O46028 (KA101_CENNO) Reviewed, UniProtKB/Swiss-Prot

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	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › 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 (KCa3.1/KCNN4). Ref.1 Ref.2
Subcellular location	Secreted Ref.1 Ref.2.
Tissue specificity	Expressed by the venom gland. Ref.1 Ref.2
Domain	Has the structural arrangement of an alpha-helix connected to a beta-sheet by disulfide bonds (CSalpha/beta).
Toxic dose	LD50 is 25 µg/kg by intracerebroventricular injection into mice. Ref.2
Miscellaneous	This toxin does not inhibit Kv1.5/KCNA5 and Kv3.1/KCNC1 (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	Ion channel impairing toxin Neurotoxin Potassium channel inhibitor Toxin
PTM	Amidation Disulfide bond
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: 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

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 Kv1.2/KCNA2 channel

Site

38

1

Important for the interaction with Kv1.2/KCNA2 channel

Site

42

1

Important for the interaction with Kv1.2/KCNA2 channel

Site

46

1

Important for the interaction with Kv1.2/KCNA2 channel

Site

49

1

Basic residue of the functional dyad, important for the interaction with Kv1.2/KCNA2 channel

Site

51

1

Important for the interaction with Kv1.2/KCNA2 channel

Site

52

1

Important for the interaction with Kv1.2/KCNA2 channel

Site

56

1

Important for the interaction with Kv1.2/KCNA2 channel

Site

58

1

Aromatic residue of the functional dyad, important for the interaction with Kv1.2/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 [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. 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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 29-60, FUNCTION, DISULFIDE BONDS, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, LETHAL DOSE, SYNTHESIS OF 29-60, MUTAGENESIS OF 35-THR--ASP-37. Tissue: Venom.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ224689 mRNA. Translation: CAA12073.1.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

O46028.

SMR

O46028. Positions 29-60.

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]

SMART

SM00505. Knot1. 1 hit.
[Graphical view]

SUPFAM

SSF57095. SSF57095. 1 hit.

PROSITE

PS01138. SCORP_SHORT_TOXIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O46028.

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:	May 1, 2013
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program