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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › 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	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.

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Ion channel impairing toxin 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] [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

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

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

Gene3D

3.30.30.10. 1 hit.

InterPro

IPR003614. Scorpion_toxin-like.
IPR001947. Scorpion_toxinS_K_inh.
[Graphical view]

Pfam

PF00451. Toxin_2. 1 hit.
[Graphical view]

ProDom

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

SUPFAM

SSF57095. SSF57095. 1 hit.

PROSITE

PS01138. SCORP_SHORT_TOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q10726.

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:	May 1, 2013
This is version 79 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program