ID   KKX13_HETSP             Reviewed;          23 AA.
AC   P83655;
DT   07-DEC-2004, integrated into UniProtKB/Swiss-Prot.
DT   07-DEC-2004, sequence version 1.
DT   25-MAY-2022, entry version 39.
DE   RecName: Full=Potassium channel toxin kappa-KTx 1.3 {ECO:0000303|PubMed:15670585};
DE   AltName: Full=Kappa-hefutoxin 3 {ECO:0000303|PubMed:27578329};
OS   Heterometrus spinifer (Asia giant forest scorpion) (Malaysian black
OS   scorpion).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC   Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Heterometrinae;
OC   Heterometrus.
OX   NCBI_TaxID=118530;
RN   [1]
RP   PROTEIN SEQUENCE, SUBUNIT, SUBCELLULAR LOCATION, DISULFIDE BOND,
RP   MUTAGENESIS OF LYS-20, MASS SPECTROMETRY, SYNTHESIS, AND 3D-STRUCTURE
RP   MODELING.
RC   TISSUE=Venom;
RX   PubMed=15670585; DOI=10.1016/j.bcp.2004.10.018;
RA   Nirthanan S., Pil J., Abdel-Mottaleb Y., Sugahara Y., Gopalakrishnakone P.,
RA   Joseph J.S., Sato K., Tytgat J.;
RT   "Assignment of voltage-gated potassium channel blocking activity to kappa-
RT   KTx1.3, a non-toxic homologue of kappa-hefutoxin-1, from Heterometrus
RT   spinifer venom.";
RL   Biochem. Pharmacol. 69:669-678(2005).
RN   [2]
RP   FUNCTION.
RX   PubMed=27578329; DOI=10.1016/j.peptides.2016.08.008;
RA   Moreels L., Peigneur S., Yamaguchi Y., Vriens K., Waelkens E., Zhu S.,
RA   Thevissen K., Cammue B.P.A., Sato K., Tytgat J.;
RT   "Expanding the pharmacological profile of kappa-hefutoxin 1 and analogues:
RT   A focus on the inhibitory effect on the oncogenic channel Kv10.1.";
RL   Peptides 98:43-50(2017).
CC   -!- FUNCTION: Shows very weak blocking activity on voltage-gated potassium
CC       channels Kv10.1/KCNH1/EAG1 (6.2% inhibition by 40 uM of the toxin)
CC       (PubMed:27578329). Has no effect on the other voltage-gated potassium
CC       channels tested (PubMed:15670585). {ECO:0000269|PubMed:15670585,
CC       ECO:0000269|PubMed:27578329}.
CC   -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:15670585}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15670585}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:15670585}.
CC   -!- DOMAIN: Has the structural arrangement of two alpha-helices stabilized
CC       by disulfide bonds (CSalpha/alpha 2(S-S)).
CC       {ECO:0000250|UniProtKB:P82851}.
CC   -!- PTM: Is not amidated. {ECO:0000269|PubMed:15670585}.
CC   -!- MASS SPECTROMETRY: Mass=2620.7; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:15670585};
CC   -!- MISCELLANEOUS: Has no effect on Kv1.1/KCNA1, Kv1.2/KCNA2 and
CC       Kv1.3/KCNA3 potassium channels, suggesting that the presence of an
CC       additional charged residue in a position adjacent to the dyad lysine
CC       impedes the functional block of Kv1 channels produced by this toxin.
CC       {ECO:0000269|PubMed:15670585}.
CC   -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC       channel inhibitor kappa-KTx family. Kappa-KTx 1 subfamily.
CC       {ECO:0000305}.
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DR   AlphaFoldDB; P83655; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0015459; F:potassium channel regulator activity; IEA:UniProtKB-KW.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR012630; Toxin_25.
DR   Pfam; PF08095; Toxin_25; 1.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW   Potassium channel impairing toxin; Secreted; Toxin;
KW   Voltage-gated potassium channel impairing toxin.
FT   PEPTIDE         1..23
FT                   /note="Potassium channel toxin kappa-KTx 1.3"
FT                   /evidence="ECO:0000269|PubMed:15670585"
FT                   /id="PRO_0000044546"
FT   SITE            5
FT                   /note="Aromatic residue of the functional dyad"
FT                   /evidence="ECO:0000250|UniProtKB:P82851"
FT   SITE            19
FT                   /note="Basic residue of the functional dyad"
FT                   /evidence="ECO:0000250|UniProtKB:P82851"
FT   DISULFID        4..22
FT                   /evidence="ECO:0000269|PubMed:15670585"
FT   DISULFID        8..18
FT                   /evidence="ECO:0000269|PubMed:15670585"
FT   MUTAGEN         20
FT                   /note="K->A: Blocks both Kv1.2/KCNA2 (IC(50)=36.9 uM) and
FT                   Kv1.3/KCNA3 (IC(50)=115.7 uM) but also Kv1.1/KCNA1
FT                   (IC(50)=110.7 uM)."
FT                   /evidence="ECO:0000269|PubMed:15670585"
FT   MUTAGEN         20
FT                   /note="K->E: Blocks Kv1.2/KCNA2 (IC(50)=36.8 uM) and
FT                   Kv1.3/KCNA3 (IC(50)=53.7 uM), but not Kv1.1/KCNA1."
FT                   /evidence="ECO:0000269|PubMed:15670585"
FT   MUTAGEN         20
FT                   /note="K->R: Does not block any channel subtype tested."
FT                   /evidence="ECO:0000269|PubMed:15670585"
SQ   SEQUENCE   23 AA;  2625 MW;  AE059DD3CA5D61CE CRC64;
     GFGCYRSCWK AGHDEETCKK ECS