ID SCM1_OLIMR Reviewed; 84 AA. AC P45697; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 2. DT 02-SEP-2026, entry version 134. 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 Olivierus martensii (Manchurian scorpion) (Mesobuthus martensii). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Chelicerata; Arachnida; OC Scorpiones; Buthida; Buthoidea; Buthidae; Olivierus. 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.04-2485fje; 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: Negative results: has insignificant effect on CC Nav1.2/SCN2A. {ECO:0000269|PubMed:12705833, CC 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}; 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; 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 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; EXP:UniProtKB. DR GO; GO:0019871; F:sodium channel inhibitor activity; IEA:InterPro. DR GO; GO:0090729; F:toxin activity; IEA:InterPro. DR GO; GO:0006952; P:defense response; IEA:InterPro. DR CDD; cd23106; neurotoxins_LC_scorpion; 1. DR FunFam; 3.30.30.10:FF:000002; Alpha-like toxin BmK-M1; 1. DR Gene3D; 3.30.30.10; Knottin, scorpion toxin-like; 1. DR InterPro; IPR003614; Knottins. DR InterPro; IPR044062; LCN-type_CS_alpha_beta_dom. 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; Scorpion toxin-like; 1. DR PROSITE; PS51863; LCN_CSAB; 1. 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; -. 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, FT 3.2-fold decrease in activity on Nav1.5/SCN5A, and FT 17.2-fold 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, FT 8.6-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, FT 15.2-fold decrease in activity on Nav1.5/SCN5A, and FT 43.3-fold 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, FT 1.6-fold decrease in activity on Nav1.5/SCN5A, and FT 22.3-fold 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, FT 16.8-fold decrease in activity on Nav1.5/SCN5A, and FT 7.5-fold 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, FT 1.4-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, FT 2.4-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, FT 170-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, FT 7-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, FT 1.3-fold increase in activity on Nav1.5/SCN5A, and FT 24.1-fold 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, FT 6.8-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 FT 14-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, FT 11.2-fold decrease in activity on Nav1.5/SCN5A, and FT 43.3-fold 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, FT 2.6-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, FT 5.8-fold decrease in activity on Nav1.5/SCN5A, and FT 20.4-fold 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, FT 1.3-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 //