KKX11_CHEFU
ID KKX11_CHEFU Reviewed; 23 AA.
AC P82851; P82850;
DT 04-MAY-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 25-MAY-2022, entry version 72.
DE RecName: Full=Potassium channel toxin kappa-KTx 1.2 {ECO:0000303|PubMed:15670585};
DE AltName: Full=Kappa-hefutoxin 2 {ECO:0000303|PubMed:12034709};
DE Short=Kappa-HfTx2 {ECO:0000303|PubMed:12034709};
DE Contains:
DE RecName: Full=Potassium channel toxin kappa-KTx 1.1 {ECO:0000303|PubMed:15670585};
DE AltName: Full=Kappa-hefutoxin 1 {ECO:0000303|PubMed:12034709};
DE Short=Kappa-HfTx1 {ECO:0000305|PubMed:12034709};
OS Chersonesometrus fulvipes (Indian black scorpion) (Heterometrus fulvipes).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Heterometrinae;
OC Chersonesometrus.
OX NCBI_TaxID=141248;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, AMIDATION AT CYS-22, STRUCTURE BY NMR OF 1-22,
RP DISULFIDE BONDS, SUBCELLULAR LOCATION, MASS SPECTROMETRY, MUTAGENESIS OF
RP TYR-5 AND LYS-19, AND SITES TYR-5 AND LYS-19 (FUNCTIONAL DYAD).
RC TISSUE=Venom;
RX PubMed=12034709; DOI=10.1074/jbc.m111258200;
RA Srinivasan K.N., Sivaraja V., Huys I., Sasaki T., Cheng B., Kumar T.K.S.,
RA Sato K., Tytgat J., Yu C., San B.C.C., Ranganathan S., Bowie H.J.,
RA Kini R.M., Gopalakrishnakone P.;
RT "Kappa-hefutoxin1, a novel toxin from the scorpion Heterometrus fulvipes
RT with unique structure and function. Importance of the functional diad in
RT potassium channel selectivity.";
RL J. Biol. Chem. 277:30040-30047(2002).
RN [2]
RP FUNCTION, SYNTHESIS OF 1-22, AND MUTAGENESIS OF GLY-1; 1-GLY-HIS-2 AND
RP 1-GLY--ALA-3.
RX PubMed=23726856; DOI=10.1016/j.toxicon.2013.05.010;
RA Peigneur S., Yamaguchi Y., Goto H., Srinivasan K.N., Gopalakrishnakone P.,
RA Tytgat J., Sato K.;
RT "Synthesis and characterization of amino acid deletion analogs of kappa-
RT hefutoxin 1, a scorpion toxin on potassium channels.";
RL Toxicon 71:25-30(2013).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF GLY-1 AND 1-GLY-HIS-2.
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).
RN [4]
RP NOMENCLATURE.
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 [5]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-22, SYNTHESIS OF 1-22, AND
RP DISULFIDE 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: [Potassium channel toxin kappa-KTx 1.1]: Shows weak blocking
CC activity on voltage-gated potassium channels Kv10.1/KCNH1/EAG1
CC (IC(50)=26 uM), Kv1.2/KCNA2 (Kd=150 uM), Kv1.3/KCNA3 (Kd=40 uM),
CC Kv1.6/KCNA3 (16.6% inhibition at 40 uM toxin) (PubMed:12034709,
CC PubMed:23726856, PubMed:27578329). The block is dose-dependent,
CC voltage-independent, and reversible (PubMed:12034709). Also shows a
CC weak inhibitory activity on the plant pathogen F.culmorum growth
CC (IC(50)=18.8-37.7 uM) (PubMed:27578329). {ECO:0000269|PubMed:12034709,
CC ECO:0000269|PubMed:23726856, ECO:0000269|PubMed:27578329}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12034709}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:12034709}.
CC -!- DOMAIN: Has the structural arrangement of two alpha-helices stabilized
CC by disulfide bonds (CSalpha/alpha 2(S-S)).
CC {ECO:0000269|PubMed:12034709}.
CC -!- PTM: The two disulfide isomers globular (C1-C3, C2-C4) and beads (C1-
CC C2, C3-C4) do not show activity on Kv10.1/KCNH1/EAG1.
CC {ECO:0000269|PubMed:27578329}.
CC -!- MASS SPECTROMETRY: [Potassium channel toxin kappa-KTx 1.1]:
CC Mass=2655.4; Mass_error=0.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12034709};
CC -!- MASS SPECTROMETRY: [Potassium channel toxin kappa-KTx 1.2]:
CC Mass=2713.3; Mass_error=0.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:12034709};
CC -!- MISCELLANEOUS: Kappa-KTx 1.1 has no activity on Kv1.1/KCNA1 (Kd>>150
CC uM), Kv1.4/KCNA4, Kv1.5/KCNA5, shaker IR, Kv2.1/KCNB1, Kv3.1/KCNC1,
CC Kv4.2/KCND2, and Kv11.1/KCNH2/ERG1 (PubMed:12034709, PubMed:23726856).
CC Kappa-KTx 1.1 is not able to inhibit the growth of C.albicans,
CC S.cerevisiae or F.oxysporum (PubMed:27578329). Kappa-KTx 1.2 has no
CC activity on Kv10.1/KCNH1/EAG1 (PubMed:27578329).
CC {ECO:0000269|PubMed:12034709, ECO:0000269|PubMed:23726856}.
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 PDB; 1HP9; NMR; -; A=1-22.
DR PDB; 6ATS; X-ray; 1.90 A; A=1-23.
DR PDBsum; 1HP9; -.
DR PDBsum; 6ATS; -.
DR AlphaFoldDB; P82851; -.
DR SMR; P82851; -.
DR TCDB; 8.B.2.1.1; the short scorpion toxin (s-st) superfamily.
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 GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
DR InterPro; IPR012630; Toxin_25.
DR Pfam; PF08095; Toxin_25; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Fungicide; Ion channel impairing toxin; Neurotoxin;
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 1.2"
FT /evidence="ECO:0000269|PubMed:12034709"
FT /id="PRO_0000044544"
FT PEPTIDE 1..22
FT /note="Potassium channel toxin kappa-KTx 1.1"
FT /evidence="ECO:0000269|PubMed:12034709"
FT /id="PRO_0000446337"
FT SITE 5
FT /note="Aromatic residue of the functional dyad"
FT /evidence="ECO:0000269|PubMed:12034709"
FT SITE 19
FT /note="Basic residue of the functional dyad"
FT /evidence="ECO:0000269|PubMed:12034709"
FT MOD_RES 22
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:12034709"
FT DISULFID 4..22
FT /evidence="ECO:0000269|PubMed:12034709,
FT ECO:0007744|PDB:1HP9, ECO:0007744|PDB:6ATS"
FT DISULFID 8..18
FT /evidence="ECO:0000269|PubMed:12034709,
FT ECO:0007744|PDB:1HP9, ECO:0007744|PDB:6ATS"
FT MUTAGEN 1..3
FT /note="Missing: Loss of ability to block Kv1.2/KCNA2, and
FT decrease in ability to block Kv1.3/KCNA3 and Kv1.6/KCNA6."
FT /evidence="ECO:0000269|PubMed:23726856"
FT MUTAGEN 1..2
FT /note="Missing: Loss of ability to block Kv1.2/KCNA2, and
FT decrease in ability to block Kv1.3/KCNA3, Kv1.6/KCNA6, and
FT Kv10.1/KCNH1/EAG1."
FT /evidence="ECO:0000269|PubMed:23726856,
FT ECO:0000269|PubMed:27578329"
FT MUTAGEN 1
FT /note="Missing: Loss of ability to block Kv1.2/KCNA2, and
FT decrease in ability to block Kv1.3/KCNA3, Kv1.6/KCNA6, and
FT Kv10.1/KCNH1/EAG1."
FT /evidence="ECO:0000269|PubMed:23726856,
FT ECO:0000269|PubMed:27578329"
FT MUTAGEN 5
FT /note="Y->A: Loss of ability to block Kv1.2/KCNA2,
FT Kv1.3/KCNA3, and Kv10.1/KCNH1/EAG1 potassium channels
FT (kappa-Ktx1.1 mutated). Same effect observed; when
FT associated with A-19 (kappa-Ktx1.1 mutated)."
FT /evidence="ECO:0000269|PubMed:12034709"
FT MUTAGEN 19
FT /note="K->A: Loss of ability to block Kv1.2/KCNA2,
FT Kv1.3/KCNA3, and Kv10.1/KCNH1/EAG1 potassium channels
FT (kappa-Ktx1.1 mutated). Same effect observed; when
FT associated with A-5 (kappa-Ktx1.1 mutated)."
FT /evidence="ECO:0000269|PubMed:12034709"
FT HELIX 1..10
FT /evidence="ECO:0007829|PDB:6ATS"
FT HELIX 15..21
FT /evidence="ECO:0007829|PDB:6ATS"
SQ SEQUENCE 23 AA; 2717 MW; A61FB555EB877C6E CRC64;
GHACYRNCWR EGNDEETCKE RCG
