ID   KAX83_LEIHE             Reviewed;          29 AA.
AC   P80670;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   22-FEB-2023, entry version 76.
DE   RecName: Full=Potassium channel toxin alpha-KTx 8.3 {ECO:0000305};
DE   AltName: Full=Gating modifier of anion channels 2 {ECO:0000303|PubMed:19574231};
DE            Short=Toxin GaTx2 {ECO:0000303|PubMed:19574231};
DE   AltName: Full=Leiuropeptide II {ECO:0000303|PubMed:9266482};
DE            Short=LpII;
DE   AltName: Full=Leiuropeptide-2 {ECO:0000305};
OS   Leiurus hebraeus (Deathstalker scorpion) (Leiurus quinquestriatus
OS   hebraeus).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Buthida; Buthoidea; Buthidae; Leiurus.
OX   NCBI_TaxID=6884;
RN   [1]
RP   PROTEIN SEQUENCE, STRUCTURE BY NMR, DISULFIDE BONDS, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Venom;
RX   PubMed=9266482; DOI=10.1111/j.1399-3011.1997.tb01162.x;
RA   Buisine E., Wieruszeski J.-M., Lippens G., Wouters D., Tartar A.,
RA   Sautiere P.;
RT   "Characterization of a new family of toxin-like peptides from the venom of
RT   the scorpion Leiurus quinquestriatus hebraeus. 1H-NMR structure of
RT   leiuropeptide II.";
RL   J. Pept. Res. 49:545-555(1997).
RN   [2]
RP   PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, AND MASS SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=19574231; DOI=10.1074/jbc.m109.031724;
RA   Thompson C.H., Olivetti P.R., Fuller M.D., Freeman C.S., McMaster D.,
RA   French R.J., Pohl J., Kubanek J., McCarty N.A.;
RT   "Isolation and characterization of a high affinity peptide inhibitor of
RT   ClC-2 chloride channels.";
RL   J. Biol. Chem. 284:26051-26062(2009).
RN   [3]
RP   FUNCTION.
RX   PubMed=16596447; DOI=10.1007/s00232-005-0818-8;
RA   Thompson C.H., Fields D.M., Olivetti P.R., Fuller M.D., Zhang Z.R.,
RA   Kubanek J., McCarty N.A.;
RT   "Inhibition of ClC-2 chloride channels by a peptide component or components
RT   of scorpion venom.";
RL   J. Membr. Biol. 208:65-76(2005).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=16551474; DOI=10.1016/j.toxicon.2006.01.015;
RA   Nascimento D.G., Rates B., Santos D.M., Verano-Braga T., Barbosa-Silva A.,
RA   Dutra A.A.A., Biondi I., Martin-Eauclaire M.-F., De Lima M.E.,
RA   Pimenta A.M.C.;
RT   "Moving pieces in a taxonomic puzzle: venom 2D-LC/MS and data clustering
RT   analyses to infer phylogenetic relationships in some scorpions from the
RT   Buthidae family (Scorpiones).";
RL   Toxicon 47:628-639(2006).
CC   -!- FUNCTION: Specific and potent inhibitor of ClC-2/CLCN2 chloride
CC       channel. It slows ClC-2/CLCN2 activation by increasing the latency to
CC       first opening by nearly 8-fold but is unable to inhibit open channels,
CC       suggesting that this toxin inhibits channel activation gating.
CC       {ECO:0000269|PubMed:16596447, ECO:0000269|PubMed:19574231}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9266482}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:9266482}.
CC   -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC       beta-sheet by disulfide bonds (CSalpha/beta).
CC       {ECO:0000269|PubMed:9266482}.
CC   -!- MASS SPECTROMETRY: Mass=3191.29; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:19574231};
CC   -!- MISCELLANEOUS: Negative results: does not inhibit ClC-0, ClC-1/CLCN1,
CC       ClC-3/CLCN3, ClC-4/CLCN4, CFTR chloride channel, GABRR, calcium-
CC       activated chloride channel regulator (Cl(Ca)), Shaker, and Kv1.2/KCNA2.
CC       {ECO:0000269|PubMed:19574231}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor family. Alpha-KTx 08 subfamily.
CC       {ECO:0000269|PubMed:9266482}.
CC   -!- CAUTION: Has sequence similarities with potassium channel inhibitors,
CC       but inhibits chloride channels. It is why the systematic name
CC       'Potassium channel toxin alpha-KTx 8.3' has been moved as alternative
CC       name. {ECO:0000305}.
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DR   AlphaFoldDB; P80670; -.
DR   SMR; P80670; -.
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:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR036574; Scorpion_toxin-like_sf.
DR   InterPro; IPR008911; Toxin_alpha-KTx_8/9.
DR   Pfam; PF05453; Toxin_6; 1.
DR   SUPFAM; SSF57095; Scorpion toxin-like; 1.
PE   1: Evidence at protein level;
KW   Chloride channel impairing toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated chloride channel impairing toxin.
FT   PEPTIDE         1..29
FT                   /note="Potassium channel toxin alpha-KTx 8.3"
FT                   /evidence="ECO:0000269|PubMed:19574231,
FT                   ECO:0000269|PubMed:9266482"
FT                   /id="PRO_0000044542"
FT   DISULFID        3..19
FT                   /evidence="ECO:0000269|PubMed:9266482"
FT   DISULFID        6..24
FT                   /evidence="ECO:0000269|PubMed:9266482"
FT   DISULFID        10..26
FT                   /evidence="ECO:0000269|PubMed:9266482"
SQ   SEQUENCE   29 AA;  3199 MW;  BC5F650C196C15B8 CRC64;
     VSCEDCPDHC STQKARAKCD NDKCVCEPI
//