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P84646

- SCX1_ODODO

UniProt

P84646 - SCX1_ODODO

Protein

Alpha-toxin OD1

Gene
N/A
Organism
Odontobuthus doriae (Yellow Iranian scorpion)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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 (EC(50)=4.5 nM), Nav1.4/SCN4A (EC(50)=9.6 nM), Nav1.6/SCN8A (EC(50)=30 nM) Nav1.5/SCN5A (only at micromolar concentrations), and insect sodium channel para/tipE (EC(50)=80 nM) are affected by this toxin.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei6 – 61Important for toxin potency but not for selectivity for individual Nav channel subtype (Nav1.6 and Nav1.7)

    GO - Molecular functioni

    1. sodium channel inhibitor activity Source: UniProtKB

    GO - Biological processi

    1. defense response Source: InterPro

    Keywords - Molecular functioni

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

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alpha-toxin OD1
    OrganismiOdontobuthus doriae (Yellow Iranian scorpion)
    Taxonomic identifieri342590 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeOdontobuthus

    Subcellular locationi

    Secreted 1 Publication

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi6 – 61Y → F: Decrease in potency of about 10-fold, without affecting the selectivity for Nav1.4, Nav1.6 and Nav1.7. 1 Publication
    Mutagenesisi9 – 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.
    Mutagenesisi11 – 111K → 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. 1 Publication
    Mutagenesisi51 – 511K → A: No change in potency for Nav1.4, Nav1.6 and Nav1.7. 1 Publication
    Mutagenesisi55 – 551E → 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. 1 Publication
    Mutagenesisi55 – 551E → H: No change in potency for Nav1.4 and Nav1.7, and decrease in potency for Nav1.6 (1.7-fold). 1 Publication
    Mutagenesisi60 – 601I → G: No change in potency for Nav1.4, and decrease in potency for Nav1.6 (1.6-fold) and Nav1.7 (2.6-fold). 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 6565Alpha-toxin OD1PRO_0000066788Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi13 ↔ 641 Publication
    Disulfide bondi17 ↔ 371 Publication
    Disulfide bondi23 ↔ 471 Publication
    Disulfide bondi27 ↔ 491 Publication
    Modified residuei65 – 651Arginine amide1 Publication

    Keywords - PTMi

    Amidation, Disulfide bond

    Expressioni

    Tissue specificityi

    Expressed by the venom gland.1 Publication

    Structurei

    Secondary structure

    1
    65
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi2 – 87
    Helixi20 – 2910
    Beta strandi33 – 397
    Helixi41 – 433
    Beta strandi45 – 539

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4HHFX-ray1.80A1-65[»]
    ProteinModelPortaliP84646.
    SMRiP84646. Positions 2-64.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi9 – 113Important for toxin selectivity for individual Nav channel subtype (Nav1.6 and Nav1.7), but not for toxin potency

    Sequence similaritiesi

    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.

    P84646-1 [UniParc]FASTAAdd to Basket

    « Hide

    GVRDAYIADD KNCVYTCASN GYCNTECTKN GAESGYCQWI GRYGNACWCI   50
    KLPDEVPIRI PGKCR 65
    Length:65
    Mass (Da):7,215
    Last modified:October 11, 2005 - v1
    Checksum:iFF76362F0C7ACCE7
    GO

    Mass spectrometryi

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

    Cross-referencesi

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4HHF X-ray 1.80 A 1-65 [» ]
    ProteinModelPortali P84646.
    SMRi P84646. Positions 2-64.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    Gene3Di 3.30.30.10. 1 hit.
    InterProi IPR003614. Scorpion_toxin-like.
    IPR018218. Scorpion_toxinL.
    IPR002061. Scorpion_toxinL/defensin.
    [Graphical view ]
    Pfami PF00537. Toxin_3. 1 hit.
    [Graphical view ]
    PRINTSi PR00285. SCORPNTOXIN.
    SMARTi SM00505. Knot1. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57095. SSF57095. 1 hit.
    ProtoNeti Search...

    Publicationsi

    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: Venom1 Publication.
    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.

    Entry informationi

    Entry nameiSCX1_ODODO
    AccessioniPrimary (citable) accession number: P84646
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 11, 2005
    Last sequence update: October 11, 2005
    Last modified: October 1, 2014
    This is version 38 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programAnimal Toxin Annotation Program

    Miscellaneousi

    Miscellaneous

    Mammalian sodium channels Nav1.2/SCN2A, Nav1.3/SCN3A, and Nav1.8/SCN10A are unaffected by high concentrations (PubMed:16038905 and PubMed:16641312).

    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

    External Data

    Dasty 3