Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Alpha-like toxin BmK-M1

Gene
N/A
Organism
Mesobuthus martensii (Manchurian scorpion) (Buthus martensii)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This alpha-like toxin binds voltage-dependently sodium channels and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals and insects. Is active on Nav1.4/SCN4A and Nav1.5/SCN5A. Acts as a cardiotoxin. Is 6-fold more toxic than BmK-M2.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Protein family/group databases

TCDBi8.B.1.1.1. the long (4c-c) scorpion toxin (l-st) superfamily.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-like toxin BmK-M1
Alternative name(s):
BmK I
BmK-I
Short name:
BmKI
BmK1
Bmk M1
Short name:
BmKM1
OrganismiMesobuthus martensii (Manchurian scorpion) (Buthus martensii)
Taxonomic identifieri34649 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeMesobuthus

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Toxic dosei

LD50 is 0.75 mg/kg by intravenous injection into mice.1 Publication
LD50 is 0.53 mg/kg by intravenous injection into tail mice.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 241Y → F: 25-fold decrease in toxicity to mice. 2 Publications
Mutagenesisi24 – 241Y → G: Complete loss of toxicity to mice, and 70-fold decrease in the binding affinity for insect sodium channels. 2 Publications
Mutagenesisi27 – 282KP → DS: 43.4-fold decrease in toxicity to mice, 170-fold decrease in the binding affinity for insect sodium channels.
Mutagenesisi27 – 271K → D: 118-fold decrease in toxicity to mice, and 250-fold decrease in the binding affinity for insect sodium channels. 2 Publications
Mutagenesisi28 – 281P → S: 1.8-fold decrease in toxicity to mice, and 1.3-fold decrease in the binding affinity for insect sodium channels. 2 Publications
Mutagenesisi29 – 291H → E: 1.7-fold decrease in toxicity to mice, and 0.8-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi30 – 301N → A: Complete loss of toxicity to mice, 380-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi40 – 401Y → G: 1.9-fold decrease in toxicity to mice, and 1.4-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi47 – 471K → E: 4.1-fold decrease in toxicity to mice, and 14-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi57 – 571W → G: More than 50-fold decrease in toxicity to mice. 1 Publication
Mutagenesisi61 – 611Y → G: More than 50-fold decrease in toxicity to mice. 1 Publication
Mutagenesisi72 – 721D → A: 0.6-fold decrease in toxicity to mice, and 0.2-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi77 – 771R → A: Complete loss of toxicity to mice, and complete loss of affinity for insect sodium channels. 1 Publication
Mutagenesisi81 – 811K → E: 71.4-fold decrease in toxicity to mice, and 170-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi83 – 831H → A: 3.8-fold decrease in toxicity to mice, and 180-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi83 – 831H → D: 43.9-fold decrease in toxicity to mice, and 96-fold decrease in the binding affinity for insect sodium channels. 1 Publication
Mutagenesisi83 – 831H → K: 1.9-fold decrease in toxicity to mice, and 11.5-fold decrease in the binding affinity for insect sodium channels. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 19191 PublicationAdd
BLAST
Chaini20 – 8364Alpha-like toxin BmK-M1PRO_0000035236Add
BLAST
Propeptidei84 – 841Removed by a carboxypeptidaseCuratedPRO_0000035237

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi31 ↔ 82
Disulfide bondi35 ↔ 55
Disulfide bondi41 ↔ 65
Disulfide bondi45 ↔ 67

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.

Structurei

Secondary structure

1
84
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi21 – 277Combined sources
Turni28 – 303Combined sources
Helixi38 – 4710Combined sources
Beta strandi51 – 599Combined sources
Beta strandi62 – 709Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DJTX-ray1.20A/B20-83[»]
1SN1X-ray1.70A20-83[»]
1T7AX-ray1.50A20-83[»]
1T7BX-ray1.85A20-83[»]
1T7EX-ray1.40A20-83[»]
1ZU3X-ray1.33A20-83[»]
1ZUTX-ray1.70A20-83[»]
1ZVEX-ray1.70A20-83[»]
1ZVGX-ray1.20A20-83[»]
1ZYVX-ray1.50A20-83[»]
1ZYWX-ray1.30A20-83[»]
ProteinModelPortaliP45697.
SMRiP45697. Positions 20-83.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP45697.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Family and domain databases

Gene3Di3.30.30.10. 1 hit.
InterProiIPR003614. Scorpion_toxin-like.
IPR018218. Scorpion_toxinL.
IPR002061. Scorpion_toxinL/defensin.
[Graphical view]
PfamiPF00537. Toxin_3. 1 hit.
[Graphical view]
PRINTSiPR00285. SCORPNTOXIN.
SMARTiSM00505. Knot1. 1 hit.
[Graphical view]
SUPFAMiSSF57095. SSF57095. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P45697-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNYLVMISFA LLLMTGVESV RDAYIAKPHN CVYECARNEY CNDLCTKNGA
60 70 80
KSGYCQWVGK YGNGCWCIEL PDNVPIRVPG KCHR
Length:84
Mass (Da):9,496
Last modified:December 15, 1998 - v2
Checksum:iF8F14623AB2549A2
GO

Sequence cautioni

The sequence AAA69557.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti48 – 481N → D AA sequence (PubMed:8896191).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF057554 Genomic DNA. Translation: AAC13693.1.
U28659 mRNA. Translation: AAA69557.1. Different initiation.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF057554 Genomic DNA. Translation: AAC13693.1.
U28659 mRNA. Translation: AAA69557.1. Different initiation.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DJTX-ray1.20A/B20-83[»]
1SN1X-ray1.70A20-83[»]
1T7AX-ray1.50A20-83[»]
1T7BX-ray1.85A20-83[»]
1T7EX-ray1.40A20-83[»]
1ZU3X-ray1.33A20-83[»]
1ZUTX-ray1.70A20-83[»]
1ZVEX-ray1.70A20-83[»]
1ZVGX-ray1.20A20-83[»]
1ZYVX-ray1.50A20-83[»]
1ZYWX-ray1.30A20-83[»]
ProteinModelPortaliP45697.
SMRiP45697. Positions 20-83.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

TCDBi8.B.1.1.1. the long (4c-c) scorpion toxin (l-st) superfamily.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP45697.

Family and domain databases

Gene3Di3.30.30.10. 1 hit.
InterProiIPR003614. Scorpion_toxin-like.
IPR018218. Scorpion_toxinL.
IPR002061. Scorpion_toxinL/defensin.
[Graphical view]
PfamiPF00537. Toxin_3. 1 hit.
[Graphical view]
PRINTSiPR00285. SCORPNTOXIN.
SMARTiSM00505. Knot1. 1 hit.
[Graphical view]
SUPFAMiSSF57095. SSF57095. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. "The cDNA and genomic DNA sequences of a mammalian neurotoxin from the scorpion Buthus martensii Karsch."
    Xiong Y.-M., Ling M.-H., Wang D.-C., Chi C.-W.
    Toxicon 35:1025-1031(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Tissue: Venom gland.
  2. "Two neurotoxins (BmK I and BmK II) from the venom of the scorpion Buthus martensi Karsch: purification, amino acid sequences and assessment of specific activity."
    Ji Y.-H., Mansuelle P., Terakawa S., Kopeyan C., Yanaihara N., Hsu K., Rochat H.
    Toxicon 34:987-1001(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 20-83, CHARACTERIZATION.
    Tissue: Venom.
  3. "Electrophysiological characterization of BmK M1, an alpha-like toxin from Buthus martensi Karsch venom."
    Goudet C., Huys I., Clynen E., Schoofs L., Wang D.C., Waelkens E., Tytgat J.
    FEBS Lett. 495:61-65(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: ELECTROPHYSIOLOGICAL CHARACTERIZATION, FUNCTION ON SCN5A SODIUM CHANNELS.
  4. "Exploration of the functional site of a scorpion alpha-like toxin by site-directed mutagenesis."
    Wang C.-G., Gilles N., Hamon A., Le Gall F., Stankiewicz M., Pelhate M., Xiong Y.-M., Wang D.-C., Chi C.-W.
    Biochemistry 42:4699-4708(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-24; LYS-27; PRO-28; HIS-29; ASN-30; TYR-40; LYS-47; ASP-72; ARG-77; LYS-81 AND HIS-83, FUNCTION ON SCN2A AND SCN4A SODIUM CHANNELS, LETHAL DOSE.
  5. "Importance of the conserved aromatic residues in the scorpion alpha-like toxin BmK M1: the hydrophobic surface region revisited."
    Sun Y.-M., Bosmans F., Zhu R.-H., Goudet C., Xiong Y.-M., Tytgat J., Wang D.-C.
    J. Biol. Chem. 278:24125-24131(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF TYR-24; TRP-57 AND TYR-61.
  6. "Molecular basis of the mammalian potency of the scorpion alpha-like toxin, BmK M1."
    Liu L.-H., Bosmans F., Maertens C., Zhu R.-H., Wang D.-C., Tytgat J.
    FASEB J. 19:594-596(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS.
  7. "A series of bioactivity-variant neurotoxins from scorpion Buthus martensii Karsch: purification, crystallization and crystallographic analysis."
    Li H.-M., Zhao T., Jin L., Wang M., Zhang Y., Wang D.-C.
    Acta Crystallogr. D 55:341-344(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CRYSTALLIZATION.
    Tissue: Venom.
  8. "Crystal structures of two alpha-like scorpion toxins: non-proline cis peptide bonds and implications for new binding site selectivity on the sodium channel."
    He X.-L., Li H.-M., Zeng Z.-H., Liu X.-Q., Wang M., Wang D.-C.
    J. Mol. Biol. 292:125-135(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 20-83.
  9. "Structural mechanism governing cis and trans isomeric states and an intramolecular switch for cis/trans isomerization of a non-proline peptide bond observed in crystal structures of scorpion toxins."
    Guan R.-J., Xiang Y., He X.-L., Wang C.-G., Wang M., Zhang Y., Sundberg E.J., Wang D.-C.
    J. Mol. Biol. 341:1189-1204(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 19-83, MUTAGENESIS OF LYS-27 AND PRO-28.
  10. "Structural basis for the voltage-gated Na+ channel selectivity of the scorpion alpha-like toxin BmK M1."
    Ye X., Bosmans F., Li C., Zhang Y., Wang D.-C., Tytgat J.
    J. Mol. Biol. 353:788-803(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 19-83, MUTAGENESIS.

Entry informationi

Entry nameiSCX1_MESMA
AccessioniPrimary (citable) accession number: P45697
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: December 15, 1998
Last modified: May 11, 2016
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

Exists in two forms, due to cis-trans isomerization at 28-Pro-His-29.
Has no effect on SCN2A (Nav1.2).1 Publication

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.