ID   CTXL_HOTTA              Reviewed;          62 AA.
AC   P81761; Q8T0X4;
DT   10-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT   26-SEP-2003, sequence version 2.
DT   03-AUG-2022, entry version 69.
DE   RecName: Full=Lepidopteran-selective toxin;
DE   AltName: Full=BTChl2;
DE   AltName: Full=ButaIT {ECO:0000303|PubMed:16542451};
DE   Flags: Precursor;
OS   Hottentotta tamulus (Eastern Indian scorpion) (Mesobuthus tamulus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX   NCBI_TaxID=34647;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RA   Newton K.A., Armugam A., Strong P.N., Jeyaseelan K.;
RT   "Insect toxin from Mesobuthus tamulus.";
RL   Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 25-61, FUNCTION, SUBCELLULAR LOCATION, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=11782289; DOI=10.1186/1471-2091-2-16;
RA   Wudayagiri R., Inceoglu A.B., Herrmann R., Derbel M., Choudary P.V.,
RA   Hammock B.D.;
RT   "Isolation and characterization of a novel lepidopteran-selective toxin
RT   from the venom of South Indian red scorpion, Mesobuthus tamulus.";
RL   BMC Biochem. 2:16-16(2001).
RN   [3]
RP   BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX   PubMed=16542451; DOI=10.1186/1472-6750-6-18;
RA   Pham Trung N., Fitches E., Gatehouse J.A.;
RT   "A fusion protein containing a lepidopteran-specific toxin from the South
RT   Indian red scorpion (Mesobuthus tamulus) and snowdrop lectin shows oral
RT   toxicity to target insects.";
RL   BMC Biotechnol. 6:18-18(2006).
RN   [4]
RP   BIOTECHNOLOGY, AND RECOMBINANT EXPRESSION AS A CHIMERIC VARIANT.
RX   PubMed=19728320; DOI=10.1002/ps.1833;
RA   Fitches E.C., Bell H.A., Powell M.E., Back E., Sargiotti C., Weaver R.J.,
RA   Gatehouse J.A.;
RT   "Insecticidal activity of scorpion toxin (ButaIT) and snowdrop lectin (GNA)
RT   containing fusion proteins towards pest species of different orders.";
RL   Pest Manag. Sci. 66:74-83(2010).
CC   -!- FUNCTION: Toxin with unknown function in healthy organisms. On glioma
CC       cells, interacts with chloride channels (probably ClC-3/CLCN3) and MMP2
CC       at the surface of glioma cells. This complex is then internalized via
CC       caveolae, thus inhibiting the chloride channels necessary for cell
CC       shrinkage and tumor propagation (By similarity). Induces flaccid
CC       paralysis in H.virescens larvae. Is not toxic to S.falculata larvae or
CC       mice. {ECO:0000250|UniProtKB:Q9UAD0, ECO:0000269|PubMed:11782289}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11782289}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:11782289}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000250|UniProtKB:P15222}.
CC   -!- MASS SPECTROMETRY: Mass=3856.7; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:11782289};
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 ButaIT/GNA
CC       variant shows a gain in toxicity against insects when administered
CC       orally, while maintaining similar effects as the wild-type toxin when
CC       injected (toxic to insects and non-toxic to mammals).
CC       {ECO:0000305|PubMed:16542451}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Chloride
CC       channel inhibitor family. {ECO:0000255|PROSITE-ProRule:PRU00545}.
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DR   EMBL; AF481881; AAL87237.1; -; mRNA.
DR   AlphaFoldDB; P81761; -.
DR   SMR; P81761; -.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0017081; F:chloride channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0019870; F:potassium channel inhibitor activity; NAS:UniProtKB.
DR   GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR   GO; GO:0035821; P:modulation of process of another organism; IDA:UniProtKB.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR007958; Scorpion_toxinS_Cl_inh.
DR   Pfam; PF05294; Toxin_5; 1.
DR   SUPFAM; SSF57095; SSF57095; 1.
DR   PROSITE; PS51200; SHORT_SCORPION_CHLORIDE; 1.
PE   1: Evidence at protein level;
KW   Chloride channel impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Secreted; Signal;
KW   Toxin; Voltage-gated chloride channel impairing toxin.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000269|PubMed:11782289"
FT   CHAIN           25..61
FT                   /note="Lepidopteran-selective toxin"
FT                   /id="PRO_0000035331"
FT   PROPEP          62
FT                   /evidence="ECO:0000305"
FT                   /id="PRO_0000035332"
FT   DISULFID        26..43
FT                   /evidence="ECO:0000250|UniProtKB:P15222,
FT                   ECO:0000255|PROSITE-ProRule:PRU00545"
FT   DISULFID        29..51
FT                   /evidence="ECO:0000250|UniProtKB:P15222,
FT                   ECO:0000255|PROSITE-ProRule:PRU00545"
FT   DISULFID        40..56
FT                   /evidence="ECO:0000250|UniProtKB:P15222,
FT                   ECO:0000255|PROSITE-ProRule:PRU00545"
FT   DISULFID        44..58
FT                   /evidence="ECO:0000250|UniProtKB:P15222,
FT                   ECO:0000255|PROSITE-ProRule:PRU00545"
SQ   SEQUENCE   62 AA;  6656 MW;  32E0B3AF2382597E CRC64;
     MKFLYGVILI ALFLTVMTAT LSEARCGPCF TTDPQTQAKC SECCGRKGGV CKGPQCICGI
     QY