Alpha-like toxin BmK-M1 precursor - Mesobuthus martensii (Manchurian scorpion)

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P45697 (SCX1_MESMA) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 87. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names	Recommended name: Alpha-like toxin BmK-M1 Alternative name(s): BmK I BmK-I Short name=BmKI BmK1 Bmk M1 Short name=BmKM1
Organism	Mesobuthus martensii (Manchurian scorpion) (Buthus martensii)
Taxonomic identifier	34649 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Mesobuthus

Protein attributes

Sequence length	84 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Has no effect on SCN2A (Nav1.2), but is active on SCN4A (Nav1.4) and (Nav1.5). Acts as a cardiotoxin. Is 6-fold more toxic than BmK-M2. Ref.3 Ref.4
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Toxic dose	LD₅₀ is 0.75 mg/kg by intravenous injection into mice. Ref.4 LD₅₀ is 0.53 mg/kg by intravenous injection into tail mice. Ref.4
Miscellaneous	Exists in two forms, due to cis-trans isomerization at 28-Pro-His-29.
Sequence similarities	Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.
Sequence caution	The sequence AAA69557.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Ion channel impairing toxin Neurotoxin Sodium channel inhibitor Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological_process	defense response Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sodium channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

Ref.2

Chain

20 – 83

Alpha-like toxin BmK-M1

PRO_0000035236

Propeptide

Removed by a carboxypeptidase Probable

PRO_0000035237

Amino acid modifications

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Experimental info

Mutagenesis

Y → F: 25-fold decrease in toxicity to mice. Ref.4 Ref.5

Mutagenesis

Y → G: Complete loss of toxicity to mice, and 70-fold decrease in the binding affinity for insect sodium channels. Ref.4 Ref.5

Mutagenesis

27 – 28

KP → DS: 43.4-fold decrease in toxicity to mice, 170-fold decrease in the binding affinity for insect sodium channels. Ref.4 Ref.9

Mutagenesis

K → D: 118-fold decrease in toxicity to mice, and 250-fold decrease in the binding affinity for insect sodium channels. Ref.4 Ref.9

Mutagenesis

P → S: 1.8-fold decrease in toxicity to mice, and 1.3-fold decrease in the binding affinity for insect sodium channels. Ref.4 Ref.9

Mutagenesis

H → E: 1.7-fold decrease in toxicity to mice, and 0.8-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

N → A: Complete loss of toxicity to mice, 380-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

Y → G: 1.9-fold decrease in toxicity to mice, and 1.4-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

K → E: 4.1-fold decrease in toxicity to mice, and 14-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

W → G: More than 50-fold decrease in toxicity to mice. Ref.5

Mutagenesis

Y → G: More than 50-fold decrease in toxicity to mice. Ref.5

Mutagenesis

D → A: 0.6-fold decrease in toxicity to mice, and 0.2-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

R → A: Complete loss of toxicity to mice, and complete loss of affinity for insect sodium channels. Ref.4

Mutagenesis

K → E: 71.4-fold decrease in toxicity to mice, and 170-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

H → A: 3.8-fold decrease in toxicity to mice, and 180-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

H → D: 43.9-fold decrease in toxicity to mice, and 96-fold decrease in the binding affinity for insect sodium channels. Ref.4

Mutagenesis

H → K: 1.9-fold decrease in toxicity to mice, and 11.5-fold decrease in the binding affinity for insect sodium channels. Ref.4

Sequence conflict

N → D AA sequence Ref.2

Secondary structure

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P45697 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: F8F14623AB2549A2
Show »

FASTA

9,496

        10         20         30         40         50         60 
MNYLVMISFA LLLMTGVESV RDAYIAKPHN CVYECARNEY CNDLCTKNGA KSGYCQWVGK 

        70         80 
YGNGCWCIEL PDNVPIRVPG KCHR

« Hide

References

[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF057554 Genomic DNA. Translation: AAC13693.1.
U28659 mRNA. Translation: AAA69557.1. Different initiation.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DJT	X-ray	1.20	A/B	20-83	[»]
1SN1	X-ray	1.70	A	20-83	[»]
1T7A	X-ray	1.50	A	19-83	[»]
1T7B	X-ray	1.85	A	19-83	[»]
1T7E	X-ray	1.40	A	19-83	[»]
1ZU3	X-ray	1.33	A	19-83	[»]
1ZUT	X-ray	1.70	A	19-83	[»]
1ZVE	X-ray	1.70	A	19-83	[»]
1ZVG	X-ray	1.20	A	19-83	[»]
1ZYV	X-ray	1.50	A	19-83	[»]
1ZYW	X-ray	1.30	A	19-83	[»]

ProteinModelPortal

P45697.

SMR

P45697. Positions 20-83.

ModBase

Search...

Protein family/group databases

TCDB

8.B.1.1.1. long (4C-C) scorpion toxin (L-ST) superfamily.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

3.30.30.10. 1 hit.

InterPro

IPR003614. Scorpion_toxin-like.
IPR018218. Scorpion_toxinL.
IPR002061. Scorpion_toxinL/defesin.
[Graphical view]

Pfam

PF00537. Toxin_3. 1 hit.
[Graphical view]

PRINTS

PR00285. SCORPNTOXIN.

SMART

SM00505. Knot1. 1 hit.
[Graphical view]

SUPFAM

SSF57095. SSF57095. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P45697.

Entry information

Entry name

SCX1_MESMA

Accession

Primary (citable) accession number: P45697

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	December 15, 1998
Last modified:	May 1, 2013
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

Protocols and materials databases

Family and domain databases

Other

Entry information

Relevant documents