ID   SIX1_ANDAU              Reviewed;          88 AA.
AC   P01497;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 2.
DT   24-JAN-2024, entry version 114.
DE   RecName: Full=Beta-insect excitatory toxin 1 {ECO:0000305};
DE   AltName: Full=AaH IT1 {ECO:0000303|PubMed:2808423};
DE            Short=AaH IT {ECO:0000303|PubMed:2808423};
DE            Short=AaHIT;
DE            Short=AaHIT1;
DE            Short=AaIT {ECO:0000303|PubMed:25641865};
DE            Short=AaIT1;
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; TISSUE=Venom gland;
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 19-88, FUNCTION, BIOASSAY, TOXIC DOSE, AND SUBCELLULAR
RP   LOCATION.
RC   STRAIN=Hector; TISSUE=Venom;
RX   PubMed=2334710; DOI=10.1021/bi00458a021;
RA   Loret E.P., Mansuelle P., Rochat H., Granier C.;
RT   "Neurotoxins active on insects: amino acid sequences, chemical
RT   modifications, and secondary structure estimation by circular dichroism of
RT   toxins from the scorpion Androctonus australis hector.";
RL   Biochemistry 29:1492-1501(1990).
RN   [3]
RP   PROTEIN SEQUENCE OF 19-88, SUBCELLULAR LOCATION, AND DISULFIDE BONDS.
RX   PubMed=7174197; DOI=10.1111/j.1399-3011.1982.tb00897.x;
RA   Darbon H., Zlotkin E., Kopeyan C., van Rietschoten J., Rochat H.;
RT   "Covalent structure of the insect toxin of the North African scorpion
RT   Androctonus australis Hector.";
RL   Int. J. Pept. Protein Res. 20:320-330(1982).
RN   [4]
RP   BIOTECHNOLOGY, AND REVIEW.
RX   PubMed=11086217; DOI=10.1016/s0300-9084(00)01177-9;
RA   Zlotkin E., Fishman Y., Elazar M.;
RT   "AaIT: from neurotoxin to insecticide.";
RL   Biochimie 82:869-881(2000).
RN   [5]
RP   BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT IN
RP   TRANSGENIC PLANTS.
RX   PubMed=25641865; DOI=10.1111/1744-7917.12203;
RA   Liu S.M., Li J., Zhu J.Q., Wang X.W., Wang C.S., Liu S.S., Chen X.X.,
RA   Li S.;
RT   "Transgenic plants expressing the AaIT/GNA fusion protein show increased
RT   resistance and toxicity to both chewing and sucking pests.";
RL   Insect Sci. 23:265-276(2016).
RN   [6]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RC   STRAIN=Hector;
RX   PubMed=1993198; DOI=10.1021/bi00221a016;
RA   Darbon H., Weber C., Braun W.;
RT   "Two-dimensional 1H nuclear magnetic resonance study of AaH IT, an anti-
RT   insect toxin from the scorpion Androctonus australis hector. Sequential
RT   resonance assignments and folding of the polypeptide chain.";
RL   Biochemistry 30:1836-1845(1991).
CC   -!- FUNCTION: Excitatory insect beta-toxins induce a spastic paralysis.
CC       They bind voltage-independently at site-4 of sodium channels (Nav) and
CC       shift the voltage of activation toward more negative potentials thereby
CC       affecting sodium channel activation and promoting spontaneous and
CC       repetitive firing. This toxin is active only on insects
CC       (PubMed:2334710). {ECO:0000269|PubMed:2334710}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2334710,
CC       ECO:0000269|PubMed:7174197}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:2334710, ECO:0000305|PubMed:7174197}.
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: PD(50) is 0.099 ng/mg of insects.
CC       {ECO:0000269|PubMed:2334710}.
CC   -!- BIOTECHNOLOGY: Could be used to reinforce the natural insecticidal
CC       ability of baculoviruses. The insertion of the gene coding for AaHIT
CC       causes a higher killing speed of insects by the baculovirus
CC       (particularly against lepidopterans). {ECO:0000269|PubMed:11086217}.
CC   -!- BIOTECHNOLOGY: Could be considered as a biological insecticide
CC       candidate, when fused to Galanthus nivalis agglutinin (GNA), a protein
CC       with the potential to cross the insect gut. This chimeric AaIT/GNA
CC       variant shows increased resistance and toxicity to both chewing and
CC       sucking pests (the cotton bollworm Helicoverpa armigera, the whitefly
CC       Bemisia tabaci, and the rice brown planthopper Nilaparvata lugens),
CC       when expressed in transgenic plants. {ECO:0000269|PubMed:25641865}.
CC   -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC       Sodium channel inhibitor family. Beta subfamily. {ECO:0000305}.
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DR   EMBL; M27706; AAA29951.1; -; mRNA.
DR   EMBL; M27705; AAA29950.1; -; mRNA.
DR   AlphaFoldDB; P01497; -.
DR   BMRB; P01497; -.
DR   SMR; P01497; -.
DR   ABCD; P01497; 12 sequenced antibodies.
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; Knottin, scorpion toxin-like; 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; Scorpion toxin-like; 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..18
FT                   /evidence="ECO:0000305|PubMed:2334710,
FT                   ECO:0000305|PubMed:7174197"
FT   CHAIN           19..88
FT                   /note="Beta-insect excitatory toxin 1"
FT                   /evidence="ECO:0000269|PubMed:2334710,
FT                   ECO:0000269|PubMed:7174197"
FT                   /id="PRO_0000035187"
FT   DOMAIN          20..83
FT                   /note="LCN-type CS-alpha/beta"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT   DISULFID        34..55
FT                   /evidence="ECO:0000269|PubMed:1993198"
FT   DISULFID        40..60
FT                   /evidence="ECO:0000269|PubMed:1993198"
FT   DISULFID        44..62
FT                   /evidence="ECO:0000269|PubMed:1993198"
FT   DISULFID        56..82
FT                   /evidence="ECO:0000269|PubMed:1993198"
FT   VARIANT         17
FT                   /note="F -> L"
FT   CONFLICT        43
FT                   /note="E -> Q (in Ref. 3; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   88 AA;  9852 MW;  E6FF097B3277748F CRC64;
     MKFLLLFLVV LPIMGVFGKK NGYAVDSSGK APECLLSNYC NNECTKVHYA DKGYCCLLSC
     YCFGLNDDKK VLEISDTRKS YCDTTIIN
//