KA152_MESMA
ID KA152_MESMA Reviewed; 59 AA.
AC Q8I0L5;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 77.
DE RecName: Full=Potassium channel toxin alpha-KTx 15.2 {ECO:0000305};
DE AltName: Full=BmTX3 {ECO:0000303|PubMed:11457451};
DE AltName: Full=BmTX3A {ECO:0000303|PubMed:14599291};
DE Flags: Precursor;
OS Mesobuthus martensii (Manchurian scorpion) (Buthus martensii).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida;
OC Scorpiones; Buthida; Buthoidea; Buthidae; Mesobuthus.
OX NCBI_TaxID=34649;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 23-59,
RP SYNTHESIS OF 23-59, FUNCTION, PYROGLUTAMATE FORMATION AT GLN-23, AND
RP 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=14599291; DOI=10.1042/bj20031324;
RA Huys I., Xu C.-Q., Wang C.-Z., Vacher H., Martin-Eauclaire M.-F.,
RA Chi C.-W., Tytgat J.;
RT "BmTx3, a scorpion toxin with two putative functional faces separately
RT active on A-type K+ and HERG currents.";
RL Biochem. J. 378:745-752(2004).
RN [2]
RP PROTEIN SEQUENCE OF 23-59, SYNTHESIS, FUNCTION, MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, AND PYROGLUTAMATE FORMATION AT GLN-23.
RC TISSUE=Venom;
RX PubMed=11457451; DOI=10.1016/s0014-5793(01)02620-5;
RA Vacher H., Romi-Lebrun R., Mourre C., Lebrun B., Kourrich S., Masmejean F.,
RA Nakajima T., Legros C., Crest M., Bougis P.E., Martin-Eauclaire M.-F.;
RT "A new class of scorpion toxin binding sites related to an A-type K+
RT channel: pharmacological characterization and localization in rat brain.";
RL FEBS Lett. 501:31-36(2001).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF 58-TYR-PRO-59.
RX PubMed=12473099; DOI=10.1046/j.1432-1033.2002.03294.x;
RA Vacher H., Alami M., Crest M., Possani L.D., Bougis P.E.,
RA Martin-Eauclaire M.-F.;
RT "Expanding the scorpion toxin alpha-KTX 15 family with AmmTX3 from
RT Androctonus mauretanicus.";
RL Eur. J. Biochem. 269:6037-6041(2002).
RN [4]
RP FUNCTION.
RX PubMed=16987219; DOI=10.1111/j.1460-9568.2006.05020.x;
RA Vacher H., Diochot S., Bougis P.E., Martin-Eauclaire M.F., Mourre C.;
RT "Kv4 channels sensitive to BmTX3 in rat nervous system: autoradiographic
RT analysis of their distribution during brain ontogenesis.";
RL Eur. J. Neurosci. 24:1325-1340(2006).
RN [5]
RP FUNCTION.
RX PubMed=23440961; DOI=10.1113/jphysiol.2012.248831;
RA Maffie J.K., Dvoretskova E., Bougis P.E., Martin-Eauclaire M.F., Rudy B.;
RT "Dipeptidyl-peptidase-like-proteins confer high sensitivity to the scorpion
RT toxin AmmTX3 to Kv4-mediated A-type K+ channels.";
RL J. Physiol. (Lond.) 591:2419-2427(2013).
RN [6]
RP STRUCTURE BY NMR OF 23-59, DISULFIDE BONDS, AND MUTAGENESIS OF
RP 58-TYR-PRO-59.
RX PubMed=12637022; DOI=10.1016/s1570-9639(02)00557-5;
RA Vacher H., Romi-Lebrun R., Crest M., Masmejean F., Bougis P.E., Darbon H.,
RA Martin-Eauclaire M.-F.;
RT "Functional consequences of deleting the two C-terminal residues of the
RT scorpion toxin BmTX3.";
RL Biochim. Biophys. Acta 1646:152-156(2003).
CC -!- FUNCTION: Blocks both human ERG1/Kv11.1/KCNH2 potassium channels (in a
CC reversible manner) (PubMed:14599291) and A-type voltage-gated potassium
CC channels Kv4/KCND (in an irreversible manner) (PubMed:11457451,
CC PubMed:12473099, PubMed:12637022). The presence of the Kv4-associated
CC proteins DPP6 or DPP10 is mandatory to have high-affinity blockade of
CC Kv4.2/KCND2 and Kv4.3/KCND3 channels (By similarity). In contrast, the
CC presence of the Kv4-associated protein KChIP1/KCNIP1 does not enhance
CC the affinity blockade (By similarity). May dispose of two functional
CC faces (A and B); the two basic residues (Arg-40 and Lys-41) on the
CC alpha-helix side of the peptide that blocks the hERG current (face A)
CC and the typical dyad through which it blocks A-type currents on the
CC beta-sheet side (face B) (PubMed:14599291). In adult rat brain, it
CC binds to sites in the striatum, hippocampus, superior colliculus, and
CC cerebellum. It shares the same target in rat brain than AaTX1 (AC
CC Q867F4) and AmmTX3 (AC P60208). In DPP6 knockout mice, A-type currents
CC are much less affected by the toxin than in wild-type mice
CC (PubMed:23440961). {ECO:0000250|UniProtKB:P60208,
CC ECO:0000269|PubMed:11457451, ECO:0000269|PubMed:12473099,
CC ECO:0000269|PubMed:14599291, ECO:0000269|PubMed:23440961}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11457451}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to a
CC beta-sheet by disulfide bonds (CSalpha/beta).
CC {ECO:0000250|UniProtKB:P84777}.
CC -!- MASS SPECTROMETRY: Mass=3751.8; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11457451};
CC -!- MISCELLANEOUS: Has no effect on Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3,
CC Kv7.1/KCNQ1, Kv7.1/KCNQ1+minK, and on Kir2.1/KCNJ2.
CC {ECO:0000269|PubMed:14599291}.
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 15 subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF541980; AAN34656.1; -; mRNA.
DR EMBL; AY156725; AAN85572.1; -; Genomic_DNA.
DR AlphaFoldDB; Q8I0L5; -.
DR SMR; Q8I0L5; -.
DR TCDB; 8.B.8.1.2; the Alpha-ktx15 scorpion toxin (Alpha-ktx15) family.
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 Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Potassium channel impairing toxin; Pyrrolidone carboxylic acid;
KW Secreted; Signal; Toxin; Voltage-gated potassium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:11457451,
FT ECO:0000269|PubMed:14599291"
FT CHAIN 23..59
FT /note="Potassium channel toxin alpha-KTx 15.2"
FT /evidence="ECO:0000269|PubMed:11457451,
FT ECO:0000269|PubMed:14599291"
FT /id="PRO_0000035319"
FT SITE 28
FT /note="Hot spot residue in hERG blocking currents"
FT /evidence="ECO:0000305|PubMed:14599291"
FT SITE 40
FT /note="Hot spot basic residue in hERG blocking currents"
FT /evidence="ECO:0000305|PubMed:14599291"
FT SITE 41
FT /note="Hot spot basic residue in hERG blocking currents"
FT /evidence="ECO:0000305|PubMed:14599291"
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:11457451,
FT ECO:0000269|PubMed:14599291"
FT DISULFID 30..50
FT /evidence="ECO:0000269|PubMed:12637022"
FT DISULFID 35..55
FT /evidence="ECO:0000269|PubMed:12637022"
FT DISULFID 39..57
FT /evidence="ECO:0000269|PubMed:12637022"
FT MUTAGEN 58..59
FT /note="Missing: Decrease in blocking of A-type voltage-
FT gated potassium channels, loss of inhibition of Kv4.1/KCND1
FT and Kv4.3/KCND3."
FT /evidence="ECO:0000269|PubMed:12637022,
FT ECO:0000269|PubMed:16987219"
SQ SEQUENCE 59 AA; 6206 MW; 4A3D46C865996652 CRC64;
MKFSSIILLT LLICSMSKFG NCQVETNVKC QGGSCASVCR KAIGVAAGKC INGRCVCYP
