KAX31_ANDMA
ID KAX31_ANDMA Reviewed; 38 AA.
AC P24662;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 2.
DT 25-MAY-2022, entry version 107.
DE RecName: Full=Potassium channel toxin alpha-KTx 3.1;
DE AltName: Full=Kaliotoxin {ECO:0000303|PubMed:1730708};
DE Short=KTX {ECO:0000303|PubMed:1730708};
DE AltName: Full=Kaliotoxin-1;
DE Short=KTX-1;
OS Androctonus mauritanicus mauritanicus (Scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Androctonus.
OX NCBI_TaxID=6860;
RN [1]
RP PROTEIN SEQUENCE OF 1-37, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=1730708; DOI=10.1016/s0021-9258(18)45993-5;
RA Crest M., Jacquet G., Gola M., Zerrouk H., Benslimane A., Rochat H.,
RA Mansuelle P., Martin-Eauclaire M.-F.;
RT "Kaliotoxin, a novel peptidyl inhibitor of neuronal BK-type Ca(2+)-
RT activated K+ channels characterized from Androctonus mauretanicus
RT mauretanicus venom.";
RL J. Biol. Chem. 267:1640-1647(1992).
RN [2]
RP FUNCTION, AND ACTIVITY PROFILE.
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 [3]
RP FUNCTION, AND ACTIVITY PROFILE.
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 [4]
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 [5]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=7524673; DOI=10.1021/bi00251a038;
RA Fernandez I., Romi R., Szendefi S., Martin-Eauclaire M.-F., Rochat H.,
RA van Rietschoten J., Pons M., Giralt E.;
RT "Kaliotoxin (1-37) shows structural differences with related potassium
RT channel blockers.";
RL Biochemistry 33:14256-14263(1994).
RN [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=9262650;
RX DOI=10.1002/(sici)1099-1387(199707)3:4<314::aid-psc117>3.0.co;2-e;
RA Gairi M., Romi R., Fernandez I., Rochat H., Martin-Eauclaire M.-F.,
RA van Rietschoten J., Pons M., Giralt E.;
RT "3D structure of kaliotoxin: is residue 34 a key for channel selectivity?";
RL J. Pept. Sci. 3:314-319(1997).
RN [7]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=15744789; DOI=10.1002/anie.200462516;
RA Lange A., Becker S., Seidel K., Giller K., Pongs O., Baldus M.;
RT "A concept for rapid protein-structure determination by solid-state NMR
RT spectroscopy.";
RL Angew. Chem. Int. Ed. 44:2089-2092(2005).
RN [8]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=16612389; DOI=10.1038/nature04649;
RA Lange A., Giller K., Hornig S., Martin-Eauclaire M.-F., Pongs O.,
RA Becker S., Baldus M.;
RT "Toxin-induced conformational changes in a potassium channel revealed by
RT solid-state NMR.";
RL Nature 440:959-962(2006).
CC -!- FUNCTION: Potent inhibitor voltage-gated potassium channels Kv1.3/KCNA3
CC (Kd=0.65 nM) and Kv1.1/KCNA1 (Kd=41 nM) (PubMed:7517498). It appears to
CC block channel activity by a simple bimolecular inhibition process.
CC Induces a transient period of fast flickering in the channel openings,
CC followed by an almost complete blockade of the channel. Its binding
CC affinity to rat brain synaptosomes is 5-fold higher than this of KTX-3.
CC Binding of the toxin to the channel is associated with significant
CC structural rearrangements in both molecules. It also shows a weak
CC interaction with nicotinic acetylcholine receptors (nAChR), suggesting
CC it may weakly inhibit it (PubMed:31276191).
CC {ECO:0000269|PubMed:1730708, ECO:0000269|PubMed:7517498}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1730708}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:1730708}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC -!- MISCELLANEOUS: Shows weak inhibition of large conductance calcium-
CC activated potassium channels (KCa1.1/KCNMA1) (Ki=1560 nM)
CC (PubMed:20007782). Shows weak or no inhibition on
CC Kv1.2/KCNA2(PubMed:7517498, PubMed:20007782). Shows no effect on
CC Kv1.5/KCNA5 and Kv3.1/KCNC1 (PubMed:7517498).
CC {ECO:0000269|PubMed:20007782, ECO:0000269|PubMed:7517498}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 03 subfamily. {ECO:0000305}.
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DR PIR; A42040; A42040.
DR PDB; 1KTX; NMR; -; A=1-37.
DR PDB; 1XSW; NMR; -; A=1-38.
DR PDB; 2KTX; NMR; -; A=1-38.
DR PDB; 2UVS; NMR; -; A=1-38.
DR PDB; 3ODV; X-ray; 0.95 A; A/B=1-38.
DR PDBsum; 1KTX; -.
DR PDBsum; 1XSW; -.
DR PDBsum; 2KTX; -.
DR PDBsum; 2UVS; -.
DR PDBsum; 3ODV; -.
DR AlphaFoldDB; P24662; -.
DR BMRB; P24662; -.
DR SMR; P24662; -.
DR EvolutionaryTrace; P24662; -.
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; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Secreted; Toxin; Voltage-gated potassium channel impairing toxin.
FT PEPTIDE 1..38
FT /note="Potassium channel toxin alpha-KTx 3.1"
FT /evidence="ECO:0000269|PubMed:1730708"
FT /id="PRO_0000044894"
FT REGION 26..33
FT /note="Interaction with Ca(2+)-activated K(+) channels"
FT /evidence="ECO:0000255"
FT DISULFID 8..28
FT /evidence="ECO:0000269|PubMed:15744789,
FT ECO:0000269|PubMed:16612389, ECO:0000269|PubMed:7524673,
FT ECO:0000269|PubMed:9262650"
FT DISULFID 14..33
FT /evidence="ECO:0000269|PubMed:15744789,
FT ECO:0000269|PubMed:16612389, ECO:0000269|PubMed:7524673,
FT ECO:0000269|PubMed:9262650"
FT DISULFID 18..35
FT /evidence="ECO:0000269|PubMed:15744789,
FT ECO:0000269|PubMed:16612389, ECO:0000269|PubMed:7524673,
FT ECO:0000269|PubMed:9262650"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:3ODV"
FT HELIX 11..14
FT /evidence="ECO:0007829|PDB:3ODV"
FT HELIX 15..20
FT /evidence="ECO:0007829|PDB:3ODV"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:3ODV"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:3ODV"
SQ SEQUENCE 38 AA; 4156 MW; E190050E4EA751A5 CRC64;
GVEINVKCSG SPQCLKPCKD AGMRFGKCMN RKCHCTPK
