ID   CTX5A_MESEU             Reviewed;          35 AA.
AC   P15222;
DT   01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1994, sequence version 2.
DT   03-AUG-2022, entry version 91.
DE   RecName: Full=Insectotoxin-I5A {ECO:0000303|Ref.1};
DE            Short=BeIT5A {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, AMIDATION AT ARG-35, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RA   Grishin E.V., Volkova T.M., Soldatova L.N.;
RT   "Study of toxic components from the venom of caucasus subspecies of
RT   scorpion Buthus eupeus.";
RL   Bioorg. Khim. 8:155-164(1982).
RN   [2]
RP   SEQUENCE REVISION TO 14 AND 23-24, STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=6679783;
RA   Arseniev A.S., Kondakov V.I., Maiorov V.N., Volkova T.M., Grishin E.V.;
RT   "Secondary structure and assignment of signals in two-dimensional 1H-NMR
RT   spectra of the Buthus eupeus neurotoxin I5A.";
RL   Bioorg. Khim. 9:768-793(1983).
RN   [3]
RP   FUNCTION, AND SYNTHESIS.
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).
RN   [4]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=6679765;
RA   Arseniev A.S., Kondakov V.I., Maiorov V.N., Bystrov V.F., Ovchinnikov Y.A.;
RT   "Conformation NMR analysis of the spatial structure of Buthus eupeus
RT   insectotoxin I5A.";
RL   Bioorg. Khim. 9:1667-1689(1983).
RN   [5]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RA   Arseniev A.S., Kondakov V.I., Maiorov V.N., Bystrov V.F.;
RT   "NMR solution spatial structure of 'short' insectotoxin I5A.";
RL   FEBS Lett. 165:57-61(1984).
RN   [6]
RP   STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX   PubMed=1815511;
RA   Lomize A.L., Maiorov V.N., Arseniev A.S.;
RT   "Determination of the spatial structure of insectotoxin I5A from Buthus
RT   erpeus by (1)H-NMR spectroscopy data.";
RL   Bioorg. Khim. 17:1613-1632(1991).
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:6679765, ECO:0000269|Ref.5, ECO:0000312|PDB:1SIS}.
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; JN0361; JN0361.
DR   PDB; 1SIS; NMR; -; A=1-35.
DR   PDBsum; 1SIS; -.
DR   AlphaFoldDB; P15222; -.
DR   SMR; P15222; -.
DR   EvolutionaryTrace; P15222; -.
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; Amidation; Chloride channel impairing toxin;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Knottin; Secreted; Toxin; Voltage-gated chloride channel impairing toxin.
FT   PEPTIDE         1..35
FT                   /note="Insectotoxin-I5A"
FT                   /evidence="ECO:0000269|Ref.1"
FT                   /id="PRO_0000044939"
FT   MOD_RES         35
FT                   /note="Arginine amide"
FT                   /evidence="ECO:0000269|Ref.1"
FT   DISULFID        2..19
FT                   /evidence="ECO:0000269|PubMed:6679765, ECO:0000269|Ref.5,
FT                   ECO:0000312|PDB:1SIS"
FT   DISULFID        5..26
FT                   /evidence="ECO:0000269|PubMed:6679765, ECO:0000269|Ref.5,
FT                   ECO:0000312|PDB:1SIS"
FT   DISULFID        16..31
FT                   /evidence="ECO:0000269|PubMed:6679765, ECO:0000269|Ref.5,
FT                   ECO:0000312|PDB:1SIS"
FT   DISULFID        20..33
FT                   /evidence="ECO:0000269|PubMed:6679765, ECO:0000269|Ref.5,
FT                   ECO:0000312|PDB:1SIS"
FT   HELIX           12..19
FT                   /evidence="ECO:0007829|PDB:1SIS"
FT   TURN            20..22
FT                   /evidence="ECO:0007829|PDB:1SIS"
FT   STRAND          24..27
FT                   /evidence="ECO:0007829|PDB:1SIS"
FT   STRAND          30..33
FT                   /evidence="ECO:0007829|PDB:1SIS"
SQ   SEQUENCE   35 AA;  3835 MW;  47D269810B64318F CRC64;
     MCMPCFTTDP NMAKKCRDCC GGNGKCFGPQ CLCNR