ID   CTXI1_MESEU             Reviewed;          36 AA.
AC   P15220;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1990, sequence version 1.
DT   03-AUG-2022, entry version 77.
DE   RecName: Full=Insectotoxin-I1 {ECO:0000303|Ref.1};
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   PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RA   Adamovich T.B., Nasimov I.V., Grishin E.V., Ovchinnikov Y.A.;
RT   "Amino acid sequence of insectotoxin I1 from the venom of middle-asian
RT   scorpion Buthus epeus.";
RL   Bioorg. Khim. 3:485-493(1977).
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS), SYNTHESIS, FUNCTION, AND DISULFIDE
RP   BONDS.
RX   PubMed=29483648; DOI=10.1038/s41594-018-0033-9;
RA   Correnti C.E., Gewe M.M., Mehlin C., Bandaranayake A.D., Johnsen W.A.,
RA   Rupert P.B., Brusniak M.Y., Clarke M., Burke S.E., De Van Der Schueren W.,
RA   Pilat K., Turnbaugh S.M., May D., Watson A., Chan M.K., Bahl C.D.,
RA   Olson J.M., Strong R.K.;
RT   "Screening, large-scale production and structure-based classification of
RT   cystine-dense peptides.";
RL   Nat. Struct. Mol. Biol. 25:270-278(2018).
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). Has been shown to
CC       weakly inhibit TRPV1 channels (PubMed:29483648).
CC       {ECO:0000250|UniProtKB:Q9UAD0, ECO:0000269|PubMed:29483648}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.1}.
CC   -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC       structurally defines this protein as a knottin.
CC       {ECO:0000269|PubMed:29483648}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Chloride
CC       channel inhibitor family. {ECO:0000255|PROSITE-ProRule:PRU00545}.
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DR   PIR; JN0402; JN0402.
DR   PDB; 6AVA; X-ray; 2.20 A; A/B=1-36.
DR   PDBsum; 6AVA; -.
DR   AlphaFoldDB; P15220; -.
DR   SMR; P15220; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0017081; F:chloride channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
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   3D-structure; Chloride channel impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Knottin; Secreted; Toxin;
KW   Voltage-gated chloride channel impairing toxin.
FT   PEPTIDE         1..36
FT                   /note="Insectotoxin-I1"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000044935"
FT   DISULFID        2..19
FT                   /evidence="ECO:0000269|PubMed:29483648,
FT                   ECO:0000312|PDB:6AVA"
FT   DISULFID        5..26
FT                   /evidence="ECO:0000269|PubMed:29483648,
FT                   ECO:0000312|PDB:6AVA"
FT   DISULFID        16..31
FT                   /evidence="ECO:0000269|PubMed:29483648,
FT                   ECO:0000312|PDB:6AVA"
FT   DISULFID        20..33
FT                   /evidence="ECO:0000269|PubMed:29483648,
FT                   ECO:0000312|PDB:6AVA"
FT   STRAND          2..4
FT                   /evidence="ECO:0007829|PDB:6AVA"
FT   HELIX           12..19
FT                   /evidence="ECO:0007829|PDB:6AVA"
FT   TURN            20..22
FT                   /evidence="ECO:0007829|PDB:6AVA"
FT   STRAND          24..27
FT                   /evidence="ECO:0007829|PDB:6AVA"
FT   STRAND          30..33
FT                   /evidence="ECO:0007829|PDB:6AVA"
SQ   SEQUENCE   36 AA;  4011 MW;  C75228525076C284 CRC64;
     MCMPCFTTRP DMAQQCRACC KGRGKCFGPQ CLCGYD