P55896 (KAX37_ORTSC) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Potassium channel toxin alpha-KTx 3.7 Alternative name(s): OsK-1 Short name=OsK1
Organism	Orthochirus scrobiculosus (Central Asian scorpion)
Taxonomic identifier	6892 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Orthochirus

Protein attributes

Sequence length	38 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Blocks voltage-gated potassium channels Kv1.1/KCNA1 (IC50=0.6nM), Kv1.2/KCNA2 (IC50=5.4nM), Kv1.3/KCNA3 (IC50=0.014nM) potently, and moderately block intermediate conductance calcium-activated potassium channels KCa3.1/KCNN4 (IC50=225nM). At high concentration (2 mM), is also active on Kv1.6/KCNA6 and Shaker IR. Ref.1 Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Toxic dose	LD50 is 2 µg/kg by intracerebroventricular injection into mice. Ref.2
Miscellaneous	Is inactive on Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.7/KCNA7, Kv3.1/KCNC1, Kv11.x/KCNH, KCa1.1/KCNMA1, KCa2.1/KCNN1, KCa2.2/KCNN2, and KCa2.3/KCNN3 (Ref.1 and Ref.2).
Sequence similarities	Belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 3 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 – 38

38

Potassium channel toxin alpha-KTx 3.7

PRO_0000044909

Amino acid modifications

Disulfide bond

8 ↔ 28

Ref.4

Disulfide bond

14 ↔ 33

Ref.4

Disulfide bond

18 ↔ 35

Ref.4

Experimental info

Mutagenesis

12

1

R → P: Loss of activity; when associated with K-16 and D-20. Ref.2

Mutagenesis

16

1

E → K: No change in activity. 1 to 2-fold increase in activity on Kv1.1, Kv1.2 and Kv1.3 without affecting activity on KCa3.1; when associated with K-20. Loss of activity; when associated with R-12 and D-20. Loss of activity; when associated with D-20 and T-36. Ref.2

Mutagenesis

20

1

K → D: 3-fold reduction of activity. 1 to 2-fold increase in activity on Kv1.1, Kv1.2 and Kv1.3 without affecting activity on KCa3.1; when associated with E-16. Loss of activity; when associated with R-12 and K-16. Loss of activity; when associated with K-16 and T-36. Ref.2

Mutagenesis

36

1

T → Y: Loss of activity; when associated with K-16 and D-20. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

38

Helix Strand Turn

Details...

Beta strand

2 – 4

3

Helix

11 – 21

11

Beta strand

23 – 29

7

Beta strand

32 – 37

6

Sequences

	Sequence		Length	Mass (Da)
	P55896 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 4E900CFE46E17421	FASTA	38	4,211
	10 20 30 GVIINVKCKI SRQCLEPCKK AGMRFGKCMN GKCHCTPK

References

[1]	"Structure and function of the potassium channel inhibitor from black scorpion venom." Grishin E.V., Korolkova Y.V., Kozlov S.A., Lipkin A.V., Nosyreva E.D., Pluzhnikov K.A., Sukhanov S.V., Volkova T.M. Pure Appl. Chem. 68:2105-2109(1996) Cited for: PROTEIN SEQUENCE, FUNCTION. Tissue: Venom.
[2]	"K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom." Mouhat S., Visan V., Ananthakrishnan S., Wulff H., Andreotti N., Grissmer S., Darbon H., De Waard M., Sabatier J.-M. Biochem. J. 385:95-104(2005) [PubMed: 15588251] [Abstract] Cited for: MUTAGENESIS OF ARG-12; GLU-16; LYS-20 AND THR-36, SYNTHESIS, LETHAL DOSE, FUNCTION.
[3]	"Pharmacological profiling of Orthochirus scrobiculosus toxin 1 analogs with a trimmed N-terminal domain." Mouhat S., Teodorescu G., Homerick D., Visan V., Wulff H., Wu Y., Grissmer S., Darbon H., De Waard M., Sabatier J.-M. Mol. Pharmacol. 69:354-362(2006) [PubMed: 16234482] [Abstract] Cited for: MUTAGENESIS.
[4]	"Three-dimensional structure of toxin OSK1 from Orthochirus scrobiculosus scorpion venom." Jaravine V.A., Nolde D.E., Reibarkh M.J., Korolkova Y.V., Kozlov S.A., Pluzhnikov K.A., Grishin E.V., Arseniev A.S. Biochemistry 36:1223-1232(1997) [PubMed: 9063870] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1SCO	NMR	-	A	1-38	[»]
2CK4	NMR	-	A	1-38	[»]
2CK5	NMR	-	A	8-38	[»]

ProteinModelPortal

P55896.

SMR

P55896. Positions 1-38.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

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Family and domain databases

InterPro

IPR001947. Scorpion_toxinS.
[Graphical view]

Pfam

PF00451. Toxin_2. 1 hit.
[Graphical view]

PRINTS

PR00286. CHARYBDTOXIN.

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

KAX37_ORTSC

Accession

Primary (citable) accession number: P55896

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	November 16, 2011
This is version 63 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program