SCM1_MESMA
ID SCM1_MESMA Reviewed; 84 AA.
AC P45697;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Alpha-like toxin BmK M1 {ECO:0000303|PubMed:10089445, ECO:0000303|PubMed:10493862, ECO:0000303|PubMed:11322948, ECO:0000303|PubMed:12692120, ECO:0000303|PubMed:12705833, ECO:0000303|PubMed:15321715, ECO:0000303|PubMed:9248001};
DE Short=BmK-M1;
DE Short=BmKM1;
DE AltName: Full=BmK-I;
DE Short=BmK I {ECO:0000303|PubMed:14554105, ECO:0000303|PubMed:16229835, ECO:0000303|PubMed:19162162, ECO:0000303|PubMed:20678086, ECO:0000303|PubMed:8896191};
DE Short=BmKI;
DE AltName: Full=BmK1;
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].
RC TISSUE=Venom gland;
RX PubMed=9248001; DOI=10.1016/s0041-0101(96)00224-3;
RA Xiong Y.-M., Ling M.-H., Wang D.-C., Chi C.-W.;
RT "The cDNA and genomic DNA sequences of a mammalian neurotoxin from the
RT scorpion Buthus martensii Karsch.";
RL Toxicon 35:1025-1031(1997).
RN [2]
RP PROTEIN SEQUENCE OF 20-83, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=8896191; DOI=10.1016/0041-0101(96)00065-7;
RA Ji Y.-H., Mansuelle P., Terakawa S., Kopeyan C., Yanaihara N., Hsu K.,
RA Rochat H.;
RT "Two neurotoxins (BmK I and BmK II) from the venom of the scorpion Buthus
RT martensi Karsch: purification, amino acid sequences and assessment of
RT specific activity.";
RL Toxicon 34:987-1001(1996).
RN [3]
RP FUNCTION, AND FUNCTION ON SCN5A SODIUM CHANNELS.
RX PubMed=11322948; DOI=10.1016/s0014-5793(01)02365-1;
RA Goudet C., Huys I., Clynen E., Schoofs L., Wang D.C., Waelkens E.,
RA Tytgat J.;
RT "Electrophysiological characterization of BmK M1, an alpha-like toxin from
RT Buthus martensi Karsch venom.";
RL FEBS Lett. 495:61-65(2001).
RN [4]
RP MUTAGENESIS OF TYR-24; LYS-27; PRO-28; HIS-29; ASN-30; TYR-40; LYS-47;
RP ASP-72; ARG-77; LYS-81 AND HIS-83, FUNCTION ON SCN2A AND SCN4A SODIUM
RP CHANNELS, AND TOXIC DOSE.
RX PubMed=12705833; DOI=10.1021/bi0270438;
RA Wang C.-G., Gilles N., Hamon A., Le Gall F., Stankiewicz M., Pelhate M.,
RA Xiong Y.-M., Wang D.-C., Chi C.-W.;
RT "Exploration of the functional site of a scorpion alpha-like toxin by site-
RT directed mutagenesis.";
RL Biochemistry 42:4699-4708(2003).
RN [5]
RP MUTAGENESIS OF TYR-24; TRP-57 AND TYR-61.
RX PubMed=12692120; DOI=10.1074/jbc.m211931200;
RA Sun Y.-M., Bosmans F., Zhu R.-H., Goudet C., Xiong Y.-M., Tytgat J.,
RA Wang D.-C.;
RT "Importance of the conserved aromatic residues in the scorpion alpha-like
RT toxin BmK M1: the hydrophobic surface region revisited.";
RL J. Biol. Chem. 278:24125-24131(2003).
RN [6]
RP FUNCTION, AND BIOASSAY.
RX PubMed=14554105; DOI=10.1016/s0041-008x(03)00260-6;
RA Bai Z.T., Zhang X.Y., Ji Y.H.;
RT "Fos expression in rat spinal cord induced by peripheral injection of BmK
RT I, an alpha-like scorpion neurotoxin.";
RL Toxicol. Appl. Pharmacol. 192:78-85(2003).
RN [7]
RP FUNCTION, TOXIC DOSE, AND MUTAGENESIS OF VAL-20; ARG-21; ASP-22; ILE-25;
RP PRO-28; HIS-29; GLY-53; GLY-62; LEU-70; PRO-71; ILE-76; VAL-78; PRO-79 AND
RP GLY-80.
RX PubMed=15677695; DOI=10.1096/fj.04-3171com;
RA Liu L.-H., Bosmans F., Maertens C., Zhu R.-H., Wang D.-C., Tytgat J.;
RT "Molecular basis of the mammalian potency of the scorpion alpha-like toxin,
RT BmK M1.";
RL FASEB J. 19:594-596(2005).
RN [8]
RP FUNCTION, AND BIOASSAY.
RX PubMed=16229835; DOI=10.1016/j.expneurol.2005.09.006;
RA Bai Z.T., Zhao R., Zhang X.Y., Chen J., Liu T., Ji Y.H.;
RT "The epileptic seizures induced by BmK I, a modulator of sodium channels.";
RL Exp. Neurol. 197:167-176(2006).
RN [9]
RP FUNCTION.
RX PubMed=19162162; DOI=10.1016/j.tiv.2008.12.022;
RA Zhu M.M., Tan M., Cheng H.W., Ji Y.H.;
RT "The alpha-like scorpion toxin BmK I enhances membrane excitability via
RT persistent sodium current by preventing slow inactivation and deactivation
RT of rNav1.2a expressed in Xenopus oocytes.";
RL Toxicol. in Vitro 23:561-568(2009).
RN [10]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=20678086; DOI=10.1042/bj20100517;
RA He H., Liu Z., Dong B., Zhou J., Zhu H., Ji Y.;
RT "Molecular determination of selectivity of the site 3 modulator (BmK I) to
RT sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-
RT induced neuronal hyperexcitability.";
RL Biochem. J. 431:289-298(2010).
RN [11]
RP CRYSTALLIZATION.
RC TISSUE=Venom;
RX PubMed=10089445; DOI=10.1107/s0907444998006593;
RA Li H.-M., Zhao T., Jin L., Wang M., Zhang Y., Wang D.-C.;
RT "A series of bioactivity-variant neurotoxins from scorpion Buthus martensii
RT Karsch: purification, crystallization and crystallographic analysis.";
RL Acta Crystallogr. D 55:341-344(1999).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 20-83.
RX PubMed=10493862; DOI=10.1006/jmbi.1999.3036;
RA He X.-L., Li H.-M., Zeng Z.-H., Liu X.-Q., Wang M., Wang D.-C.;
RT "Crystal structures of two alpha-like scorpion toxins: non-proline cis
RT peptide bonds and implications for new binding site selectivity on the
RT sodium channel.";
RL J. Mol. Biol. 292:125-135(1999).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 19-83, AND MUTAGENESIS OF LYS-27
RP AND PRO-28.
RX PubMed=15321715; DOI=10.1016/j.jmb.2004.06.067;
RA Guan R.-J., Xiang Y., He X.-L., Wang C.-G., Wang M., Zhang Y.,
RA Sundberg E.J., Wang D.-C.;
RT "Structural mechanism governing cis and trans isomeric states and an
RT intramolecular switch for cis/trans isomerization of a non-proline peptide
RT bond observed in crystal structures of scorpion toxins.";
RL J. Mol. Biol. 341:1189-1204(2004).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 19-83, AND MUTAGENESIS.
RX PubMed=16209876; DOI=10.1016/j.jmb.2005.08.068;
RA Ye X., Bosmans F., Li C., Zhang Y., Wang D.-C., Tytgat J.;
RT "Structural basis for the voltage-gated Na+ channel selectivity of the
RT scorpion alpha-like toxin BmK M1.";
RL J. Mol. Biol. 353:788-803(2005).
CC -!- FUNCTION: Alpha toxins bind voltage-independently at site-3 of sodium
CC channels (Nav) and inhibit the inactivation of the activated channels
CC thereby blocking neuronal transmission. This toxin is active against
CC both mammals and insects, and is classified as an alpha-like toxin. It
CC is active on Nav1.2/SCN2A (EC(50)=139-252 nM), Nav1.3/SCN3A (EC(50)=565
CC nM), Nav1.4/SCN4A and Nav1.5/SCN5A (EC(50)=195-500 nM), Nav1.6/SCN8A
CC (EC(50)=214 nM), and drosophila DmNav1 (EC(50)=30 nM) (PubMed:11322948,
CC PubMed:12705833, PubMed:15677695, PubMed:19162162, PubMed:20678086). In
CC mNav1.6/SCN8A, the toxin induces a large increase in both transient and
CC persistent currents, which correlates with a prominent reduction in the
CC fast component of inactivating current (PubMed:20678086). In
CC rNav1.2/SCN2A and rNav1.3/SCN3A, toxin-increased currents is much
CC smaller (PubMed:19162162, PubMed:20678086). Moreover, the toxin only
CC accelerates the slow inactivation development and delay recovery of
CC mNav1.6/SCN8A through binding to the channel in the open state
CC (PubMed:20678086). Is 6-fold more toxic than BmK-M2. In vivo,
CC intrahippocampal injection into rat induces epileptiform responses
CC (PubMed:16229835). In addition, intraplantar injection into rat induces
CC spontaneous nociception and hyperalgesia (PubMed:14554105).
CC {ECO:0000269|PubMed:11322948, ECO:0000269|PubMed:12705833,
CC ECO:0000269|PubMed:14554105, ECO:0000269|PubMed:15677695,
CC ECO:0000269|PubMed:16229835, ECO:0000269|PubMed:19162162,
CC ECO:0000269|PubMed:20678086}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8896191}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:8896191}.
CC -!- DOMAIN: Has the structural arrangement of an alpha-helix connected to
CC antiparallel beta-sheets by disulfide bonds (CS-alpha/beta).
CC {ECO:0000269|PubMed:10493862, ECO:0000269|PubMed:15321715,
CC ECO:0000269|PubMed:16209876}.
CC -!- TOXIC DOSE: LD(50) is 0.75 mg/kg by intravenous injection into mice.
CC {ECO:0000269|PubMed:12705833}.
CC -!- TOXIC DOSE: LD(50) is 0.53 mg/kg by intravenous injection into tail
CC mice. {ECO:0000269|PubMed:12705833, ECO:0000269|PubMed:15677695}.
CC -!- MISCELLANEOUS: Exists in two forms, due to cis-trans isomerization at
CC 28-Pro-His-29. {ECO:0000269|PubMed:15321715}.
CC -!- MISCELLANEOUS: Has insignificant effect on Nav1.2/SCN2A.
CC {ECO:0000269|PubMed:12705833, ECO:0000269|PubMed:15677695}.
CC -!- SIMILARITY: Belongs to the long (4 C-C) scorpion toxin superfamily.
CC Sodium channel inhibitor family. Alpha subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA69557.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF057554; AAC13693.1; -; Genomic_DNA.
DR EMBL; U28659; AAA69557.1; ALT_INIT; mRNA.
DR PDB; 1DJT; X-ray; 1.20 A; A/B=20-83.
DR PDB; 1SN1; X-ray; 1.70 A; A=20-83.
DR PDB; 1T7A; X-ray; 1.50 A; A=20-83.
DR PDB; 1T7B; X-ray; 1.85 A; A=20-83.
DR PDB; 1T7E; X-ray; 1.40 A; A=20-83.
DR PDB; 1ZU3; X-ray; 1.33 A; A=20-83.
DR PDB; 1ZUT; X-ray; 1.70 A; A=20-83.
DR PDB; 1ZVE; X-ray; 1.70 A; A=20-83.
DR PDB; 1ZVG; X-ray; 1.20 A; A=20-83.
DR PDB; 1ZYV; X-ray; 1.50 A; A=20-83.
DR PDB; 1ZYW; X-ray; 1.30 A; A=20-83.
DR PDBsum; 1DJT; -.
DR PDBsum; 1SN1; -.
DR PDBsum; 1T7A; -.
DR PDBsum; 1T7B; -.
DR PDBsum; 1T7E; -.
DR PDBsum; 1ZU3; -.
DR PDBsum; 1ZUT; -.
DR PDBsum; 1ZVE; -.
DR PDBsum; 1ZVG; -.
DR PDBsum; 1ZYV; -.
DR PDBsum; 1ZYW; -.
DR AlphaFoldDB; P45697; -.
DR SMR; P45697; -.
DR TCDB; 8.B.1.1.1; the long (4c-c) scorpion toxin (l-st) superfamily.
DR EvolutionaryTrace; P45697; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006952; P:defense response; IEA:InterPro.
DR CDD; cd00107; Knot1; 1.
DR Gene3D; 3.30.30.10; -; 1.
DR InterPro; IPR044062; LCN-type_CS_alpha_beta_dom.
DR InterPro; IPR003614; Scorpion_toxin-like.
DR InterPro; IPR036574; Scorpion_toxin-like_sf.
DR InterPro; IPR018218; Scorpion_toxinL.
DR InterPro; IPR002061; Scorpion_toxinL/defensin.
DR Pfam; PF00537; Toxin_3; 1.
DR PRINTS; PR00285; SCORPNTOXIN.
DR SMART; SM00505; Knot1; 1.
DR SUPFAM; SSF57095; SSF57095; 1.
DR PROSITE; PS51863; LCN_CSAB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cardiotoxin; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:8896191"
FT CHAIN 20..83
FT /note="Alpha-like toxin BmK M1"
FT /evidence="ECO:0000269|PubMed:8896191"
FT /id="PRO_0000035236"
FT PROPEP 84
FT /note="Removed by a carboxypeptidase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000035237"
FT DOMAIN 21..83
FT /note="LCN-type CS-alpha/beta"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01210"
FT DISULFID 31..82
FT /evidence="ECO:0000269|PubMed:10493862,
FT ECO:0000269|PubMed:15321715, ECO:0000269|PubMed:16209876,
FT ECO:0000312|PDB:1DJT, ECO:0000312|PDB:1SN1,
FT ECO:0000312|PDB:1T7A, ECO:0000312|PDB:1T7B,
FT ECO:0000312|PDB:1T7E, ECO:0000312|PDB:1ZU3,
FT ECO:0000312|PDB:1ZUT, ECO:0000312|PDB:1ZVE,
FT ECO:0000312|PDB:1ZVG, ECO:0000312|PDB:1ZYV,
FT ECO:0000312|PDB:1ZYW"
FT DISULFID 35..55
FT /evidence="ECO:0000269|PubMed:10493862,
FT ECO:0000269|PubMed:15321715, ECO:0000269|PubMed:16209876,
FT ECO:0000312|PDB:1DJT, ECO:0000312|PDB:1SN1,
FT ECO:0000312|PDB:1T7A, ECO:0000312|PDB:1T7B,
FT ECO:0000312|PDB:1T7E, ECO:0000312|PDB:1ZU3,
FT ECO:0000312|PDB:1ZUT, ECO:0000312|PDB:1ZVE,
FT ECO:0000312|PDB:1ZVG, ECO:0000312|PDB:1ZYV,
FT ECO:0000312|PDB:1ZYW"
FT DISULFID 41..65
FT /evidence="ECO:0000269|PubMed:10493862,
FT ECO:0000269|PubMed:15321715, ECO:0000269|PubMed:16209876,
FT ECO:0000312|PDB:1DJT, ECO:0000312|PDB:1SN1,
FT ECO:0000312|PDB:1T7A, ECO:0000312|PDB:1T7B,
FT ECO:0000312|PDB:1T7E, ECO:0000312|PDB:1ZU3,
FT ECO:0000312|PDB:1ZUT, ECO:0000312|PDB:1ZVE,
FT ECO:0000312|PDB:1ZVG, ECO:0000312|PDB:1ZYV,
FT ECO:0000312|PDB:1ZYW"
FT DISULFID 45..67
FT /evidence="ECO:0000269|PubMed:10493862,
FT ECO:0000269|PubMed:15321715, ECO:0000269|PubMed:16209876,
FT ECO:0000312|PDB:1DJT, ECO:0000312|PDB:1SN1,
FT ECO:0000312|PDB:1T7A, ECO:0000312|PDB:1T7B,
FT ECO:0000312|PDB:1T7E, ECO:0000312|PDB:1ZU3,
FT ECO:0000312|PDB:1ZUT, ECO:0000312|PDB:1ZVE,
FT ECO:0000312|PDB:1ZVG, ECO:0000312|PDB:1ZYV,
FT ECO:0000312|PDB:1ZYW"
FT MUTAGEN 20..22
FT /note="Missing: 7.7-fold decrease in toxicity to mice, 3.2-
FT fold decrease in activity on Nav1.5/SCN5A, and 17.2-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 20
FT /note="Missing: 1.2-fold decrease in toxicity to mice, 8.6-
FT fold decrease in activity on Nav1.5/SCN5A, and 2.5-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 21
FT /note="R->A: 2.4-fold decrease in toxicity to mice, 15.2-
FT fold decrease in activity on Nav1.5/SCN5A, and 43.3-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 21
FT /note="R->E: 2.5-fold decrease in toxicity to mice, 1.6-
FT fold decrease in activity on Nav1.5/SCN5A, and 22.3-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 22
FT /note="D->A: 1.3-fold decrease in toxicity to mice, 16.8-
FT fold decrease in activity on Nav1.5/SCN5A, and 7.5-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 22
FT /note="D->N: 1.4-fold increase in toxicity to mice, 1.4-
FT fold increase in activity on Nav1.5/SCN5A, and 3.9-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 24
FT /note="Y->F: 25-fold decrease in toxicity to mice."
FT /evidence="ECO:0000269|PubMed:12692120,
FT ECO:0000269|PubMed:12705833"
FT MUTAGEN 24
FT /note="Y->G: Complete loss of toxicity to mice, and 70-fold
FT decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12692120,
FT ECO:0000269|PubMed:12705833"
FT MUTAGEN 25
FT /note="I->G: >47-fold decrease in toxicity to mice, 2.4-
FT fold decrease in activity on Nav1.5/SCN5A, and 70-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 27..28
FT /note="KP->DS: 43.4-fold decrease in toxicity to mice, 170-
FT fold decrease in the binding affinity for insect sodium
FT channels."
FT MUTAGEN 27
FT /note="K->D: 118-fold decrease in toxicity to mice, and
FT 250-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833,
FT ECO:0000269|PubMed:15321715"
FT MUTAGEN 28..29
FT /note="PH->NY: 3.3-fold increase in toxicity to mice, 7-
FT fold decrease in activity on Nav1.5/SCN5A, and 5.1-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 28
FT /note="P->N: 1.9-fold increase in toxicity to mice, 1.3-
FT fold increase in activity on Nav1.5/SCN5A, and 24.1-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 28
FT /note="P->S: 1.8-fold decrease in toxicity to mice, and
FT 1.3-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833,
FT ECO:0000269|PubMed:15321715"
FT MUTAGEN 29
FT /note="H->E: 1.7-fold decrease in toxicity to mice, and
FT 0.8-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 29
FT /note="H->Y: 2.2-fold decrease in toxicity to mice, 6.8-
FT fold increase in activity on Nav1.5/SCN5A, and 1.8-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 30
FT /note="N->A: Complete loss of toxicity to mice, 380-fold
FT decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 40
FT /note="Y->G: 1.9-fold decrease in toxicity to mice, and
FT 1.4-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 47
FT /note="K->E: 4.1-fold decrease in toxicity to mice, and 14-
FT fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 53
FT /note="G->A: 38-fold decrease in toxicity to mice, 11.2-
FT fold decrease in activity on Nav1.5/SCN5A, and 43.3-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 57
FT /note="W->G: More than 50-fold decrease in toxicity to
FT mice."
FT /evidence="ECO:0000269|PubMed:12692120"
FT MUTAGEN 61
FT /note="Y->G: More than 50-fold decrease in toxicity to
FT mice."
FT /evidence="ECO:0000269|PubMed:12692120"
FT MUTAGEN 62
FT /note="G->A: >47-fold decrease in toxicity to mice, loss of
FT activity on Nav1.5/SCN5A, and 56.7-fold decrease in
FT activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 70
FT /note="L->G: >47-fold decrease in toxicity to mice, loss of
FT activity on Nav1.5/SCN5A, and 233.3-fold decrease in
FT activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 71
FT /note="P->S: Not tested in mice, 1.2-fold decrease in
FT activity on Nav1.5/SCN5A, and 16.9-fold decrease in
FT activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 72
FT /note="D->A: 0.6-fold decrease in toxicity to mice, and
FT 0.2-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 76
FT /note="I->G: 1.1-fold decrease in toxicity to mice, loss of
FT activity on Nav1.5/SCN5A, and 2.5-fold decrease in activity
FT on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 77
FT /note="R->A: Complete loss of toxicity to mice, and
FT complete loss of affinity for insect sodium channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 78
FT /note="V->G: 1.3-fold decrease in toxicity to mice, 2.6-
FT fold decrease in activity on Nav1.5/SCN5A, and 2.2-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 79
FT /note="P->A: 1.1-fold increase in toxicity to mice, 5.8-
FT fold decrease in activity on Nav1.5/SCN5A, and 20.4-fold
FT decrease in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 79
FT /note="P->G: 1.7-fold decrease in toxicity to mice, 1.3-
FT fold increase in activity on Nav1.5/SCN5A, and 1.7-fold
FT increase in activity on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 80
FT /note="G->A: 35-fold decrease in toxicity to mice, loss of
FT activity on Nav1.5/SCN5A, and 7.8-fold decrease in activity
FT on insect sodium channels."
FT /evidence="ECO:0000269|PubMed:15677695"
FT MUTAGEN 81
FT /note="K->E: 71.4-fold decrease in toxicity to mice, and
FT 170-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 83
FT /note="H->A: 3.8-fold decrease in toxicity to mice, and
FT 180-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 83
FT /note="H->D: 43.9-fold decrease in toxicity to mice, and
FT 96-fold decrease in the binding affinity for insect sodium
FT channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT MUTAGEN 83
FT /note="H->K: 1.9-fold decrease in toxicity to mice, and
FT 11.5-fold decrease in the binding affinity for insect
FT sodium channels."
FT /evidence="ECO:0000269|PubMed:12705833"
FT CONFLICT 48
FT /note="N -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:1DJT"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:1DJT"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:1DJT"
FT STRAND 51..59
FT /evidence="ECO:0007829|PDB:1DJT"
FT STRAND 62..70
FT /evidence="ECO:0007829|PDB:1DJT"
SQ SEQUENCE 84 AA; 9496 MW; F8F14623AB2549A2 CRC64;
MNYLVMISFA LLLMTGVESV RDAYIAKPHN CVYECARNEY CNDLCTKNGA KSGYCQWVGK
YGNGCWCIEL PDNVPIRVPG KCHR
