KAX42_TITSE
ID KAX42_TITSE Reviewed; 57 AA.
AC P56219; A0A7S8MU87;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 09-SEP-2003, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Potassium channel toxin alpha-KTx 4.2;
DE AltName: Full=Neurotoxin Ts-kappa {ECO:0000303|PubMed:8706835};
DE Short=TsK {ECO:0000303|PubMed:8706835};
DE Short=TsKappa {ECO:0000303|PubMed:11527975, ECO:0000303|PubMed:18687312, ECO:0000303|PubMed:8706835};
DE AltName: Full=Tityustoxin-9 {ECO:0000305};
DE Short=Ts9 {ECO:0000303|PubMed:19689419};
DE Flags: Precursor;
OS Tityus serrulatus (Brazilian scorpion).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Tityus.
OX NCBI_TaxID=6887;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 23-57, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=8706835; DOI=10.1016/0014-5793(96)00616-3;
RA Legros C., Oughideni R., Darbon H., Rochat H., Bougis P.E.,
RA Martin-Eauclaire M.-F.;
RT "Characterization of a new peptide from Tityus serrulatus scorpion venom
RT which is a ligand of the apamin-binding site.";
RL FEBS Lett. 390:81-84(1996).
RN [2] {ECO:0000312|EMBL:QPD99048.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Telson;
RX PubMed=33181162; DOI=10.1016/j.toxicon.2020.11.001;
RA Kalapothakis Y., Miranda K., Pereira A.H., Witt A.S.A., Marani C.,
RA Martins A.P., Leal H.G., Campos-Junior E., Pimenta A.M.C., Borges A.,
RA Chavez-Olortegui C., Kalapothakis E.;
RT "Novel components of Tityus serrulatus venom: a transcriptomic approach.";
RL Toxicon 189:91-104(2021).
RN [3]
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 [4]
RP FUNCTION.
RX PubMed=18687312; DOI=10.1016/j.bcp.2008.07.008;
RA Abdel-Mottaleb Y., Corzo G., Martin-Eauclaire M.F., Satake H., Ceard B.,
RA Peigneur S., Nambaru P., Bougis P.E., Possani L.D., Tytgat J.;
RT "A common 'hot spot' confers hERG blockade activity to alpha-scorpion
RT toxins affecting K+ channels.";
RL Biochem. Pharmacol. 76:805-815(2008).
RN [5]
RP NOMENCLATURE.
RX PubMed=19689419; DOI=10.2174/092986609788923329;
RA Cologna C.T., Marcussi S., Giglio J.R., Soares A.M., Arantes E.C.;
RT "Tityus serrulatus scorpion venom and toxins: an overview.";
RL Protein Pept. Lett. 16:920-932(2009).
RN [6]
RP STRUCTURE BY NMR OF 23-57, DISULFIDE BONDS, AND FUNCTION.
RX PubMed=9365990;
RX DOI=10.1002/(sici)1097-0134(199711)29:3<359::aid-prot9>3.0.co;2-5;
RA Blanc E., Lecomte C., Martin-Eauclaire M.-F., van Rietschoten J.,
RA Sabatier J.-M., Darbon H.;
RT "Solution structure of TsKappa, a charybdotoxin-like scorpion toxin from
RT Tityus serrulatus with high affinity for apamin-sensitive Ca(2+)-activated
RT K+ channels.";
RL Proteins 29:359-369(1997).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 23-57, SYNTHESIS OF 23-57, AND
RP DISULFIDE BONDS.
RX PubMed=29483648; DOI=10.1038/s41594-018-0033-9;
RA Correnti C.E., Gewe M.M., Mehlin C., Bandaranayake A.D., Johnsen W.A.,
RA Rupert P.B., Brusniak M.Y., Clarke M., Burke S.E., De Van Der Schueren W.,
RA Pilat K., Turnbaugh S.M., May D., Watson A., Chan M.K., Bahl C.D.,
RA Olson J.M., Strong R.K.;
RT "Screening, large-scale production and structure-based classification of
RT cystine-dense peptides.";
RL Nat. Struct. Mol. Biol. 25:270-278(2018).
CC -!- FUNCTION: Blocker for small-conductance calcium-activated potassium
CC channels KCa2.2/KCNN2 (Kd=80 nM) and KCa2.3/KCNN3 (Kd=197 nM)
CC (PubMed:11527975) and ERG1/Kv11.1/KCNH2 potassium channels (53%
CC inhibition at 5 uM) (PubMed:18687312). Has also been shown to inhibit
CC Kv1.1/KCNA1 and Nav1.7/SCN9A with a moderate potency, as well as
CC Kv11.1/KCNH2/ERG1 and Kv1.2/KCNA2 with a low potency (PubMed:29483648).
CC {ECO:0000269|PubMed:11527975, ECO:0000269|PubMed:18687312,
CC ECO:0000269|PubMed:29483648}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8706835}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8706835}.
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:9365990}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 04 subfamily. {ECO:0000305}.
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DR EMBL; MT450712; QPD99048.1; -; mRNA.
DR PIR; S70473; S70473.
DR PDB; 1TSK; NMR; -; A=23-57.
DR PDB; 6ATL; X-ray; 1.80 A; A/C=23-57.
DR PDBsum; 1TSK; -.
DR PDBsum; 6ATL; -.
DR AlphaFoldDB; P56219; -.
DR SMR; P56219; -.
DR EvolutionaryTrace; P56219; -.
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:0017080; F:sodium 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; Signal; Toxin;
KW Voltage-gated potassium channel impairing toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..22
FT /note="Removed by a carboxypeptidase"
FT /evidence="ECO:0000269|PubMed:8706835"
FT /id="PRO_0000035329"
FT CHAIN 23..57
FT /note="Potassium channel toxin alpha-KTx 4.2"
FT /evidence="ECO:0000269|PubMed:8706835"
FT /id="PRO_0000035330"
FT DISULFID 29..50
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:9365990, ECO:0000312|PDB:1TSK,
FT ECO:0000312|PDB:6ATL"
FT DISULFID 35..55
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:9365990, ECO:0000312|PDB:1TSK,
FT ECO:0000312|PDB:6ATL"
FT DISULFID 39..57
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:9365990, ECO:0000312|PDB:1TSK,
FT ECO:0000312|PDB:6ATL"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:6ATL"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:6ATL"
FT HELIX 36..39
FT /evidence="ECO:0007829|PDB:6ATL"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:1TSK"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:6ATL"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:6ATL"
SQ SEQUENCE 57 AA; 6392 MW; 044A29EDE4512A18 CRC64;
MKVLYGILII FILCSMFYLS QEVVIGQRCY RSPDCYSACK KLVGKATGKC TNGRCDC
