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P84646 (SCX1_ODODO) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 37. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-toxin OD1
OrganismOdontobuthus doriae (Yellow Iranian scorpion)
Taxonomic identifier342590 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeOdontobuthus

Protein attributes

Sequence length65 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Alpha toxins bind voltage-independently at site-3 of sodium channels and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. Mammalian sodium channels Nav1.7/SCN9A (EC50=4.5 nM), Nav1.4/SCN4A (EC50=9.6 nM), Nav1.6/SCN8A (EC50=30 nM) Nav1.5/SCN5A (only at micromolar concentrations), and insect sodium channel para/tipE (EC50=80 nM) are affected by this toxin. Ref.1 Ref.2 Ref.3

Subcellular location

Secreted Ref.1.

Tissue specificity

Expressed by the venom gland. Ref.1

Miscellaneous

Mammalian sodium channels Nav1.2/SCN2A, Nav1.3/SCN3A, and Nav1.8/SCN10A are unaffected by high concentrations (Ref.1 and Ref.2).

Sequence similarities

Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.

Mass spectrometry

Molecular mass is 7204.8 Da from positions 1 - 65. Determined by MALDI. With amidation. Ref.1

Ontologies

Keywords
   Cellular componentSecreted
   Molecular functionIon channel impairing toxin
Neurotoxin
Toxin
Voltage-gated sodium channel impairing toxin
   PTMAmidation
Disulfide bond
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological_processdefense response

Inferred from electronic annotation. Source: InterPro

   Cellular_componentextracellular region

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionsodium channel inhibitor activity

Inferred from direct assay Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 6565Alpha-toxin OD1
PRO_0000066788

Regions

Motif9 – 113Important for toxin selectivity for individual Nav channel subtype (Nav1.6 and Nav1.7), but not for toxin potency

Sites

Site61Important for toxin potency but not for selectivity for individual Nav channel subtype (Nav1.6 and Nav1.7)

Amino acid modifications

Modified residue651Arginine amide Ref.1
Disulfide bond13 ↔ 64 Ref.3 UniProtKB P45697
Disulfide bond17 ↔ 37 Ref.3 UniProtKB P45697
Disulfide bond23 ↔ 47 Ref.3 UniProtKB P45697
Disulfide bond27 ↔ 49 Ref.3 UniProtKB P45697

Experimental info

Mutagenesis61Y → F: Decrease in potency of about 10-fold, without affecting the selectivity for Nav1.4, Nav1.6 and Nav1.7. Ref.3
Mutagenesis9 – 113DDK → KPH: Increase in potency for Nav1.4 (1.6-fold) and Nav1.7 (2.3-fold) and decrease in potency for Nav1.6 (fold), resulting in a 40-fold increase of selectivity for Nav1.7 over Nav1.6. No change in potency for Nav1.4 and Nav1.6, and important increase in potency for Nav1.7 (11.7-fold); when associated with A-55. Ref.3
Mutagenesis111K → V: Increase in potency for Nav1.4 (5-fold) and Nav1.6 (7.8-fold) and decrease in potency for Nav1.7 (4.3-fold), resulting in a 5-fold increase of selectivity for Nav1.6 over Nav1.7. Increase in potency for Nav1.6 (16-fold), no change in potency for Nav1.7, and decrease in potency for Nav1.4 (1.6-fold); when associated with A-55. Ref.3
Mutagenesis511K → A: No change in potency for Nav1.4, Nav1.6 and Nav1.7. Ref.3
Mutagenesis551E → A: No change in potency for Nav1.4 and Nav1.7, and important decrease in potency for Nav1.6 (2.3-fold), resulting in a 13-fold increase of selectivity for Nav1.4 and Nav1.7 over Nav1.6. No change in potency for Nav1.4; Nav1.6, and important increase in potency for Nav1.7 (11.7-fold); when associated with 9-K--H-11. Increase in potency for Nav1.6 (16-fold), no change in potency for Nav1.7, and decrease in potency for Nav1.4 (1.6-fold); when associated with V-11. Ref.3
Mutagenesis551E → H: No change in potency for Nav1.4 and Nav1.7, and decrease in potency for Nav1.6 (1.7-fold). Ref.3
Mutagenesis601I → G: No change in potency for Nav1.4, and decrease in potency for Nav1.6 (1.6-fold) and Nav1.7 (2.6-fold). Ref.3

Secondary structure

........... 65
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P84646 [UniParc].

Last modified October 11, 2005. Version 1.
Checksum: FF76362F0C7ACCE7

FASTA657,215
        10         20         30         40         50         60 
GVRDAYIADD KNCVYTCASN GYCNTECTKN GAESGYCQWI GRYGNACWCI KLPDEVPIRI 


PGKCR 

« Hide

References

[1]"OD1, the first toxin isolated from the venom of the scorpion Odonthobuthus doriae active on voltage-gated Na+ channels."
Jalali A., Bosmans F., Amininasab M., Clynen E., Cuypers E., Zaremirakabadi A., Sarbolouki M.N., Schoofs L., Vatanpour H., Tytgat J.
FEBS Lett. 579:4181-4186(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE, FUNCTION, TOXIN TARGET, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY, AMIDATION AT ARG-65.
Tissue: Venom.
[2]"Potent modulation of the voltage-gated sodium channel Nav1.7 by OD1, a toxin from the scorpion Odonthobuthus doriae."
Maertens C., Cuypers E., Amininasab M., Jalali A., Vatanpour H., Tytgat J.
Mol. Pharmacol. 70:405-414(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOXIN TARGET.
[3]"Chemical Engineering and Structural and Pharmacological Characterization of the alpha-Scorpion Toxin OD1."
Durek T., Vetter I., Wang C.I., Motin L., Knapp O., Adams D.J., Lewis R.J., Alewood P.F.
ACS Chem. Biol. 8:1215-1222(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), SYNTHESIS, FUNCTION, TOXIN TARGET, DISULFIDE BONDS, MUTAGENESIS OF TYR-6; 9-ASP--LYS-11; LYS-11; LYS-51; GLU-55 AND ILE-60.

Cross-references

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4HHFX-ray1.80A1-65[»]
ProteinModelPortalP84646.
SMRP84646. Positions 2-64.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D3.30.30.10. 1 hit.
InterProIPR003614. Scorpion_toxin-like.
IPR018218. Scorpion_toxinL.
IPR002061. Scorpion_toxinL/defensin.
[Graphical view]
PfamPF00537. Toxin_3. 1 hit.
[Graphical view]
PRINTSPR00285. SCORPNTOXIN.
SMARTSM00505. Knot1. 1 hit.
[Graphical view]
SUPFAMSSF57095. SSF57095. 1 hit.
ProtoNetSearch...

Entry information

Entry nameSCX1_ODODO
AccessionPrimary (citable) accession number: P84646
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: October 11, 2005
Last modified: March 19, 2014
This is version 37 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references