ID   SCX3_ANDAU              Reviewed;          84 AA.
AC   P01480;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 3.
DT   25-MAY-2022, entry version 112.
DE   RecName: Full=Alpha-mammal toxin Aah3;
DE   AltName: Full=AaH III {ECO:0000303|PubMed:2808423};
DE            Short=AaHIII;
DE   AltName: Full=Neurotoxin 3;
DE   AltName: Full=Neurotoxin III;
DE   Flags: Precursor;
OS   Androctonus australis (Sahara scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Androctonus.
OX   NCBI_TaxID=6858;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Hector;
RX   PubMed=2808423; DOI=10.1016/s0021-9258(19)47295-5;
RA   Bougis P.E., Rochat H., Smith L.A.;
RT   "Precursors of Androctonus australis scorpion neurotoxins. Structures of
RT   precursors, processing outcomes, and expression of a functional recombinant
RT   toxin II.";
RL   J. Biol. Chem. 264:19259-19265(1989).
RN   [2]
RP   PROTEIN SEQUENCE OF 20-83.
RC   STRAIN=Hector; TISSUE=Venom;
RX   PubMed=428402; DOI=10.1111/j.1432-1033.1979.tb12931.x;
RA   Kopeyan C., Martinez G., Rochat H.;
RT   "Amino acid sequence of neurotoxin III of the scorpion Androctonus
RT   austrialis Hector.";
RL   Eur. J. Biochem. 94:609-615(1979).
RN   [3]
RP   TOXIC DOSE.
RX   PubMed=1846301; DOI=10.1021/bi00217a007;
RA   Loret E.P., Martin-Eauclaire M.-F., Mansuelle P., Sampieri F., Granier C.,
RA   Rochat H.;
RT   "An anti-insect toxin purified from the scorpion Androctonus australis
RT   hector also acts on the alpha- and beta-sites of the mammalian sodium
RT   channel: sequence and circular dichroism study.";
RL   Biochemistry 30:633-640(1991).
RN   [4]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RC   STRAIN=Hector;
RX   PubMed=2279844; DOI=10.1111/j.1399-3011.1990.tb00971.x;
RA   Laplante S.R., Mikou A., Robin M., Guittet E., Delsuc M.-A.,
RA   Charpentier I., Lallemand J.-Y.;
RT   "Rapid determination and NMR assignments of antiparallel sheets and helices
RT   of a scorpion and a cobra toxin.";
RL   Int. J. Pept. Protein Res. 36:227-230(1990).
RN   [5]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RC   STRAIN=Hector;
RX   PubMed=1422146; DOI=10.1007/bf02192800;
RA   Mikou A., Laplante S.R., Guittet E., Lallemand J.-Y.,
RA   Martin-Eauclaire M.-F., Rochat H.;
RT   "Toxin III of the scorpion Androctonus australis hector: proton nuclear
RT   magnetic resonance assignments and secondary structure.";
RL   J. Biomol. NMR 2:57-70(1992).
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.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
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   -!- TOXIC DOSE: LD(50) is 0.35 pg/kg by intracerebroventricular injection
CC       into mice. {ECO:0000269|PubMed:1846301}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M27703; AAA29948.1; -; mRNA.
DR   PIR; C34444; NTSR3A.
DR   AlphaFoldDB; P01480; -.
DR   BMRB; P01480; -.
DR   SMR; P01480; -.
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   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; IPR002061; Scorpion_toxinL/defensin.
DR   Pfam; PF00537; Toxin_3; 1.
DR   SMART; SM00505; Knot1; 1.
DR   SUPFAM; SSF57095; SSF57095; 1.
DR   PROSITE; PS51863; LCN_CSAB; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated sodium channel impairing toxin.
FT   SIGNAL          1..19
FT                   /evidence="ECO:0000269|PubMed:428402"
FT   CHAIN           20..83
FT                   /note="Alpha-mammal toxin Aah3"
FT                   /id="PRO_0000035221"
FT   PROPEP          84
FT                   /note="Removed by a carboxypeptidase"
FT                   /id="PRO_0000035222"
FT   DOMAIN          21..82
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        31..81
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        35..53
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        39..63
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        43..65
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   CONFLICT        27
FT                   /note="D -> N (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   84 AA;  9068 MW;  ADB0AD462153E3C0 CRC64;
     MNYLVMISLA LLLMTGVESV RDGYIVDSKN CVYHCVPPCD GLCKKNGAKS GSCGFLIPSG
     LACWCVALPD NVPIKDPSYK CHSR