Reviewed, UniProtKB/Swiss-Prot O46028 (KA101_CENNO)

Names and origin

Protein names	Recommended name:     Potassium channel toxin alpha-KTx 10.1 Alternative name(s):     Cobatoxin-1       Short name=CoTx1     gtIX
Organism	Centruroides noxius (Mexican scorpion)
Taxonomic identifier	6878 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Centruroides

Protein attributes

Sequence length	62 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Blocks Shaker B (Sh) and voltage-gated potassium-channels Kv1.1 (KCNA1), Kv1.2 (KCNA2), Kv1.3 (KCNA3). Also inhibits small conductance calcium-activated potassium channels (KCNN) and intermediate conductance calcium-activated potassium channel (KCNN4). Does not inhibit Kv1.5 (KCNA5), nor Kv3.1 (KCNC1). Ref.2
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Toxic dose	LD50 is 25 µg/kg by intracerebroventricular injection into mice. Ref.2
Sequence similarities	Belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 10 subfamily.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Ionic channel inhibitor Neurotoxin Potassium channel inhibitor Toxin
PTM	Amidation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	defense response Inferred from electronic annotation. Source: InterPro pathogenesis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: InterPro
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

Signal peptide

1 – 22

22

By similarity

Propeptide

23 – 28

6

PRO_0000232655

Chain

29 – 60

32

Potassium channel toxin alpha-KTx 10.1

PRO_0000035327

Sites

Site

34

1

Important for the interaction with KCNA2 channel

Site

38

1

Important for the interaction with KCNA2 channel

Site

42

1

Important for the interaction with KCNA2 channel

Site

46

1

Important for the interaction with KCNA2 channel

Site

49

1

Important for the interaction with KCNA2 channel

Site

51

1

Important for the interaction with KCNA2 channel

Site

52

1

Important for the interaction with KCNA2 channel

Site

56

1

Important for the interaction with KCNA2 channel

Site

58

1

Important for the interaction with KCNA2 channel

Amino acid modifications

Modified residue

60

1

Tyrosine amide

Disulfide bond

31 ↔ 50

Ref.2

Disulfide bond

36 ↔ 55

Ref.2

Disulfide bond

40 ↔ 57

Ref.2

Experimental info

Mutagenesis

35 – 37

3

TCD → PCQ: Increases the toxicity (LD(50)=15 ug/kg). Inhibits KCNN with the same intensity. Inhibits more efficiently KCNN4, Sh KCNA1, KCNA2, and KCNA3 Ref.2

Secondary structure

1

.

.

.

.

.

.

.

62

Helix Strand Turn

Details...

Helix

33 – 41

9

Turn

42 – 44

3

Beta strand

45 – 51

7

Beta strand

54 – 58

5

Sequences

	Sequence		Length	Mass (Da)
	O46028-1 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: 32CEAE093B6971A0	FASTA	62	7,131
	10 20 30 40 50 60 MEGIAKITLI LLFLFVTMHT FANWNTEAAV CVYRTCDKDC KRRGYRSGKC INNACKCYPY GK

References

[1]

"Cobatoxins 1 and 2 from Centruroides noxius Hoffmann constitute a new subfamily of potassium-channel-blocking scorpion toxins." Selisko B., Garcia C., Becerril B., Gomez-Lagunas F., Garay C., Possani L.D. Eur. J. Biochem. 254:468-479(1998) [PubMed: 9688256] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Venom gland.

[2]

"Cobatoxin 1 from Centruroides noxius scorpion venom: chemical synthesis, three-dimensional structure in solution, pharmacology and docking on K+ channels." Jouirou B., Mosbah A., Visan V., Grissmer S., M'Barek S., Fajloun Z., Van Rietschoten J., Devaux C., Rochat H., Lippens G., El Ayeb M., De Waard M., Mabrouk K., Sabatier J.-M. Biochem. J. 377:37-49(2004) [PubMed: 14498829] [Abstract] Cited for: STRUCTURE BY NMR OF 29-60, DISULFIDE BONDS, FUNCTION, SYNTHESIS, LETHAL DOSE, MUTAGENESIS OF 35-THR--ASP-37.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AJ224689 mRNA. Translation: CAA12073.1.

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PJV	NMR	-	A	29-60	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR003614. Knot1.
IPR001947. Scorpion_toxinS.
[Graphical view]

Pfam

PF00451. Toxin_2. 1 hit.
[Graphical view]

SMART

SM00505. Knot1. 1 hit.
[Graphical view]

PROSITE

PS01138. SCORP_SHORT_TOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

KA101_CENNO

Accession

Primary (citable) accession number: O46028

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 19, 2001
Last sequence update:	June 1, 1998
Last modified:	November 25, 2008
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Tox-Prot (Toxin Annotation Project)