ID   SCX3_BUTOC              Reviewed;          72 AA.
AC   P01485;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 2.
DT   03-AUG-2022, entry version 99.
DE   RecName: Full=Alpha-mammal toxin Bot3;
DE   AltName: Full=Bot III;
DE            Short=BotIII;
DE   AltName: Full=Neurotoxin III;
DE   Flags: Precursor; Fragment;
OS   Buthus occitanus tunetanus (Common European scorpion) (Buthus tunetanus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Buthus.
OX   NCBI_TaxID=6871;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-66, AMIDATION AT ASN-72, FUNCTION,
RP   AND MUTAGENESIS OF ASN-72.
RC   TISSUE=Muscle;
RX   PubMed=15062995; DOI=10.1016/j.peptides.2004.01.009;
RA   Benkhadir K., Kharrat R., Cestele S., Mosbah A., Rochat H., el Ayeb M.,
RA   Karoui H.;
RT   "Molecular cloning and functional expression of the alpha-scorpion toxin
RT   BotIII: pivotal role of the C-terminal region for its interaction with
RT   voltage-dependent sodium channels.";
RL   Peptides 25:151-161(2004).
RN   [2]
RP   PROTEIN SEQUENCE OF 9-72, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RA   Vargas O., Gregoire J., Martin M.-F., Bechis G., Rochat H.;
RT   "Neurotoxins from the venoms of two scorpions: Buthus occitanus tunetanus
RT   and Buthus occitanus mardochei.";
RL   Toxicon 20:79-79(1982).
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. Is active against mammals and
CC       binds with high affinity to rat brain synaptosomes.
CC       {ECO:0000269|PubMed:15062995}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.2}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.2}.
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   -!- PTM: When the toxin is not amidated, there are 75% loss of toxicity to
CC       mice, and total incapacity to bind rat brain synaptosomes.
CC       {ECO:0000269|PubMed:15062995}.
CC   -!- TOXIC DOSE: LD(50) is 1.25 ug/kg (25 ng/mouse) by
CC       intracerebroventricular injection into mice.
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   PIR; A01745; NTSR3B.
DR   AlphaFoldDB; P01485; -.
DR   SMR; P01485; -.
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:0006952; P:defense response; IEA:InterPro.
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; Direct protein sequencing; Disulfide bond;
KW   Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          <1..8
FT                   /evidence="ECO:0000269|Ref.2"
FT   CHAIN           9..72
FT                   /note="Alpha-mammal toxin Bot3"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="PRO_0000066734"
FT   DOMAIN          10..72
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   MOD_RES         72
FT                   /note="Asparagine amide"
FT                   /evidence="ECO:0000269|PubMed:15062995"
FT   DISULFID        20..71
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        24..44
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        30..54
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        34..56
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   MUTAGEN         72
FT                   /note="N->H: No change in lethal activity to mice; when N-
FT                   72 is not amidated."
FT                   /evidence="ECO:0000269|PubMed:15062995"
FT   MUTAGEN         72
FT                   /note="N->NGR: Total loss of lethal activity, and
FT                   incapacity to bind rat brain synaptosomes."
FT                   /evidence="ECO:0000269|PubMed:15062995"
FT   NON_TER         1
SQ   SEQUENCE   72 AA;  8059 MW;  CA67CCCBBEB9BA6B CRC64;
     LVMAGVESVK DGYIVDDRNC TYFCGRNAYC NEECTKLKGE SGYCQWASPY GNACYCYKVP
     DHVRTKGPGR CN