Q10726 (KAX61_PANIM) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended 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
Organism	Pandinus imperator (Emperor scorpion)
Taxonomic identifier	55084 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Iurida › Scorpionoidea › Scorpionidae › Scorpioninae › Pandinus

Protein attributes

Sequence length	35 AA.
Sequence status	Complete.
Protein existence	Evidence 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	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 synthetised 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.

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Ionic channel inhibitor Neurotoxin Potassium channel inhibitor Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	potassium 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

Peptide

1 – 35

35

Potassium channel toxin alpha-KTx 6.1

PRO_0000044912

Sites

Site

5

1

Part of the basic ring which may anchor to the external vestibule of the K(+) channel

Site

12

1

Part of the basic ring which may anchor to the external vestibule of the K(+) channel

Site

24

1

Basic residue of the functional dyad

Site

28

1

Part of the basic ring which may anchor to the external vestibule of the K(+) channel

Site

31

1

Part of the basic ring which may anchor to the external vestibule of the K(+) channel

Site

33

1

Aromatic residue of the functional dyad

Amino acid modifications

Disulfide bond

4 ↔ 25

Ref.1 Ref.7 Ref.8

Disulfide bond

10 ↔ 30

Ref.1 Ref.7 Ref.8

Disulfide bond

14 ↔ 32

Ref.1 Ref.7 Ref.8

Disulfide bond

20 ↔ 35

Ref.1 Ref.7 Ref.8

Experimental info

Mutagenesis

5

1

R → 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

Mutagenesis

12

1

R → A: 51-fold decrease in inhibiting Kv1.2/KCNA2 channels; when associated with A-5. Ref.6

Mutagenesis

24

1

K → 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

Mutagenesis

31

1

K → 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

Mutagenesis

33

1

Y → 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

1

.

.

.

.

.

.

.

.

35

Helix Strand Turn

Details...

Turn

6 – 10

5

Helix

11 – 17

7

Beta strand

24 – 26

3

Beta strand

29 – 31

3

Sequences

	Sequence		Length	Mass (Da)
	Q10726 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 208001C82B2C9800	FASTA	35	3,843
	10 20 30 LVKCRGTSDC GRPCQQQTGC PNSKCINRMC KCYGC

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: 8645186] [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: 8913348] [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: 9001397] [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: 9464266] [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: 10931199] [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: 12962541] [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: 9054572] [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: 16247791] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

PIR

S69599.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WZ5	NMR	-	A	1-34	[»]

ProteinModelPortal

Q10726.

SMR

Q10726. Positions 1-34.

ModBase

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Protocols and materials databases

StructuralBiologyKnowledgebase

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Family and domain databases

InterPro

IPR001947. Scorpion_toxinS.
[Graphical view]

ProDom

PD003586. Scorpion_toxinS. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS01138. SCORP_SHORT_TOXIN. 1 hit.
[Graphical view]

ProtoNet

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Entry information

Entry name

KAX61_PANIM

Accession

Primary (citable) accession number: Q10726

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 16, 2011
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program