KAX61_PANIM
ID KAX61_PANIM Reviewed; 35 AA.
AC Q10726;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 25-MAY-2022, entry version 106.
DE RecName: Full=Potassium channel toxin alpha-KTx 6.1;
DE AltName: Full=PiTX-K-gamma {ECO:0000303|PubMed:8913348};
DE AltName: Full=Potassium channel-blocking toxin 1;
DE Short=Pi-1;
DE Short=Pi1 {ECO:0000303|PubMed:8645186, ECO:0000303|PubMed:9001397};
OS Pandinus imperator (Emperor scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Iurida; Scorpionoidea; Scorpionidae; Pandininae; Pandinus.
OX NCBI_TaxID=55084;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, DISULFIDE BONDS, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8645186; DOI=10.1042/bj3150977;
RA Olamendi-Portugal T., Gomez-Lagunas F., Gurrola G.B., Possani L.D.;
RT "A novel structural class of K+-channel blocking toxin from the scorpion
RT Pandinus imperator.";
RL Biochem. J. 315:977-981(1996).
RN [2]
RP PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8913348;
RA Rogowski R.S., Collins J.H., O'Neill T.J., Gustafson T.A., Werkman T.R.,
RA Rogawski M.A., Tenenholz T.C., Weber D.J., Blaustein M.P.;
RT "Three new toxins from the scorpion Pandinus imperator selectively block
RT certain voltage-gated K+ channels.";
RL Mol. Pharmacol. 50:1167-1177(1996).
RN [3]
RP FUNCTION.
RX PubMed=9001397; DOI=10.1016/s0014-5793(96)01387-7;
RA Gomez-Lagunas F., Olamendi-Portugal T., Possani L.D.;
RT "Block of ShakerB K+ channels by Pi1, a novel class of scorpion toxin.";
RL FEBS Lett. 400:197-200(1997).
RN [4]
RP FUNCTION.
RX PubMed=9464266; DOI=10.1006/bbrc.1997.8018;
RA Peter M. Jr., Varga Z., Panyi G., Bene L., Damjanovich S., Pieri C.,
RA Possani L.D., Gaspar R. Jr.;
RT "Pandinus imperator scorpion venom blocks voltage-gated K+ channels in
RT human lymphocytes.";
RL Biochem. Biophys. Res. Commun. 242:621-625(1998).
RN [5]
RP FUNCTION, TOXIC DOSE, AND SYNTHESIS.
RX PubMed=10931199; DOI=10.1046/j.1432-1327.2000.01577.x;
RA Fajloun Z., Carlier E., Lecomte C., Geib S., Di Luccio E., Bichet D.,
RA Mabrouk K., Rochat H., De Waard M., Sabatier J.M.;
RT "Chemical synthesis and characterization of Pi1, a scorpion toxin from
RT Pandinus imperator active on K+ channels.";
RL Eur. J. Biochem. 267:5149-5155(2000).
RN [6]
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 [7]
RP MUTAGENESIS OF ARG-5; ARG-12; LYS-24; LYS-31 AND TYR-33, AND SITES.
RX PubMed=12962541; DOI=10.1042/bj20030115;
RA Mouhat S., Mosbah A., Visan V., Wulff H., Delepierre M., Darbon H.,
RA Grissmer S., De Waard M., Sabatier J.M.;
RT "The 'functional' dyad of scorpion toxin Pi1 is not itself a prerequisite
RT for toxin binding to the voltage-gated Kv1.2 potassium channels.";
RL Biochem. J. 377:25-36(2004).
RN [8]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9054572; DOI=10.1021/bi9617116;
RA Delepierre M., Prochnicka-Chalufour A., Possani L.D.;
RT "A novel potassium channel blocking toxin from the scorpion Pandinus
RT imperator: a 1H NMR analysis using a nano-NMR probe.";
RL Biochemistry 36:2649-2658(1997).
RN [9]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=16247791; DOI=10.1002/prot.20681;
RA Carrega L., Mosbah A., Ferrat G., Beeton C., Andreotti N., Mansuelle P.,
RA Darbon H., De Waard M., Sabatier J.M.;
RT "The impact of the fourth disulfide bridge in scorpion toxins of the alpha-
RT KTx6 subfamily.";
RL Proteins 61:1010-1023(2005).
CC -!- FUNCTION: Potently and reversibly inhibits the insect voltage-gated
CC Shaker (Sh) potassium channel (isoform alpha (B)), the mammalian
CC voltage-gated potassium channels Kv1.2/KCNA2 (IC(50)=0.44 nM), and the
CC calcium-activated potassium channel KCa2.3/KCNN3 (Kd=330 nM)
CC (PubMed:9001397, PubMed:10931199, PubMed:11527975). Its effect on
CC Kv1.3/KCNA3 is controversial, since this channel is voltage-
CC independently inhibited in PubMed:9464266, but is not affected in
CC PubMed:10931199. Furthermore, this toxin competes with apamin (a small
CC conductance calcium-activated potassium channel inhibitor) for binding
CC to rat brain synaptosomes. {ECO:0000269|PubMed:10931199,
CC ECO:0000269|PubMed:11527975, ECO:0000269|PubMed:8645186,
CC ECO:0000269|PubMed:9001397, ECO:0000269|PubMed:9464266}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8645186,
CC ECO:0000269|PubMed:8913348}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8645186, ECO:0000305|PubMed:8913348}.
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:16247791}.
CC -!- DOMAIN: The alpha-helical domain may play a key role in the recognition
CC of SK channels.
CC -!- DOMAIN: The beta-sheet structure may be involved in bioactivity on Kv
CC channels.
CC -!- TOXIC DOSE: LD(50) is 10 ug/kg by intraperitoneal injection into mice.
CC {ECO:0000269|PubMed:10931199}.
CC -!- MISCELLANEOUS: Pi1 analog that is synthesized with a phosphorylation at
CC Tyr-33 (P-Pi1) suffers a 200-fold decrease in LD(50), a 200-fold
CC decrease of potency in competition assay with apamin, and a 58-fold
CC decrease in inhibiting Kv1.2/KCNA2 channels.
CC -!- MISCELLANEOUS: Does not or very weakly inhibits KCa2.2/KCNN2 (Kd> 1 uM)
CC and Kv1.1/KCNA1 (no effect observed at 5 uM).
CC {ECO:0000269|PubMed:10931199, ECO:0000269|PubMed:8913348}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 06 subfamily. {ECO:0000305}.
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DR PIR; S69599; S69599.
DR PDB; 1WZ5; NMR; -; A=1-35.
DR PDBsum; 1WZ5; -.
DR AlphaFoldDB; Q10726; -.
DR SMR; Q10726; -.
DR EvolutionaryTrace; Q10726; -.
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 SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS01138; SCORP_SHORT_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 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..35
FT /note="Potassium channel toxin alpha-KTx 6.1"
FT /evidence="ECO:0000269|PubMed:8645186,
FT ECO:0000269|PubMed:8913348"
FT /id="PRO_0000044912"
FT SITE 5
FT /note="Part of the basic ring which may anchor to the
FT external vestibule of the K(+) channel"
FT /evidence="ECO:0000269|PubMed:12962541"
FT SITE 12
FT /note="Part of the basic ring which may anchor to the
FT external vestibule of the K(+) channel"
FT /evidence="ECO:0000269|PubMed:12962541"
FT SITE 24
FT /note="Basic residue of the functional dyad"
FT /evidence="ECO:0000269|PubMed:12962541"
FT SITE 28
FT /note="Part of the basic ring which may anchor to the
FT external vestibule of the K(+) channel"
FT /evidence="ECO:0000305|PubMed:12962541"
FT SITE 31
FT /note="Part of the basic ring which may anchor to the
FT external vestibule of the K(+) channel"
FT /evidence="ECO:0000269|PubMed:12962541"
FT SITE 33
FT /note="Aromatic residue of the functional dyad"
FT /evidence="ECO:0000269|PubMed:12962541"
FT DISULFID 4..25
FT /evidence="ECO:0000269|PubMed:16247791,
FT ECO:0000269|PubMed:8645186, ECO:0000269|PubMed:9054572,
FT ECO:0000312|PDB:1WZ5"
FT DISULFID 10..30
FT /evidence="ECO:0000269|PubMed:16247791,
FT ECO:0000269|PubMed:8645186, ECO:0000269|PubMed:9054572,
FT ECO:0000312|PDB:1WZ5"
FT DISULFID 14..32
FT /evidence="ECO:0000269|PubMed:16247791,
FT ECO:0000269|PubMed:8645186, ECO:0000269|PubMed:9054572,
FT ECO:0000312|PDB:1WZ5"
FT DISULFID 20..35
FT /evidence="ECO:0000269|PubMed:16247791,
FT ECO:0000269|PubMed:8645186, ECO:0000269|PubMed:9054572,
FT ECO:0000312|PDB:1WZ5"
FT MUTAGEN 5
FT /note="R->A: 51-fold decrease in inhibiting Kv1.2/KCNA2
FT channels; when associated with A-12. 479-fold decrease in
FT inhibiting Kv1.2/KCNA2 channels; when associated with A-
FT 31."
FT /evidence="ECO:0000269|PubMed:12962541"
FT MUTAGEN 12
FT /note="R->A: 51-fold decrease in inhibiting Kv1.2/KCNA2
FT channels; when associated with A-5."
FT /evidence="ECO:0000269|PubMed:12962541"
FT MUTAGEN 24
FT /note="K->A: 500-fold decrease in LD(50), 600-fold decrease
FT of potency in competition assay with apamin, and 17000-fold
FT decrease in inhibiting Kv1.2/KCNA2 channels; when
FT associated with A-33."
FT /evidence="ECO:0000269|PubMed:12962541"
FT MUTAGEN 31
FT /note="K->A: 294-fold decrease in inhibiting Kv1.2/KCNA2
FT channels. 479-fold decrease in inhibiting Kv1.2/KCNA2
FT channels; when associated with A-5."
FT /evidence="ECO:0000269|PubMed:12962541"
FT MUTAGEN 33
FT /note="Y->A: 500-fold decrease in LD(50), 600-fold decrease
FT of potency in competition assay with apamin, and 17,000-
FT fold decrease in inhibiting Kv1.2/KCNA2 channels; when
FT associated with A-24."
FT /evidence="ECO:0000269|PubMed:12962541"
FT TURN 6..10
FT /evidence="ECO:0007829|PDB:1WZ5"
FT HELIX 11..17
FT /evidence="ECO:0007829|PDB:1WZ5"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:1WZ5"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:1WZ5"
SQ SEQUENCE 35 AA; 3843 MW; 208001C82B2C9800 CRC64;
LVKCRGTSDC GRPCQQQTGC PNSKCINRMC KCYGC
