P60980 (VSTX1_GRARO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Kappa-theraphotoxin-Gr3a Short name=Kappa-TRTX-Gr3a Alternative name(s): Voltage sensor toxin 1 Short name=VsTx1
Organism	Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata)
Taxonomic identifier	432528 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Theraphosidae › Grammostola

Protein attributes

Sequence length	34 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Inhibits sodium channels Nav1.7/SCN9A and potassium channels Kv11.1/KCNH2. Also binds the voltage-sensor domain of the potassium channel KvAP (from the archaeon Aeropyrum pernix) with very slow apparent binding kinetics and affects channel gating. Reaches its target by dynamically partitioning into anionic or zwitterionic headgroup lipid membranes. May bind to the open state of KvAP. Ref.2 Ref.3 Ref.4 Ref.5
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Domain	The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Miscellaneous	Does not inhibit potassium channels Kv1.1/KCNA1 (IC50>200 µM), Kv1.4/KCNA4 (IC50>200 µM), Kv11.2/KCNH6 (IC50=45 µM) and Kv11.3/KCNH7 (IC50=55 µM) and sodium channels Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A (Ref.2).
Sequence similarities	Belongs to the huwentoxin-1 family.
Mass spectrometry	Molecular mass is 3997.0 Da from positions 1 - 34. Ref.2

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin
Molecular function	Ion channel impairing toxin Neurotoxin Potassium channel inhibitor Sodium 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 sodium 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 – 34

34

Kappa-theraphotoxin-Gr3a

PRO_0000045008

Amino acid modifications

Disulfide bond

2 ↔ 16

Ref.6

Disulfide bond

9 ↔ 21

Ref.6

Disulfide bond

15 ↔ 28

Ref.6

Secondary structure

1

.

.

.

.

.

.

.

34

Helix Strand Turn

Details...

Beta strand

10 – 12

3

Beta strand

19 – 22

4

Turn

23 – 26

4

Beta strand

27 – 30

4

Sequences

	Sequence		Length	Mass (Da)
	P60980 [UniParc]. Last modified April 26, 2004. Version 1. Checksum: 800AF52DA953C078	FASTA	34	4,004
	10 20 30 ECGKFMWKCK NSNDCCKDLV CSSRWKWCVL ASPF

References

[1]	"Functional analysis of an archaebacterial voltage-dependent K+ channel." Ruta V., Jiang Y., Lee A., Chen J., MacKinnon R. Nature 422:180-185(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, MASS SPECTROMETRY. Tissue: Venom.
[2]	"Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels." Redaelli E., Cassulini R.R., Silva D.F., Clement H., Schiavon E., Zamudio F.Z., Odell G., Arcangeli A., Clare J.J., Alagon A., de la Vega R.C., Possani L.D., Wanke E. J. Biol. Chem. 285:4130-4142(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, MASS SPECTROMETRY, FUNCTION, TOXIN TARGET.
[3]	"A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom." Lee S.-Y., MacKinnon R. Nature 430:232-235(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Localization of the voltage-sensor toxin receptor on KvAP." Ruta V., MacKinnon R. Biochemistry 43:10071-10079(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. Tissue: Venom.
[5]	"Vstx1, a modifier of Kv channel gating, localizes to the interfacial region of lipid bilayers." Bemporad D., Sands Z.A., Wee C.L., Grottesi A., Sansom M.S. Biochemistry 45:11844-11855(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel." Jung H.J., Lee J.Y., Kim S.H., Eu Y.-J., Shin S.Y., Milescu M., Swartz K.J., Kim J.I. Biochemistry 44:6015-6023(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS, MEMBRANE-PARTITIONING, SYNTHESIS.

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1S6X	NMR	-	A	1-34	[»]

ProteinModelPortal

P60980.

SMR

P60980. Positions 1-34.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Organism-specific databases

ArachnoServer

AS000423. kappa-theraphotoxin-Gr3a.

Family and domain databases

InterPro

IPR013140. Huwentoxin_CS1.
IPR011696. Ion_channel_inhibitory.
[Graphical view]

Pfam

PF07740. Toxin_12. 1 hit.
[Graphical view]

PROSITE

PS60021. HWTX_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P60980.

Entry information

Entry name

VSTX1_GRARO

Accession

Primary (citable) accession number: P60980

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 26, 2004
Last sequence update:	April 26, 2004
Last modified:	March 6, 2013
This is version 42 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program