KAX62_SCOPA
ID KAX62_SCOPA Reviewed; 34 AA.
AC P80719;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 25-MAY-2022, entry version 116.
DE RecName: Full=Potassium channel toxin alpha-KTx 6.2;
DE AltName: Full=Maurotoxin {ECO:0000303|PubMed:9022673};
DE Short=MTX {ECO:0000303|PubMed:9022673};
OS Scorpio palmatus (Israeli golden scorpion) (Scorpio maurus palmatus).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Scorpioninae; Scorpio.
OX NCBI_TaxID=1662106;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SYNTHESIS, DISULFIDE BONDS, TOXIC DOSE, AND
RP SUBUNIT.
RX PubMed=9022673; DOI=10.1111/j.1432-1033.1996.0491r.x;
RA Kharrat R., Mabrouk K., Crest M., Darbon H., Oughideni R.,
RA Martin-Eauclaire M.-F., Jacquet G., el Ayeb M., van Rietschoten J.,
RA Rochat H., Sabatier J.-M.;
RT "Chemical synthesis and characterization of maurotoxin, a short scorpion
RT toxin with four disulfide bridges that acts on K+ channels.";
RL Eur. J. Biochem. 242:491-498(1996).
RN [2]
RP PROTEIN SEQUENCE, FUNCTION, SYNTHESIS, DISULFIDE BONDS, AND TOXIC DOSE.
RC TISSUE=Venom;
RX PubMed=9136903; DOI=10.1016/s0014-5793(97)00285-8;
RA Kharrat R., Mansuelle P., Sampieri F., Crest M., Oughideni R.,
RA Van Rietschoten J., Martin-Eauclaire M.-F., Rochat H., El Ayeb M.;
RT "Maurotoxin, a four disulfide bridge toxin from Scorpio maurus venom:
RT purification, structure and action on potassium channels.";
RL FEBS Lett. 406:284-290(1997).
RN [3]
RP SYNTHESIS, AMIDATION AT CYS-34, AND DISULFIDE BONDS.
RX PubMed=9792177; DOI=10.1016/s0041-0101(98)00153-6;
RA Rochat H., Kharrat R., Sabatier J.-M., Mansuelle P., Crest M.,
RA Martin-Eauclaire M.-F., Sampieri F., Oughideni R., Mabrouk K., Jacquet G.,
RA Van Rietschoten J., El Ayeb M.;
RT "Maurotoxin, a four disulfide bridges scorpion toxin acting on K+
RT channels.";
RL Toxicon 36:1609-1611(1998).
RN [4]
RP FUNCTION.
RX PubMed=10920011; DOI=10.1016/s0006-3495(00)76335-1;
RA Avdonin V., Nolan B., Sabatier J.-M., De Waard M., Hoshi T.;
RT "Mechanisms of maurotoxin action on Shaker potassium channels.";
RL Biophys. J. 79:776-787(2000).
RN [5]
RP DISULFIDE BONDS, AND MUTAGENESIS OF LYS-15 AND GLY-33.
RX PubMed=10970898; DOI=10.1074/jbc.m006810200;
RA Fajloun Z., Mosbah A., Carlier E., Mansuelle P., Sandoz G., Fathallah M.,
RA di Luccio E., Devaux C., Rochat H., Darbon H., De Waard M., Sabatier J.-M.;
RT "Maurotoxin versus Pi1/HsTx1 scorpion toxins. Toward new insights in the
RT understanding of their distinct disulfide bridge patterns.";
RL J. Biol. Chem. 275:39394-39402(2000).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LYS-23.
RX PubMed=10888198; DOI=10.1034/j.1399-3011.2000.00715.x;
RA Carlier E., Avdonin V., Geib S., Fajloun Z., Kharrat R., Rochat H.,
RA Sabatier J.-M., Hoshi T., De Waard M.;
RT "Effect of maurotoxin, a four disulfide-bridged toxin from the chactoid
RT scorpion Scorpio maurus, on Shaker K+ channels.";
RL J. Pept. Res. 55:419-427(2000).
RN [7]
RP FUNCTION.
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 [8]
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 [9]
RP FUNCTION, AND STRUCTURE BY NMR OF MAUROTOXIN-HSTX1 CHIMERA.
RX PubMed=15498765; DOI=10.1074/jbc.m410055200;
RA Regaya I., Beeton C., Ferrat G., Andreotti N., Darbon H., De Waard M.,
RA Sabatier J.M.;
RT "Evidence for domain-specific recognition of SK and Kv channels by MTX and
RT HsTx1 scorpion toxins.";
RL J. Biol. Chem. 279:55690-55696(2004).
RN [10]
RP FUNCTION.
RX PubMed=18042681; DOI=10.1110/ps.073122908;
RA Pimentel C., M'Barek S., Visan V., Grissmer S., Sampieri F., Sabatier J.M.,
RA Darbon H., Fajloun Z.;
RT "Chemical synthesis and 1H-NMR 3D structure determination of AgTx2-MTX
RT chimera, a new potential blocker for Kv1.2 channel, derived from MTX and
RT AgTx2 scorpion toxins.";
RL Protein Sci. 17:107-118(2008).
RN [11]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9365987;
RX DOI=10.1002/(sici)1097-0134(199711)29:3<321::aid-prot6>3.0.co;2-d;
RA Blanc E., Sabatier J.-M., Kharrat R., Meunier S., el Ayeb M.,
RA van Rietschoten J., Darbon H.;
RT "Solution structure of maurotoxin, a scorpion toxin from Scorpio maurus,
RT with high affinity for voltage-gated potassium channels.";
RL Proteins 29:321-333(1997).
RN [12]
RP STRUCTURE BY NMR.
RX PubMed=10631983; DOI=10.1110/ps.8.12.2672;
RA Savarin P., Romi-Lebrun R., Zinn-Justin S., Lebrun B., Nakajima T.,
RA Gilquin B., Menez A.;
RT "Structural and functional consequences of the presence of a fourth
RT disulfide bridge in the scorpion short toxins: solution structure of the
RT potassium channel inhibitor HsTX1.";
RL Protein Sci. 8:2672-2685(1999).
RN [13]
RP STRUCTURE BY NMR OF MAUROTOXIN-BUTANTOXIN CHIMERA.
RX PubMed=15971207; DOI=10.1002/prot.20509;
RA M'Barek S., Chagot B., Andreotti N., Visan V., Mansuelle P., Grissmer S.,
RA Marrakchi M., El Ayeb M., Sampieri F., Darbon H., Fajloun Z., De Waard M.,
RA Sabatier J.-M.;
RT "Increasing the molecular contacts between maurotoxin and Kv1.2 channel
RT augments ligand affinity.";
RL Proteins 60:401-411(2005).
CC -!- FUNCTION: Blocks voltage-gated potassium channels Kv1.2/KCNA2
CC (IC(50)=0.12-0.8 nM), KCa3.1/KCNN4 (IC(50)=1-2.2 nM), Shaker B
CC (IC(50)=2.39-80 nM), Kv1.1/KCNA1 (IC(50)=37-45 or no activity,
CC depending on the study), Kv1.3/KCNA3 (IC(50)=150-180 or no activity,
CC depending on the study). {ECO:0000269|PubMed:10888198,
CC ECO:0000269|PubMed:10920011, ECO:0000269|PubMed:12527813,
CC ECO:0000269|PubMed:15498765, ECO:0000269|PubMed:18042681,
CC ECO:0000269|PubMed:9022673, ECO:0000269|PubMed:9136903}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9022673}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9022673}.
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:9365987}.
CC -!- TOXIC DOSE: LD(50) is 4 ug/kg by intracerebroventricular injection into
CC mice. {ECO:0000269|PubMed:9022673, ECO:0000269|PubMed:9136903}.
CC -!- MISCELLANEOUS: Shows very weak or no activity on KCa1.1/KCNMA1,
CC KCa2.1/KCNN1, KCa2.2/KCNN2, KCa2.3/KCNN3, Kir2.3/KCNJ4.
CC {ECO:0000269|PubMed:10888198, ECO:0000269|PubMed:11527975,
CC ECO:0000269|PubMed:12527813}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 06 subfamily. {ECO:0000305}.
CC -!- CAUTION: Has not the same disulfide pairing as other members of alpha-
CC KTx 6. {ECO:0000305|PubMed:10970898, ECO:0000305|PubMed:9022673,
CC ECO:0000305|PubMed:9136903, ECO:0000305|PubMed:9365987,
CC ECO:0000305|PubMed:9792177}.
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DR PDB; 1TXM; NMR; -; A=1-34.
DR PDB; 1WPD; NMR; -; A=1-16.
DR PDB; 1WT7; NMR; -; A=3-34.
DR PDBsum; 1TXM; -.
DR PDBsum; 1WPD; -.
DR PDBsum; 1WT7; -.
DR AlphaFoldDB; P80719; -.
DR BMRB; P80719; -.
DR SMR; P80719; -.
DR EvolutionaryTrace; P80719; -.
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 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; 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;
KW Voltage-gated potassium channel impairing toxin.
FT PEPTIDE 1..34
FT /note="Potassium channel toxin alpha-KTx 6.2"
FT /id="PRO_0000044929"
FT SITE 23
FT /note="Basic residue of the functional dyad, critical for
FT activity"
FT /evidence="ECO:0000269|PubMed:10888198"
FT SITE 32
FT /note="Aromatic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT MOD_RES 34
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:9792177"
FT DISULFID 3..24
FT /evidence="ECO:0000269|PubMed:10970898,
FT ECO:0000269|PubMed:9022673, ECO:0000269|PubMed:9136903,
FT ECO:0000269|PubMed:9365987, ECO:0000269|PubMed:9792177,
FT ECO:0000312|PDB:1TXM"
FT DISULFID 9..29
FT /evidence="ECO:0000269|PubMed:10970898,
FT ECO:0000269|PubMed:9022673, ECO:0000269|PubMed:9136903,
FT ECO:0000269|PubMed:9365987, ECO:0000269|PubMed:9792177,
FT ECO:0000312|PDB:1TXM"
FT DISULFID 13..19
FT /evidence="ECO:0000269|PubMed:10970898,
FT ECO:0000269|PubMed:9022673, ECO:0000269|PubMed:9136903,
FT ECO:0000269|PubMed:9365987, ECO:0000269|PubMed:9792177,
FT ECO:0000312|PDB:1TXM"
FT DISULFID 31..34
FT /evidence="ECO:0000269|PubMed:10970898,
FT ECO:0000269|PubMed:9022673, ECO:0000269|PubMed:9136903,
FT ECO:0000269|PubMed:9365987, ECO:0000269|PubMed:9792177,
FT ECO:0000312|PDB:1TXM"
FT MUTAGEN 15
FT /note="K->Q: Induces a change in the third and fourth
FT disulfide bonds, leading to disulfide bonds between C-13
FT and C-31, and C-19 and C-34."
FT /evidence="ECO:0000269|PubMed:10970898"
FT MUTAGEN 23
FT /note="K->A: 1000-fold decrease in affinity for shaker B."
FT /evidence="ECO:0000269|PubMed:10888198"
FT MUTAGEN 33
FT /note="G->A: Induces a change in the third and fourth
FT disulfide bonds, leading to disulfide bonds between C-13
FT and C-31, and C-19 and C-34."
FT /evidence="ECO:0000269|PubMed:10970898"
FT HELIX 6..16
FT /evidence="ECO:0007829|PDB:1TXM"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:1WT7"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:1WT7"
SQ SEQUENCE 34 AA; 3621 MW; FB0BE07370536A48 CRC64;
VSCTGSKDCY APCRKQTGCP NAKCINKSCK CYGC
