KAX51_LEIHE
ID KAX51_LEIHE Reviewed; 31 AA.
AC P16341;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Potassium channel toxin alpha-KTx 5.1;
DE AltName: Full=Leiurotoxin I {ECO:0000303|PubMed:2153586, ECO:0000303|PubMed:2307683, ECO:0000303|PubMed:2839478};
DE Short=LeTx I;
DE Short=Lei-I;
DE AltName: Full=Leiurotoxin-1 {ECO:0000305};
DE AltName: Full=Scyllatoxin {ECO:0000303|PubMed:2153586, ECO:0000303|PubMed:2307683};
DE Short=ScyTx;
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, FUNCTION, AMIDATION AT HIS-31, AND SUBUNIT.
RC TISSUE=Venom;
RX PubMed=2839478; DOI=10.1016/s0021-9258(19)81496-5;
RA Chicci G.G., Gimenez-Gallego G., Ber E., Garcia M.L., Winquist R.,
RA Cascieri M.A.;
RT "Purification and characterization of a unique, potent inhibitor of apamin
RT binding from Leiurus quinquestriatus hebraeus venom.";
RL J. Biol. Chem. 263:10192-10197(1988).
RN [2]
RP FUNCTION, AND SYNTHESIS.
RX PubMed=2307683; DOI=10.1016/s0021-9258(19)39626-7;
RA Auguste P., Hugues M., Grave B., Gesquiere J.C., Maes P., Tartar A.,
RA Romey G., Schweitz H., Lazdunski M.;
RT "Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+
RT channels. Chemical synthesis, radiolabeling, and receptor
RT characterization.";
RL J. Biol. Chem. 265:4753-4759(1990).
RN [3]
RP FUNCTION, MUTAGENESIS OF ARG-6 AND 6-MET-ARG-7, AND SITES ALA-1; PHE-6;
RP ARG-7 AND VAL-24.
RX PubMed=11527975; DOI=10.1074/jbc.m106981200;
RA Shakkottai V.G., Regaya I., Wulff H., Fajloun Z., Tomita H., Fathallah M.,
RA Cahalan M.D., Gargus J.J., Sabatier J.M., Chandy K.G.;
RT "Design and characterization of a highly selective peptide inhibitor of the
RT small conductance calcium-activated K+ channel, SkCa2.";
RL J. Biol. Chem. 276:43145-43151(2001).
RN [4]
RP SYNTHESIS, AND NUMBER OF DISULFIDE BONDS REQUIRED FOR ACTIVITY.
RX PubMed=12234192; DOI=10.1021/bi026136m;
RA Zhu Q., Liang S., Martin L., Gasparini S., Menez A., Vita C.;
RT "Role of disulfide bonds in folding and activity of leiurotoxin I: just two
RT disulfides suffice.";
RL Biochemistry 41:11488-11494(2002).
RN [5]
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).
RN [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=2153586; DOI=10.1016/0014-5793(90)80115-y;
RA Martins J.C., Zhang W., Tartar A., Lazdunski M., Borremans F.A.M.;
RT "Solution conformation of leiurotoxin I (scyllatoxin) by 1H nuclear
RT magnetic resonance. Resonance assignment and secondary structure.";
RL FEBS Lett. 260:249-253(1990).
CC -!- FUNCTION: Blocker for the small conductance calcium-activated potassium
CC channels (PubMed:2839478, PubMed:2307683, PubMed:11527975). Shows the
CC best affinity for KCa2.2/KCNN2 (Kd=0.2 nM), followed by KCa2.3/KCNN3
CC (Kd=1.1 nM) and KCa2.1/KCNN1 (Kd=325 nM) (PubMed:11527975).
CC {ECO:0000269|PubMed:11527975, ECO:0000269|PubMed:2307683,
CC ECO:0000269|PubMed:2839478}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2839478}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2839478}.
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:2153586}.
CC -!- PTM: Two disulfide bonds are the minimal requirement needed to produce
CC a nativelike and bio-active conformation in this toxin. The third
CC disulfide provides an additional contribution to structure
CC stabilization and can modulate biological potency depending on its
CC position and the structural regions involved in biological activity.
CC {ECO:0000269|PubMed:12234192}.
CC -!- MISCELLANEOUS: A mutant [R7diaminobutanoic acid] has been developed
CC that discriminates KCa2.2/KCNN2 (Kd=3.8 nM) from KCa2.3/KCNN3 (Kd=2500
CC nM). {ECO:0000269|PubMed:11527975}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 05 subfamily. {ECO:0000305}.
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DR PIR; A28805; A28805.
DR PDB; 1SCY; NMR; -; A=1-31.
DR PDBsum; 1SCY; -.
DR AlphaFoldDB; P16341; -.
DR BMRB; P16341; -.
DR SMR; P16341; -.
DR EvolutionaryTrace; P16341; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0015459; F:potassium 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; IPR001947; Scorpion_toxinS_K_inh.
DR Pfam; PF00451; Toxin_2; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation;
KW Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Secreted; Toxin.
FT PEPTIDE 1..31
FT /note="Potassium channel toxin alpha-KTx 5.1"
FT /evidence="ECO:0000269|PubMed:2839478"
FT /id="PRO_0000044924"
FT REGION 6..9
FT /note="[R/K]XCQ motif"
FT /evidence="ECO:0000305"
FT SITE 1
FT /note="Interacts with KCa2.2/KCNN2 and KCa2.3/KCNN3"
FT /evidence="ECO:0000305|PubMed:11527975"
FT SITE 2
FT /note="Interacts with KCa2.2/KCNN2 and KCa2.3/KCNN3"
FT /evidence="ECO:0000305|PubMed:11527975"
FT SITE 7
FT /note="Interacts with KCa2.2/KCNN2 and KCa2.3/KCNN3"
FT /evidence="ECO:0000305|PubMed:11527975"
FT SITE 24
FT /note="Interacts with KCa2.2/KCNN2 and KCa2.3/KCNN3"
FT /evidence="ECO:0000305|PubMed:11527975"
FT MOD_RES 31
FT /note="Histidine amide"
FT /evidence="ECO:0000269|PubMed:2839478"
FT DISULFID 3..21
FT /evidence="ECO:0000269|PubMed:2153586,
FT ECO:0000269|PubMed:2307683, ECO:0000312|PDB:1SCY"
FT DISULFID 8..26
FT /evidence="ECO:0000269|PubMed:2153586,
FT ECO:0000269|PubMed:2307683, ECO:0000312|PDB:1SCY"
FT DISULFID 12..28
FT /evidence="ECO:0000269|PubMed:2153586,
FT ECO:0000269|PubMed:2307683, ECO:0000312|PDB:1SCY"
FT MUTAGEN 6..7
FT /note="RM->MR: 50-fold and 60-fold decrease in potency of
FT inhibition of KCa2.2/KCNN2 and KCa2.3/KCNN3, respectively."
FT /evidence="ECO:0000269|PubMed:11527975"
FT MUTAGEN 6
FT /note="R->K: 20-fold and 30-fold decrease in potency of
FT inhibition of KCa2.2/KCNN2 and KCa2.3/KCNN3, respectively."
FT /evidence="ECO:0000269|PubMed:11527975"
FT MUTAGEN 6
FT /note="R->L: 75-fold and 165-fold decrease in potency of
FT inhibition of KCa2.2/KCNN2 and KCa2.3/KCNN3, respectively."
FT /evidence="ECO:0000269|PubMed:11527975"
FT HELIX 5..14
FT /evidence="ECO:0007829|PDB:1SCY"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:1SCY"
FT STRAND 23..29
FT /evidence="ECO:0007829|PDB:1SCY"
SQ SEQUENCE 31 AA; 3430 MW; BB3183DC5CEA53A7 CRC64;
AFCNLRMCQL SCRSLGLLGK CIGDKCECVK H
