKRNSTVDCNGVVSLIGGPGSHIG
GRLLPEATTEVEIKKKGPGSLLVSMDQLASYGRKDRINSIMSVVTNTLVEELEESQRKCP
PCWYKFANTFLIWECHPYWIKLKEIVNLIVMDPFVDLAITICIVLNTLFMAMEHHPMTPQ
FEHVLAVGNLVFTGIFTAEMFLKLIAMDPYYYFQEGWNIFDGFIVSLSLMELSLADVEGL
SVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGMQLFGKS
YKECVCKINQDCELPRWHMHDFFHSFLIVFRVLCGEWIETMWDCMEVAGQAMCLIVFMMV
MVIGNLVVLNLFLALLLSSFSADNLAATDDDGEMNNLQISVIRIKKGVAWTKLKVHAFMQ
AHFKQREADEVKPLDELYEKKANCIANHTGADIHRNGDFQKNGNGTTSGIGSSVEKYIID
EDHMSFINNPNLTVRVPIAVGESDFENLNTEDVSSESDPEGSKDKLDDTSSSEGSTIDIK
PEVEEVPVEQPEEYLDPDACFTEGCVQRFKCCQVNIEEGLGKSWWILRKTCFLIVEHNWF
ETFIIFMILLSSGALAFEDIYIEQRKTIRTILEYADKVFTYIFILEMLLKWTAYGFVKFF
TNAWCWLDFLIVAVSLVSLIANALGYSELGAIKSLRTLRALRPLRALSRFEGMRVVVNAL
VGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKYHYCFNETSEIRFEIEDVNNKTECEKLM
EGNNTEIRWKNVKINFDNVGAGYLALLQVATFKGWMDIMYAAVDSRKPDEQPKYEDNIYM
YIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNAMKKLGSKKP
QKPIPRPLNKIQGIVFDFVTQQAFDIVIMMLICLNMVTMMVETDTQSKQMENILYWINLV
FVIFFTCECVLKMFALRHYYFTIGWNIFDFVVVILSIVGMFLADIIEKYFVSPTLFRVIR
LARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIFSIFGMSNFAYVKHEA
GIDDMFNFETFGNSMICLFQITTSAGWDGLLLPILNRPPDCSLDKEHPGSGFKGDCGNPS
VGIFFFVSYIIISFLIVVNMYIAIILENFSVATEESADPLSEDDFETFYEIWEKFDPDAT
QFIEYCKLADFADALEHPLRVPKPNTIELIAMDLPMVSGDRIHCLDILFAFTKRVLGDSG
ELDILRQQMEERFVASNPSKVSYEPITTTLRRKQEEVSAVVLQRAYRGHLARRGFICKKT
TSNKLENGGTHREKKESTPSTASLPSYDSVTKPEKEKQQRAEEGRRERAKRQKEVRESKC

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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. [Isoform 5]: In macrophages and melanoma cells, may participate in the control of podosome and invadopodia formation.

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Taxonomy ID
9606
TCDB ID
1.A.1.10.8
        Click to Show/Hide the Complete Species Lineage
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    U1-theraphotoxin-Ap1a Inhibition rate . [1]
 Toxin Info    O- MrVIA IC50
4.67 ± 0.5 mM
 [2]
 Toxin Info    PTx2-18 IC50
>17 nM
 [3]
 Toxin Info    PTx2-19 IC50
>17 nM
 [3]
 Toxin Info    Mu/omega-theraphotoxin-Pmu1a IC50
9.9 nM
 [4]
 Toxin Info    ProTX-11 IC50
75 ± 21 nM
 [3]
 Toxin Info    [R26A]gHwTx-IV IC50
109.3 ± 48.2 nM
 [5]
 Toxin Info    Mu-theraphotoxin-Os1a IC50
115 nM
 [6]
 Toxin Info    Mu-theraphotoxin-Pn3a IC50
129 nM
 [7- 12]
 Toxin Info    PTx2-3258 IC50
382 nM
 [13]
 Toxin Info    PTx2-3127 IC50
608 nM
 [14]
 Toxin Info    PTx2-10 IC50
>17 μM
 [3]
 Toxin Info    PTx2-11 IC50
>17 μM
 [3]
 Toxin Info    PTx2-12 IC50
>17 μM
 [3]
 Toxin Info    PTx2-13 IC50
>17 μM
 [3]
 Toxin Info    PTx2-14 IC50
>17 μM
 [3]
 Toxin Info    PTx2-15 IC50
>17 μM
 [3]
 Toxin Info    PTx2-16 IC50
>17 μM
 [3]
 Toxin Info    PTx2-20 IC50
>17 μM
 [3]
 Toxin Info    PTx2-22 IC50
>17 μM
 [3]
 Toxin Info    PTx2-23 IC50
>17 μM
 [3]
 Toxin Info    PTx2-5 IC50
>17 μM
 [3]
 Toxin Info    PTx2-6 IC50
>17 μM
 [3]
 Toxin Info    PTx2-8 IC50
>17 μM
 [3]
 Toxin Info    PTx2-9 IC50
>17 μM
 [3]
 Toxin Info    PTx2-1 IC50
1.185 ± 0.219 μM
 [3]
 Toxin Info    PTx2-2 IC50
1.234 ± 0.304 μM
 [3]
 Toxin Info    PTx2-17 IC50
2.609 ± 0.756 μM
 [3]
 Toxin Info    PTx2-4 IC50
3.944 ± 0. 127 μM
 [3]
 Toxin Info    PTx2-3 IC50
4.830 ± 1.304 μM
 [3]
 Toxin Info    PTx2-7 IC50
10.330 ± 3.432 μM
 [3]
 Toxin Info    PTx2-21 IC50
11.11 μM
 [3]
 Toxin Info    Toxin Aah4 IC50
15 μM
 [15], [16], [17], [18]
 Toxin Info    Mu-scoloptoxin(03)-Ssm2a IC50
15.2 μM
 [19], [20], [21]
References
Ref 1 Characterization of a novel peptide toxin from Acanthoscurria paulensis spider venom: a distinct cysteine assignment to the HWTX-II family. Biochemistry. 2013 Apr 9;52(14):2440-52. doi: 10.1021/bi4000035. Epub 2013 Mar 29.
Ref 2 Isolation, characterization and total regioselective synthesis of the novel O-conotoxin MfVIA from Conus magnificus that targets voltage-gated sodium channels. Biochem Pharmacol. 2012 Aug 15;84(4):540-8. doi: 10.1016/j.bcp.2012.05.008. Epub 2012 May 16.
Ref 3 Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Na(v)1.7 for the Treatment of Pain. J Med Chem. 2022 Jan 13;65(1):485-496. doi: 10.1021/acs.jmedchem.1c01570. Epub 2021 Dec 21.
Ref 4 Pmu1a, a novel spider toxin with dual inhibitory activity at pain targets hNa(V) 1.7 and hCa(V) 3 voltage-gated channels. FEBS J. 2023 Jul;290(14):3688-3702. doi: 10.1111/febs.16773. Epub 2023 Mar 23.
Ref 5 Manipulation of a spider peptide toxin alters its affinity for lipid bilayers and potency and selectivity for voltage-gated sodium channel subtype 1.7. J Biol Chem. 2020 Apr 10;295(15):5067-5080. doi: 10.1074/jbc.RA119.012281. Epub 2020 Mar 5.
Ref 6 From identification to functional characterization of cyriotoxin-1a, an antinociceptive toxin from the spider Cyriopagopus schioedtei. Br J Pharmacol. 2019 May;176(9):1298-1314. doi: 10.1111/bph.14628. Epub 2019 Apr 9.
Ref 7 Pharmacological characterisation of the highly Na(V)1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 Jan 20;7:40883. doi: 10.1038/srep40883.
Ref 8 Corrigendum: Pharmacological characterisation of the highly Na(V)1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 May 26;7:46816. doi: 10.1038/srep46816.
Ref 9 Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen. Pain. 2019 Aug;160(8):1766-1780. doi: 10.1097/j.pain.0000000000001567.
Ref 10 Chemical Synthesis, Proper Folding, Na(v) Channel Selectivity Profile and Analgesic Properties of the Spider Peptide Phlotoxin 1. Toxins (Basel). 2019 Jun 21;11(6):367. doi: 10.3390/toxins11060367.
Ref 11 Spider Venom Peptide Pn3a Inhibition of Primary Afferent High Voltage-Activated Calcium Channels. Front Pharmacol. 2021 Jan 28;11:633679. doi: 10.3389/fphar.2020.633679. eCollection 2020.
Ref 12 -Theraphotoxin Pn3a inhibition of Ca(V)3.3 channels reveals a novel isoform-selective drug binding site. Elife. 2022 Jul 20;11:e74040. doi: 10.7554/eLife.74040.
Ref 13 The alchemy of culture: intoxicants in society. BMJ. 1998 Nov 28;317(7171):1532B. doi: 10.1136/bmj.317.7171.1532b.
Ref 14 Computational design of peptides to target Na(V)1.7 channel with high potency and selectivity for the treatment of pain. Elife. 2022 Dec 28;11:e81727. doi: 10.7554/eLife.81727.
Ref 15 Evidence for a position-specific deletion as an evolutionary link between long- and short-chain scorpion toxins. FEBS Lett. 2001 Apr 13;494(3):246-8. doi: 10.1016/s0014-5793(01)02336-5.
Ref 16 The amino acid sequence of toxin IV from the Androctonus australis scorpion: differing effects of natural mutations in scorpion alpha-toxins on their antigenic and toxic properties. Nat Toxins. 1992;1(1):61-9. doi: 10.1002/nt.2620010112.
Ref 17 Large scale purification of toxins from the venom of the scorpion Androctonus australis Hector. Toxicon. 1986;24(11-12):1131-9. doi: 10.1016/0041-0101(86)90139-x.
Ref 18 AaHIV a sodium channel scorpion toxin inhibits the proliferation of DU145 prostate cancer cells. Biochem Biophys Res Commun. 2020 Jan 8;521(2):340-346. doi: 10.1016/j.bbrc.2019.10.115. Epub 2019 Oct 24.
Ref 19 Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17534-9. doi: 10.1073/pnas.1306285110. Epub 2013 Sep 30.
Ref 20 Engineering potent and selective analogues of GpTx-1, a tarantula venom peptide antagonist of the Na(V)1.7 sodium channel. J Med Chem. 2015 Mar 12;58(5):2299-314. doi: 10.1021/jm501765v. Epub 2015 Feb 19.
Ref 21 Weaponization of a Hormone: Convergent Recruitment of Hyperglycemic Hormone into the Venom of Arthropod Predators. Structure. 2015 Jul 7;23(7):1283-92. doi: 10.1016/j.str.2015.05.003. Epub 2015 Jun 11.
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