ID   SCXN2_MESEU             Reviewed;          85 AA.
AC   P86403; D8UWD7; F1JYX0;
DT   30-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT   03-JUL-2019, sequence version 2.
DT   03-AUG-2022, entry version 28.
DE   RecName: Full=Sodium channel neurotoxin MeuNaTxalpha-2 {ECO:0000303|PubMed:21969612};
DE   Flags: Precursor;
OS   Mesobuthus eupeus (Lesser Asian scorpion) (Buthus eupeus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX   NCBI_TaxID=34648;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 20-29,
RP   FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND AMIDATION AT ARG-83.
RC   TISSUE=Venom, and Venom gland;
RX   PubMed=21969612; DOI=10.1074/mcp.m111.012054;
RA   Zhu S., Peigneur S., Gao B., Lu X., Cao C., Tytgat J.;
RT   "Evolutionary diversification of Mesobuthus alpha-scorpion toxins affecting
RT   sodium channels.";
RL   Mol. Cell. Proteomics 11:M111.012054-M111.012054(2012).
RN   [2]
RP   PROTEIN SEQUENCE OF 20-83, FUNCTION, SUBCELLULAR LOCATION, MASS
RP   SPECTROMETRY, AND AMIDATION AT ARG-83.
RC   TISSUE=Venom;
RA   Zhu S.Y., Gao B.;
RT   "Characterization of a sodium channel toxin from the scorpion Mesobuthus
RT   eupeus venom.";
RL   Submitted (NOV-2009) to UniProtKB.
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 inhibits
CC       inactivation of Nav1.4/SCN4A (EC(50)=2.23 uM) and drosophila DmNav1
CC       (EC(50)=220 nM) (PubMed:21969612, Ref.2). The toxin (1 uM) does not
CC       significantly shift the midpoint of activation at the two channels, but
CC       induces a significant depolarizing shift in the V(1/2) of inactivation
CC       of the channels (PubMed:21969612). In addition, the toxin accelerates
CC       the recovery from fast inactivation in Nav1.4/SCN4A and DmNav1
CC       (PubMed:21969612). It also shows antimicrobial activity (Ref.2).
CC       {ECO:0000269|PubMed:21969612, ECO:0000269|Ref.2}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21969612}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:21969612}.
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=7233.68; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:21969612, ECO:0000269|Ref.2};
CC   -!- MISCELLANEOUS: Shows no effect on Nav1.2/SCN2A, Nav1.3/SCN3A,
CC       Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A and Nav1.8/SCN10A
CC       (PubMed:21969612). {ECO:0000269|PubMed:21969612}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Alpha subfamily. {ECO:0000255}.
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DR   EMBL; HQ332135; ADW41700.1; -; Genomic_DNA.
DR   EMBL; JF304616; ADY16679.1; -; mRNA.
DR   EMBL; GQ249202; ADF49574.1; -; mRNA.
DR   AlphaFoldDB; P86403; -.
DR   SMR; P86403; -.
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   GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR   CDD; cd00107; Knot1; 1.
DR   Gene3D; 3.30.30.10; -; 1.
DR   InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR   InterPro; IPR003614; Scorpion_toxin-like.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR018218; Scorpion_toxinL.
DR   InterPro; IPR002061; Scorpion_toxinL/defensin.
DR   Pfam; PF00537; Toxin_3; 1.
DR   PRINTS; PR00285; SCORPNTOXIN.
DR   SMART; SM00505; Knot1; 1.
DR   SUPFAM; SSF57095; SSF57095; 1.
DR   PROSITE; PS51863; LCN_CSAB; 1.
PE   1: Evidence at protein level;
KW   Amidation; Antibiotic; Antimicrobial; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin; Secreted; Signal;
KW   Toxin; Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:21969612, ECO:0000269|Ref.2"
FT   CHAIN           20..83
FT                   /note="Sodium channel neurotoxin MeuNaTxalpha-2"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="PRO_0000401120"
FT   DOMAIN          21..83
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   MOD_RES         83
FT                   /note="Arginine amide"
FT                   /evidence="ECO:0000269|PubMed:21969612, ECO:0000269|Ref.2"
FT   DISULFID        31..82
FT                   /evidence="ECO:0000250|UniProtKB:P86405"
FT   DISULFID        35..55
FT                   /evidence="ECO:0000250|UniProtKB:P86405"
FT   DISULFID        41..65
FT                   /evidence="ECO:0000250|UniProtKB:P86405"
FT   DISULFID        45..67
FT                   /evidence="ECO:0000250|UniProtKB:P86405"
SQ   SEQUENCE   85 AA;  9536 MW;  5CDA66CFB31E7110 CRC64;
     MNYLVMISLA LLLMTGVESA RDAYIANDRN CVYTCALNPY CDSECKKNGA DSGYCQWFGR
     FGNACWCKNL PDKVPIRIPG ECRGR