KAX11_LEIHE
ID KAX11_LEIHE Reviewed; 59 AA.
AC P13487;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 21-NOV-2003, sequence version 4.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Potassium channel toxin alpha-KTx 1.1;
DE AltName: Full=ChTX-Lq1 {ECO:0000303|PubMed:2477548};
DE AltName: Full=ChTx-a;
DE AltName: Full=Charybdotoxin {ECO:0000303|PubMed:2453055};
DE Short=CTX {ECO:0000303|PubMed:20007782};
DE Short=ChTX {ECO:0000303|PubMed:2453055};
DE Flags: Precursor;
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Single abdominal segment;
RX PubMed=9929387; DOI=10.1007/pl00006457;
RA Froy O., Sagiv T., Poreh M., Urbach D., Zilberberg N., Gurevitz M.;
RT "Dynamic diversification from a putative common ancestor of scorpion toxins
RT affecting sodium, potassium, and chloride channels.";
RL J. Mol. Evol. 48:187-196(1999).
RN [2]
RP PROTEIN SEQUENCE OF 23-59, PYROGLUTAMATE FORMATION AT GLN-23, AND
RP SUBCELLULAR LOCATION.
RX PubMed=2453055; DOI=10.1073/pnas.85.10.3329;
RA Gimenez-Gallego G., Navia M.A., Reuben J.P., Katz G.M., Kaczorowski G.J.,
RA Garcia M.L.;
RT "Purification, sequence, and model structure of charybdotoxin, a potent
RT selective inhibitor of calcium-activated potassium channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3329-3333(1988).
RN [3]
RP PROTEIN SEQUENCE OF 23-59, AND PYROGLUTAMATE FORMATION AT GLN-23.
RX PubMed=2482078; DOI=10.1021/bi00451a025;
RA Schweitz H., Bidard J.-N., Maes P., Lazdunski M.;
RT "Charybdotoxin is a new member of the K+ channel toxin family that includes
RT dendrotoxin I and mast cell degranulating peptide.";
RL Biochemistry 28:9708-9714(1989).
RN [4]
RP PROTEIN SEQUENCE OF 23-59, FUNCTION, AND PYROGLUTAMATE FORMATION AT GLN23.
RC TISSUE=Venom;
RX PubMed=2477548; DOI=10.1007/bf01870284;
RA Lucchesi K., Ravindran A., Young H., Moczydlowski E.;
RT "Analysis of the blocking activity of charybdotoxin homologs and iodinated
RT derivatives against Ca2+-activated K+ channels.";
RL J. Membr. Biol. 109:269-281(1989).
RN [5]
RP SYNTHESIS OF 23-59.
RX PubMed=1696475; DOI=10.1016/0006-291x(90)92145-p;
RA Lambert P., Kuroda H., Chino N., Watanabe T.X., Kimura T., Sakakibara S.;
RT "Solution synthesis of charybdotoxin (ChTX), a K+ channel blocker.";
RL Biochem. Biophys. Res. Commun. 170:684-690(1990).
RN [6]
RP SYNTHESIS OF 23-59, AND DISULFIDE BONDS.
RX PubMed=1699936; DOI=10.1016/s0021-9258(17)30573-2;
RA Sugg E.E., Garcia M.L., Reuben J.P., Patchett A.A., Kaczorowski G.J.;
RT "Synthesis and structural characterization of charybdotoxin, a potent
RT peptidyl inhibitor of the high conductance Ca2(+)-activated K+ channel.";
RL J. Biol. Chem. 265:18745-18748(1990).
RN [7]
RP FUNCTION.
RX PubMed=8204618; DOI=10.1021/bi00188a012;
RA Garcia M.L., Garcia-Calvo M., Hidalgo P., Lee A., Mackinnon R.;
RT "Purification and characterization of three inhibitors of voltage-dependent
RT K+ channels from Leiurus quinquestriatus var. hebraeus venom.";
RL Biochemistry 33:6834-6839(1994).
RN [8]
RP FUNCTION.
RX PubMed=7517498;
RA Grissmer S., Nguyen A.N., Aiyar J., Hanson D.C., Mather R.J., Gutman G.A.,
RA Karmilowicz M.J., Auperin D.D., Chandy K.G.;
RT "Pharmacological characterization of five cloned voltage-gated K+ channels,
RT types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell
RT lines.";
RL Mol. Pharmacol. 45:1227-1234(1994).
RN [9]
RP FUNCTION.
RX PubMed=12719233; DOI=10.1016/s0006-3495(03)70028-9;
RA Zhang M., Korolkova Y.V., Liu J., Jiang M., Grishin E.V., Tseng G.N.;
RT "BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but
RT the mechanism of action with ErgTx1.";
RL Biophys. J. 84:3022-3036(2003).
RN [10]
RP FUNCTION.
RX PubMed=12527813; DOI=10.1124/mol.63.2.409;
RA Castle N.A., London D.O., Creech C., Fajloun Z., Stocker J.W.,
RA Sabatier J.-M.;
RT "Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated
RT potassium channels.";
RL Mol. Pharmacol. 63:409-418(2003).
RN [11]
RP FUNCTION.
RX PubMed=15118082; DOI=10.1073/pnas.0401567101;
RA Yount N.Y., Yeaman M.R.;
RT "Multidimensional signatures in antimicrobial peptides.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7363-7368(2004).
RN [12]
RP FUNCTION.
RX PubMed=20007782; DOI=10.1073/pnas.0910123106;
RA Takacs Z., Toups M., Kollewe A., Johnson E., Cuello L.G., Driessens G.,
RA Biancalana M., Koide A., Ponte C.G., Perozo E., Gajewski T.F.,
RA Suarez-Kurtz G., Koide S., Goldstein S.A.;
RT "A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-
RT based library.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:22211-22216(2009).
RN [13]
RP FUNCTION.
RX PubMed=26817841; DOI=10.1074/jbc.m115.680611;
RA Meng L., Xie Z., Zhang Q., Li Y., Yang F., Chen Z., Li W., Cao Z., Wu Y.;
RT "Scorpion potassium channel-blocking defensin highlights a functional link
RT with neurotoxin.";
RL J. Biol. Chem. 291:7097-7106(2016).
RN [14]
RP FUNCTION, AND RECOMBINANT EXPRESSION.
RX PubMed=31276191; DOI=10.1002/1873-3468.13530;
RA Kasheverov I.E., Oparin P.B., Zhmak M.N., Egorova N.S., Ivanov I.A.,
RA Gigolaev A.M., Nekrasova O.V., Serebryakova M.V., Kudryavtsev D.S.,
RA Prokopev N.A., Hoang A.N., Tsetlin V.I., Vassilevski A.A., Utkin Y.N.;
RT "Scorpion toxins interact with nicotinic acetylcholine receptors.";
RL FEBS Lett. 593:2779-2789(2019).
RN [15]
RP STRUCTURE BY NMR OF 23-59, AND DISULFIDE BONDS.
RX PubMed=1696395; DOI=10.1126/science.1696395;
RA Massefski W. Jr., Redfield A.G., Hare D.R., Miller C.;
RT "Molecular structure of charybdotoxin, a pore-directed inhibitor of
RT potassium ion channels.";
RL Science 249:521-524(1990).
RN [16]
RP STRUCTURE BY NMR OF 23-59, AND DISULFIDE BONDS.
RX PubMed=1705886; DOI=10.1111/j.1432-1033.1991.tb15780.x;
RA Bontems F., Roumestand C., Boyot P., Gilquin B., Doljansky Y.;
RT "Three-dimensional structure of natural charybdotoxin in aqueous solution
RT by 1H-NMR. Charybdotoxin possesses a structural motif found in other
RT scorpion toxins.";
RL Eur. J. Biochem. 196:19-28(1991).
RN [17]
RP STRUCTURE BY NMR OF 23-59, AND DISULFIDE BONDS.
RX PubMed=1720574; DOI=10.1126/science.1720574;
RA Bontems F., Roumestand C., Gilquin B., Menez A., Toma F.;
RT "Refined structure of charybdotoxin: common motifs in scorpion toxins and
RT insect defensins.";
RL Science 254:1521-1523(1991).
RN [18]
RP STRUCTURE BY NMR OF 23-59, AND DISULFIDE BONDS.
RX PubMed=1380828; DOI=10.1021/bi00149a003;
RA Bontems F., Gilquin B., Roumestand C., Menez A., Toma F.;
RT "Analysis of side-chain organization on a refined model of charybdotoxin:
RT structural and functional implications.";
RL Biochemistry 31:7756-7764(1992).
RN [19]
RP STRUCTURE BY NMR OF 23-59, AND DISULFIDE BONDS.
RX PubMed=1467342; DOI=10.1016/0300-9084(92)90065-m;
RA Bonmatin J.-M., Genest M., Petit M.-C., Gincel E., Simorre J.-P.,
RA Cornet B., Gallet X., Caille A., Labbe H., Vovelle F., Ptak M.;
RT "Progress in multidimensional NMR investigations of peptide and protein 3-D
RT structures in solution. From structure to functional aspects.";
RL Biochimie 74:825-836(1992).
RN [20]
RP STRUCTURE BY NMR OF 23-59, AND DISULFIDE BONDS.
RX PubMed=9092804; DOI=10.1021/bi962720h;
RA Song J., Gilquin B., Jamin N., Drakopoulou E., Guenneugues M., Dauplais M.,
RA Vita C., Menez A.;
RT "NMR solution structure of a two-disulfide derivative of charybdotoxin:
RT structural evidence for conservation of scorpion toxin alpha/beta motif and
RT its hydrophobic side chain packing.";
RL Biochemistry 36:3760-3766(1997).
CC -!- FUNCTION: This toxin inhibits numerous potassium channels: shaker
CC (Ki=227 nM), Kv1.2/KCNA2 (nanomolar range), Kv1.3/KCNA3 (nanomolar
CC range), Kv1.5/KCNA5 (Kd>100 nM), Kv1.6/KCNA6 (Ki=22 nM), KCa1.1/KCNMA1
CC (IC(50)=5.9 nM). It blocks channel activity by a simple bimolecular
CC inhibition process. It also shows a weak interaction with nicotinic
CC acetylcholine receptors (nAChR), suggesting it may weakly inhibit it
CC (PubMed:31276191). It also exhibits pH-specific antimicrobial
CC activities against bacteria (B.subtilis, E.coli and S.aureus) and the
CC fungus C.albicans (PubMed:15118082). {ECO:0000269|PubMed:12527813,
CC ECO:0000269|PubMed:15118082, ECO:0000269|PubMed:20007782,
CC ECO:0000269|PubMed:2477548, ECO:0000269|PubMed:31276191,
CC ECO:0000269|PubMed:7517498, ECO:0000269|PubMed:8204618}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2453055}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:2453055}.
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:1696395}.
CC -!- MISCELLANEOUS: This toxin does not or very weakly inhibits Kv1.1/KCNA1,
CC Kv2.1/KCNB1 (Ki>2 uM), Kv3.1/KCNC1 (Kd>1 uM), Kv11.1/KCNH2,
CC KCa2.1/KCNN1 (IC(50)> 1 uM), KCa2.2/ KCNN2 (IC(50)> 1 uM), KCa2.3/
CC KCNN3 (IC(50)> 1 uM) (PubMed:12527813, PubMed:12719233,
CC PubMed:20007782, PubMed:7517498, PubMed:8204618). Does not inhibit the
CC growth of Gram-positive and Gram-negative bacteria (PubMed:26817841).
CC {ECO:0000269|PubMed:12527813, ECO:0000269|PubMed:12719233,
CC ECO:0000269|PubMed:20007782, ECO:0000269|PubMed:26817841,
CC ECO:0000269|PubMed:7517498, ECO:0000269|PubMed:8204618}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 01 subfamily. {ECO:0000305}.
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DR PIR; A28202; A60963.
DR PDB; 1BAH; NMR; -; A=24-59.
DR PDB; 1CMR; NMR; -; A=29-59.
DR PDB; 2A9H; NMR; -; E=24-59.
DR PDB; 2CRD; NMR; -; A=24-59.
DR PDB; 4JTA; X-ray; 2.50 A; Y=23-59.
DR PDB; 4JTC; X-ray; 2.56 A; Y=23-59.
DR PDB; 4JTD; X-ray; 2.54 A; Y=23-59.
DR PDBsum; 1BAH; -.
DR PDBsum; 1CMR; -.
DR PDBsum; 2A9H; -.
DR PDBsum; 2CRD; -.
DR PDBsum; 4JTA; -.
DR PDBsum; 4JTC; -.
DR PDBsum; 4JTD; -.
DR AlphaFoldDB; P13487; -.
DR BMRB; P13487; -.
DR SMR; P13487; -.
DR EvolutionaryTrace; P13487; -.
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 GO; GO:0042742; P:defense response to bacterium; 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 Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR001947; Scorpion_toxinS_K_inh.
DR Pfam; PF00451; Toxin_2; 1.
DR PRINTS; PR00286; CHARYBDTOXIN.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial;
KW Calcium-activated potassium channel impairing toxin;
KW Direct protein sequencing; Disulfide bond; Fungicide;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Pyrrolidone carboxylic acid; Secreted; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:2453055,
FT ECO:0000269|PubMed:2477548, ECO:0000269|PubMed:2482078"
FT CHAIN 23..59
FT /note="Potassium channel toxin alpha-KTx 1.1"
FT /evidence="ECO:0000269|PubMed:2453055,
FT ECO:0000269|PubMed:2477548, ECO:0000269|PubMed:2482078"
FT /id="PRO_0000035307"
FT REGION 48..55
FT /note="Interaction with Ca(2+)-activated K(+) channels"
FT /evidence="ECO:0000255"
FT SITE 49
FT /note="Basic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT SITE 58
FT /note="Aromatic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT MOD_RES 23
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:2453055,
FT ECO:0000269|PubMed:2482078"
FT DISULFID 29..50
FT /evidence="ECO:0000269|PubMed:1380828,
FT ECO:0000269|PubMed:1467342, ECO:0000269|PubMed:1696395,
FT ECO:0000269|PubMed:1699936, ECO:0000269|PubMed:1705886,
FT ECO:0000269|PubMed:1720574, ECO:0000269|PubMed:9092804"
FT DISULFID 35..55
FT /evidence="ECO:0000269|PubMed:1380828,
FT ECO:0000269|PubMed:1467342, ECO:0000269|PubMed:1696395,
FT ECO:0000269|PubMed:1699936, ECO:0000269|PubMed:1705886,
FT ECO:0000269|PubMed:1720574, ECO:0000269|PubMed:9092804"
FT DISULFID 39..57
FT /evidence="ECO:0000269|PubMed:1380828,
FT ECO:0000269|PubMed:1467342, ECO:0000269|PubMed:1696395,
FT ECO:0000269|PubMed:1699936, ECO:0000269|PubMed:1705886,
FT ECO:0000269|PubMed:1720574, ECO:0000269|PubMed:9092804"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:4JTA"
FT HELIX 36..42
FT /evidence="ECO:0007829|PDB:4JTA"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:2CRD"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:1BAH"
SQ SEQUENCE 59 AA; 6674 MW; 379227EBBCB21947 CRC64;
MKILSVLLLA LIICSIVGWS EAQFTNVSCT TSKECWSVCQ RLHNTSRGKC MNKKCRCYS
