KA153_ANDMA
ID KA153_ANDMA Reviewed; 37 AA.
AC P60208;
DT 16-JAN-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-JAN-2004, sequence version 1.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Potassium channel toxin alpha-KTx 15.3 {ECO:0000305};
DE AltName: Full=Toxin AmmTX3 {ECO:0000303|PubMed:12473099};
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, FUNCTION, MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND
RP PYROGLUTAMATE FORMATION AT GLN-1.
RC TISSUE=Venom;
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 [2]
RP MUTAGENESIS OF LYS-6; ARG-18 AND LYS-19.
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 [3]
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 [4]
RP FUNCTION, AND BIOASSAY.
RX PubMed=25356731; DOI=10.1097/fbp.0000000000000107;
RA Aidi-Knani S., Regaya I., Amalric M., Mourre C.;
RT "Kv4 channel blockade reduces motor and neuropsychiatric symptoms in rodent
RT models of Parkinson's disease.";
RL Behav. Pharmacol. 26:91-100(2015).
RN [5]
RP STRUCTURE BY NMR, DISULFIDE BOND, SYNTHESIS, AND FUNCTION.
RX PubMed=30529150; DOI=10.1016/j.bmc.2018.12.009;
RA Zoukimian C., Meudal H., De Waard S., Ouares K.A., Nicolas S., Canepari M.,
RA Beroud R., Landon C., De Waard M., Boturyn D.;
RT "Synthesis by native chemical ligation and characterization of the scorpion
RT toxin AmmTx3.";
RL Bioorg. Med. Chem. 27:247-253(2019).
CC -!- FUNCTION: Inhibits A-type (Kv4) voltage-gated potassium channels of
CC striated neurons (Ki=131 nM), probably by acting as a pore blocker
CC (PubMed:12473099, PubMed:23440961, PubMed:30529150). Has also been
CC shown to block ERG1/Kv11.1/KCNH2 potassium channels (IC(50)=7.9 uM)
CC (PubMed:18687312). The presence of the Kv4-associated proteins DPP6 or
CC DPP10 is mandatory to have high-affinity blockade of Kv4.2/KCND2 and
CC Kv4.3/KCND3 channels (80-90% inhibition at 500 nM of toxin)
CC (PubMed:23440961). In contrast, the presence of the Kv4-associated
CC protein KChIP1/KCNIP1 does not enhance the affinity blockade (only 40%
CC inhibition at 500 nM) (PubMed:23440961). In adult rat brain, the toxin
CC binds to sites in the striatum, and cerebellum. It shares the same
CC target in rat brain than AaTX1 (AC Q867F4) and BmTX3 (AC Q8I0L5). In
CC DPP6 knockout mice, A-type currents are about 20-fold less affected by
CC the toxin (PubMed:23440961). In rodent models of Parkinson's disease,
CC the toxin reduces motor symptoms and emotional and cognitive symptoms
CC (PubMed:25356731). {ECO:0000269|PubMed:12473099,
CC ECO:0000269|PubMed:18687312, ECO:0000269|PubMed:23440961,
CC ECO:0000269|PubMed:25356731, ECO:0000269|PubMed:30529150}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12473099}.
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:0000269|PubMed:30529150}.
CC -!- MASS SPECTROMETRY: Mass=3823.5; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:12473099};
CC -!- SIMILARITY: Belongs to the short scorpion toxin superfamily. Potassium
CC channel inhibitor family. Alpha-KTx 15 subfamily. {ECO:0000305}.
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DR PDB; 6GGZ; NMR; -; 1=2-37.
DR PDBsum; 6GGZ; -.
DR AlphaFoldDB; P60208; -.
DR BMRB; P60208; -.
DR SMR; P60208; -.
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; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Potassium channel impairing toxin;
KW Pyrrolidone carboxylic acid; Secreted; Toxin;
KW Voltage-gated potassium channel impairing toxin.
FT PEPTIDE 1..37
FT /note="Potassium channel toxin alpha-KTx 15.3"
FT /evidence="ECO:0000269|PubMed:12473099"
FT /id="PRO_0000044895"
FT SITE 6
FT /note="Hot spot residue in hERG blocking currents"
FT /evidence="ECO:0000305|PubMed:18687312"
FT SITE 18
FT /note="Hot spot basic residue in hERG blocking currents"
FT /evidence="ECO:0000305|PubMed:18687312"
FT SITE 19
FT /note="Hot spot basic residue in hERG blocking currents"
FT /evidence="ECO:0000305|PubMed:18687312"
FT SITE 27
FT /note="Basic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT SITE 36
FT /note="Aromatic residue of the functional dyad"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="Pyrrolidone carboxylic acid"
FT /evidence="ECO:0000269|PubMed:12473099"
FT DISULFID 8..28
FT /evidence="ECO:0000269|PubMed:30529150"
FT DISULFID 13..33
FT /evidence="ECO:0000269|PubMed:30529150"
FT DISULFID 17..35
FT /evidence="ECO:0000269|PubMed:30529150"
FT MUTAGEN 6
FT /note="K->V: Increase in hERG blocking activity with
FT activity close to BmTx3 activity (IC(50)=3.2 uM)."
FT /evidence="ECO:0000269|PubMed:18687312"
FT MUTAGEN 18
FT /note="R->A: Loss of hERG blocking activity."
FT /evidence="ECO:0000269|PubMed:18687312"
FT MUTAGEN 19
FT /note="K->A: Loss of hERG blocking activity."
FT /evidence="ECO:0000269|PubMed:18687312"
FT STRAND 2..7
FT /evidence="ECO:0007829|PDB:6GGZ"
FT HELIX 14..20
FT /evidence="ECO:0007829|PDB:6GGZ"
FT STRAND 26..29
FT /evidence="ECO:0007829|PDB:6GGZ"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:6GGZ"
SQ SEQUENCE 37 AA; 3846 MW; 29C076CEF36511C4 CRC64;
QIETNKKCQG GSCASVCRKV IGVAAGKCIN GRCVCYP
