Target Information

General Information of This Target
Target ID
BTDT00179
Target Name
Sodium channel protein type 2 subunit alpha (SCN2A)
Target Bioclass
Transporter and channel
Uniprot ID
Q99250
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
SCN2A
Gene ID
6326
Synonym
HBSC II; Sodium channel protein brain II subunit alpha; Sodium channel protein type II subunit alpha; Voltage-gated sodium channel subunit alpha Nav1.2
Sequence
MAQSVLVPPGPDSFRFFTRESLAAIEQRIAEEKAKRPKQERKDEDDENGPKPNSDLEAGK
SLPFIYGDIPPEMVSVPLEDLDPYYINKKTFIVLNKGKAISRFSATPALYILTPFNPIRK
LAIKILVHSLFNMLIMCTILTNCVFMTMSNPPDWTKNVEYTFTGIYTFESLIKILARGFC
LEDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGA
LIQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCLQWPPDNSSFEINITSFFNNSL
DGNGTTFNRTVSIFNWDEYIEDKSHFYFLEGQNDALLCGNSSDAGQCPEGYICVKAGRNP
NYGYTSFDTFSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLI
LAVVAMAYEEQNQATLEEAEQKEAEFQQMLEQLKKQQEEAQAAAAAASAESRDFSGAGGI
GVFSESSSVASKLSSKSEKELKNRRKKKKQKEQSGEEEKNDRVRKSESEDSIRRKGFRFS
LEGSRLTYEKRFSSPHQSLLSIRGSLFSPRRNSRASLFSFRGRAKDIGSENDFADDEHST
FEDNDSRRDSLFVPHRHGERRHSNVSQASRASRVLPILPMNGKMHSAVDCNGVVSLVGGP
STLTSAGQLLPEGTTTETEIRKRRSSSYHVSMDLLEDPTSRQRAMSIASILTNTMEELEE
SRQKCPPCWYKFANMCLIWDCCKPWLKVKHLVNLVVMDPFVDLAITICIVLNTLFMAMEH
YPMTEQFSSVLSVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIVSLSLMELGL
ANVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAIIVFIFAVVGM
QLFGKSYKECVCKISNDCELPRWHMHDFFHSFLIVFRVLCGEWIETMWDCMEVAGQTMCL
TVFMMVMVIGNLVVLNLFLALLLSSFSSDNLAATDDDNEMNNLQIAVGRMQKGIDFVKRK
IREFIQKAFVRKQKALDEIKPLEDLNNKKDSCISNHTTIEIGKDLNYLKDGNGTTSGIGS
SVEKYVVDESDYMSFINNPSLTVTVPIAVGESDFENLNTEEFSSESDMEESKEKLNATSS
SEGSTVDIGAPAEGEQPEVEPEESLEPEACFTEDCVRKFKCCQISIEEGKGKLWWNLRKT
CYKIVEHNWFETFIVFMILLSSGALAFEDIYIEQRKTIKTMLEYADKVFTYIFILEMLLK
WVAYGFQVYFTNAWCWLDFLIVDVSLVSLTANALGYSELGAIKSLRTLRALRPLRALSRF
EGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCINYTTGEMFDVSVV
NNYSECKALIESNQTARWKNVKVNFDNVGLGYLSLLQVATFKGWMDIMYAAVDSRNVELQ
PKYEDNLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFMTEEQKKYYNA
MKKLGSKKPQKPIPRPANKFQGMVFDFVTKQVFDISIMILICLNMVTMMVETDDQSQEMT
NILYWINLVFIVLFTGECVLKLISLRYYYFTIGWNIFDFVVVILSIVGMFLAELIEKYFV
SPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYAIFGMS
NFAYVKREVGIDDMFNFETFGNSMICLFQITTSAGWDGLLAPILNSGPPDCDPDKDHPGS
SVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPLSEDDFEMFYE
VWEKFDPDATQFIEFAKLSDFADALDPPLLIAKPNKVQLIAMDLPMVSGDRIHCLDILFA
FTKRVLGESGEMDALRIQMEERFMASNPSKVSYEPITTTLKRKQEEVSAIIIQRAYRRYL
LKQKVKKVSSIYKKDKGKECDGTPIKEDTLIDKLNENSTPEKTDMTPSTTSPPSYDSVTK
PEKEKFEKDKSEKEDKGKDIRESKK

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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. Implicated in the regulation of hippocampal replay occurring within sharp wave ripples (SPW-R) important for memory.

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Taxonomy ID
9606
TCDB ID
1.A.1.10.12
        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    Mu-theraphotoxin-Phlo1a Inhibition rate
<20 %
 [2]
 Toxin Info    Mu-theraphotoxin-Phlo1b Inhibition rate
37 %
 [2]
 Toxin Info    O- MrVIA IC50
6.3 ± 0.7 mM
 [3]
 Toxin Info    [R26A]gHwTx-IV IC50
22.4 ± 1.2 nM
 [4]
 Toxin Info    Mu-theraphotoxin-Os1a IC50
75.5 nM
 [5]
 Toxin Info    Mu-theraphotoxin-Pn3a IC50
124 nM
 [6- 11]
 Toxin Info    Mu-theraphotoxin-Phlo2a IC50
404 nM
 [2]
 Toxin Info    Mu-scoloptoxin(03)-Ssm2a IC50
813 nM
 [12], [13], [14]
 Toxin Info    Beta-theraphotoxin-Cd1a IC50
0.13 μM
 [15]
 Toxin Info    PTx2-3258 IC50
3.399 μM
 [16]
 Toxin Info    PTx2-3127 IC50
5.04 μM
 [17]
 Toxin Info    rHwTx-IV (W30Y) pIC50
>4.3 .
 [18]
 Toxin Info    rHwTx-IV (R26G) pIC50
>5.4 .
 [18]
 Toxin Info    rHwTx-IV (W30K) pIC50
>5.5 .
 [18]
 Toxin Info    rHwTx-IV (K18F) pIC50
5.0 ± 2.6 .
 [18]
 Toxin Info    rHwTx-IV (G36I) pIC50
5.4 ± 0.5 .
 [18]
 Toxin Info    rHwTx-IV (D14P) pIC50
5.5 ± 0.51 .
 [18]
 Toxin Info    rHwTx-IV (R26K) pIC50
5.8 ± 0.13 .
 [18]
 Toxin Info    rHwTx-IV (K27W) pIC50
5.8 ± 0.31 .
 [18]
 Toxin Info    rHwTx-IV (N13G) pIC50
5.8 ± 0.43 .
 [18]
 Toxin Info    rHwTx-IV (Y33T) pIC50
6.2 ± 0.05 .
 [18]
 Toxin Info    rHwTx-IV (S19Q) pIC50
6.4 ± 1.1 .
 [18]
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 Three Peptide Modulators of the Human Voltage-Gated Sodium Channel 1.7, an Important Analgesic Target, from the Venom of an Australian Tarantula. Toxins (Basel). 2015 Jun 30;7(7):2494-513. doi: 10.3390/toxins7072494.
Ref 3 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 4 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 5 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 6 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 7 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 8 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 9 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 10 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 11 -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 12 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 13 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 14 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.
Ref 15 Discovery and mode of action of a novel analgesic -toxin from the African spider Ceratogyrus darlingi. PLoS One. 2017 Sep 7;12(9):e0182848. doi: 10.1371/journal.pone.0182848. eCollection 2017.
Ref 16 The alchemy of culture: intoxicants in society. BMJ. 1998 Nov 28;317(7171):1532B. doi: 10.1136/bmj.317.7171.1532b.
Ref 17 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 18 Comprehensive engineering of the tarantula venom peptide huwentoxin-IV to inhibit the human voltage-gated sodium channel hNa(v)1.7. J Biol Chem. 2020 Jan 31;295(5):1315-1327. doi: 10.1074/jbc.RA119.011318. Epub 2019 Dec 23.
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