ID   SCXT2_MESMA             Reviewed;          32 AA.
AC   P0DV30;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   23-FEB-2022, sequence version 1.
DT   03-AUG-2022, entry version 3.
DE   RecName: Full=Sodium channel neurotoxin BmK NT2 {ECO:0000303|PubMed:28591591};
DE   AltName: Full=Alpha-scorpion toxin {ECO:0000303|PubMed:28591591};
DE   Flags: Fragment;
OS   Mesobuthus martensii (Manchurian scorpion) (Buthus martensii).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX   NCBI_TaxID=34649;
RN   [1]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND MASS SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=28591591; DOI=10.1016/j.ijbiomac.2017.05.163;
RA   Zou X., Wu Y., Chen J., Zhao F., Zhang F., Yu B., Cao Z.;
RT   "Activation of sodium channel by a novel alpha-scorpion toxin, BmK NT2,
RT   stimulates ERK1/2 and CERB phosphorylation through a Ca2+ dependent pathway
RT   in neocortical neurons.";
RL   Int. J. Biol. Macromol. 104:70-77(2017).
CC   -!- FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium
CC       channels (Nav) and inhibit the inactivation of the activated channels,
CC       thereby blocking neuronal transmission. This toxin dose-dependently
CC       delays inactivation of voltage-gated sodium channels (Nav) (EC(50)=0.91
CC       uM), and shifts the steady-state activation and inactivation to
CC       hyperpolarized direction. In addition, it dose-dependently alters
CC       calcium dynamics and increases phosphorylation of MAP kinases 1/3
CC       (MAPK1/MAPK3) and cAMP-response element binding (CREB) proteins in
CC       neocortical neurons. This effect is eliminated by tetrodotoxin, a Nav
CC       blocker. {ECO:0000269|PubMed:28591591}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28591591}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:28591591}.
CC   -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC       antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC       {ECO:0000305}.
CC   -!- MASS SPECTROMETRY: Mass=7010.3; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:28591591};
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
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DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.30.10; -; 1.
DR   InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR002061; Scorpion_toxinL/defensin.
DR   Pfam; PF00537; Toxin_3; 1.
DR   SUPFAM; SSF57095; SSF57095; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Secreted; Toxin; Voltage-gated sodium channel impairing toxin.
FT   CHAIN           1..>32
FT                   /note="Sodium channel neurotoxin BmK NT2"
FT                   /evidence="ECO:0000305|PubMed:28591591"
FT                   /id="PRO_0000454750"
FT   DOMAIN          2..>32
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000305"
FT   DISULFID        12..?
FT                   /evidence="ECO:0000305"
FT   DISULFID        16..?
FT                   /evidence="ECO:0000305"
FT   DISULFID        22..?
FT                   /evidence="ECO:0000305"
FT   DISULFID        26..?
FT                   /evidence="ECO:0000305"
FT   DISULFID        28..?
FT                   /evidence="ECO:0000305"
FT   NON_TER         32
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   32 AA;  3405 MW;  C2278DB1BD9C71AF CRC64;
     VRDAYIAKPE NCVYHCAGNE GCNNLCTCNG AT