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Q10726 (KAX61_PANIM) Reviewed, UniProtKB/Swiss-Prot

Last modified October 16, 2013. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
Potassium channel toxin alpha-KTx 6.1
Alternative name(s):
PiTX-K-gamma
Potassium channel-blocking toxin 1
Short name=Pi-1
Short name=Pi1
OrganismPandinus imperator (Emperor scorpion)
Taxonomic identifier55084 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesIuridaScorpionoideaScorpionidaeScorpioninaePandinus

Protein attributes

Sequence length35 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Potently and reversibly inhibits the insect voltage-gated Shaker (Sh) potassium channel (isoform alpha(B)), the mammalian voltage-gated potassium channels Kv1.2/KCNA2. Its effect on Kv1.3/KCNA3 is controversial, since this channel is voltage-independently inhibited in Ref.4, but is not affected in Ref.5. Furthermore, this toxin competes with apamin (a small conductance calcium-activated potassium channel inhibitor) for binding onto rat brain synaptosomes. Ref.1 Ref.3 Ref.4 Ref.5

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom gland.

Domain

Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CSalpha/beta).

The alpha-helical domain may play a key role in the recognition of SK channels.

The beta-sheet structure may be involved in bioactivity on Kv channels.

Toxic dose

LD50 is 10 µg/kg by intraperitoneal injection into mice. Ref.5

Miscellaneous

Pi1 analog that is synthesized with a phosphorylation at Tyr-33 (P-Pi1) suffers a 200-fold decrease in LD50, a 200-fold decrease of potency in competition assay with apamin, and a 58-fold decrease in inhibiting Kv1.2/KCNA2 channels.

This toxin has no effect on Kv1.1/KCNA1 (Ref.5).

Sequence similarities

Belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 6 subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Peptide1 – 3535Potassium channel toxin alpha-KTx 6.1
PRO_0000044912

Sites

Site51Part of the basic ring which may anchor to the external vestibule of the K(+) channel
Site121Part of the basic ring which may anchor to the external vestibule of the K(+) channel
Site241Basic residue of the functional dyad
Site281Part of the basic ring which may anchor to the external vestibule of the K(+) channel
Site311Part of the basic ring which may anchor to the external vestibule of the K(+) channel
Site331Aromatic residue of the functional dyad

Amino acid modifications

Disulfide bond4 ↔ 25 Ref.1 Ref.7 Ref.8
Disulfide bond10 ↔ 30 Ref.1 Ref.7 Ref.8
Disulfide bond14 ↔ 32 Ref.1 Ref.7 Ref.8
Disulfide bond20 ↔ 35 Ref.1 Ref.7 Ref.8

Experimental info

Mutagenesis51R → A: 51-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-12. 479-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-31. Ref.6
Mutagenesis121R → A: 51-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-5. Ref.6
Mutagenesis241K → A: 500-fold decrease in LD(50), 600-fold decrease of potency in competition assay with apamin, and 17000-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-33. Ref.6
Mutagenesis311K → A: 294-fold decrease in inhibiting Kv1.2/KCNA2 channels. 479-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-5. Ref.6
Mutagenesis331Y → A: 500-fold decrease in LD(50), 600-fold decrease of potency in competition assay with apamin, and 17,000-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-24. Ref.6

Secondary structure

........ 35
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q10726 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 208001C82B2C9800

FASTA353,843
        10         20         30 
LVKCRGTSDC GRPCQQQTGC PNSKCINRMC KCYGC 

« Hide

References

[1]"A novel structural class of K+-channel blocking toxin from the scorpion Pandinus imperator."
Olamendi-Portugal T., Gomez-Lagunas F., Gurrola G.B., Possani L.D.
Biochem. J. 315:977-981(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE, FUNCTION, TOXIN TARGET, DISULFIDE BONDS.
Tissue: Venom.
[2]"Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels."
Rogowski R.S., Collins J.H., O'Neill T.J., Gustafson T.A., Werkman T.R., Rogawski M.A., Tenenholz T.C., Weber D.J., Blaustein M.P.
Mol. Pharmacol. 50:1167-1177(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE.
Tissue: Venom.
[3]"Block of ShakerB K+ channels by Pi1, a novel class of scorpion toxin."
Gomez-Lagunas F., Olamendi-Portugal T., Possani L.D.
FEBS Lett. 400:197-200(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOXIN TARGET.
[4]"Pandinus imperator scorpion venom blocks voltage-gated K+ channels in human lymphocytes."
Peter M. Jr., Varga Z., Panyi G., Bene L., Damjanovich S., Pieri C., Possani L.D., Gaspar R. Jr.
Biochem. Biophys. Res. Commun. 242:621-625(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOXIN TARGET.
[5]"Chemical synthesis and characterization of Pi1, a scorpion toxin from Pandinus imperator active on K+ channels."
Fajloun Z., Carlier E., Lecomte C., Geib S., Di Luccio E., Bichet D., Mabrouk K., Rochat H., De Waard M., Sabatier J.M.
Eur. J. Biochem. 267:5149-5155(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TOXIN TARGET, LETHAL DOSE, SYNTHESIS.
[6]"The 'functional' dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels."
Mouhat S., Mosbah A., Visan V., Wulff H., Delepierre M., Darbon H., Grissmer S., De Waard M., Sabatier J.M.
Biochem. J. 377:25-36(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-5; ARG-12; LYS-24; LYS-31 AND TYR-33, SITES.
[7]"A novel potassium channel blocking toxin from the scorpion Pandinus imperator: a 1H NMR analysis using a nano-NMR probe."
Delepierre M., Prochnicka-Chalufour A., Possani L.D.
Biochemistry 36:2649-2658(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
[8]"The impact of the fourth disulfide bridge in scorpion toxins of the alpha-KTx6 subfamily."
Carrega L., Mosbah A., Ferrat G., Beeton C., Andreotti N., Mansuelle P., Darbon H., De Waard M., Sabatier J.M.
Proteins 61:1010-1023(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Cross-references

Sequence databases

PIRS69599.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WZ5NMR-A1-34[»]
ProteinModelPortalQ10726.
SMRQ10726. Positions 1-34.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D3.30.30.10. 1 hit.
InterProIPR003614. Scorpion_toxin-like.
IPR001947. Scorpion_toxinS_K_inh.
[Graphical view]
PfamPF00451. Toxin_2. 1 hit.
[Graphical view]
ProDomPD003586. Scorpion_toxinS. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF57095. SSF57095. 1 hit.
PROSITEPS01138. SCORP_SHORT_TOXIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ10726.

Entry information

Entry nameKAX61_PANIM
AccessionPrimary (citable) accession number: Q10726
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: October 16, 2013
This is version 82 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

Scorpion potassium channel toxins

Nomenclature of scorpion potassium channel toxins and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references