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Protein

Potassium channel toxin gamma-KTx 1.1

Gene
N/A
Organism
Centruroides noxius (Mexican scorpion)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Blocks human and rat Kv11.1/KCNH2/ERG1 and Kv11.3/KCNH7/ERG3, as well as rat (but not human) Kv11.2/KCNH6/ERG2 (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425) by binding to channel outer vestibule (S5P domain) with a 1:1 stoichiometry (PubMed:11755529, PubMed:11864985, PubMed:17369411, PubMed:20600425). Inhibition data are the following: hERG1 (reversible, IC50~7 nM) (PubMed:11755529, PubMed:11864985, PubMed:16497878, PubMed:17369411, PubMed:20600425), rERG1 (reversible, Kd=6.8 nM) (PubMed:16497878), rERG2 (irreversible, Kd=2.8 nM) (PubMed:16497878), hERG3 (irreversible, Kd=4.05 nM) (PubMed:16497878) and rERG3 (reversible, Kd=38.1 nM) (PubMed:16497878) potassium channels. The toxin potency is not affected by elevating potassium ion concentration from 2 to 98 mM (PubMed:11864985). This toxin only blocks channels in a closed state (PubMed:12860380). At high toxin concentrations, block of Kv11.1/KCNH2/ERG1 macroscopic current is incomplete (93.5%). This suggests a kinetic mechanism model with two different states of toxin-channel binding (T+C=TC*=TC; in the TC* state, the toxin binds the channel but does not occlude the pore, whereas in the TC state the toxin binds and occludes the pore). In this model, incomplete block is explained by the relatively fast dissociation rate from the blocked channel conformation (TC) relative to the rate of conversion of the toxin-channel encounter complex (TC*) to the blocked channel conformation (TC) (PubMed:17369411).7 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei33May represent the binding site1 Publication1
Sitei55Key residue on the interacting surface with the channel1 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel impairing toxin, Neurotoxin, Potassium channel impairing toxin, Toxin, Voltage-gated potassium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Potassium channel toxin gamma-KTx 1.11 Publication
Alternative name(s):
Ergtoxin1 Publication
Short name:
CnErg11 Publication
Short name:
CnErgTx11 Publication
Short name:
ErgTx1 Publication
Short name:
ErgTx11 Publication
OrganismiCentruroides noxius (Mexican scorpion)
Taxonomic identifieri6878 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeCentruroides

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi38Q → A: 6-fold reduction in affinity for Kv11.1/KCNH2/ERG1 potassium channel (Kd=72.9 nM). 1 Publication1
Mutagenesisi55M → A: 30-fold reduction in affinity for Kv11.1/KCNH2/ERG1 potassium channel (Kd=303.4 nM). 1 Publication1
Mutagenesisi62A → T: No change in affinity for Kv11.1/KCNH2/ERG1 potassium channel (Kd=14.2 nM). 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000003536221 – 62Potassium channel toxin gamma-KTx 1.1Add BLAST42

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi25 ↔ 432 Publications
Disulfide bondi31 ↔ 542 Publications
Disulfide bondi40 ↔ 592 Publications
Disulfide bondi44 ↔ 612 Publications

Post-translational modificationi

After protein storage at -20 Celsius degrees during a couple of months, the Met-55 of a small number of toxins is naturally oxidized. This oxidized form is about three orders of magnitude less efficient (IC50=15 µM) than non-oxidized form.1 Publication

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.Curated

Structurei

Secondary structure

162
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi25 – 27Combined sources3
Beta strandi33 – 35Combined sources3
Helixi38 – 47Combined sources10
Beta strandi48 – 50Combined sources3
Beta strandi52 – 57Combined sources6
Beta strandi59 – 61Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NE5NMR-A21-62[»]
1PX9NMR-A21-62[»]
ProteinModelPortaliQ86QT3.
SMRiQ86QT3.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86QT3.

Family & Domainsi

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
Has the CSalpha/beta fold, which comprises one or two short alpha helices connected to anti-parallel beta-sheets stabilized by three or four disulfide bonds.2 Publications

Sequence similaritiesi

Belongs to the ergtoxin family. Gamma-KTx 1 subfamily.Curated

Keywords - Domaini

Knottin, Signal

Family and domain databases

Gene3Di3.30.30.10. 1 hit.
InterProiIPR012622. Ergtoxin.
IPR003614. Scorpion_toxin-like.
[Graphical view]
PfamiPF08086. Toxin_17. 1 hit.
[Graphical view]
ProDomiPD736966. Ergtoxin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF57095. SSF57095. 1 hit.
PROSITEiPS60026. ERGTX. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q86QT3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVLILIMII ASLMIMGVEM DRDSCVDKSR CAKYGYYQEC QDCCKNAGHN
60
GGTCMFFKCK CA
Length:62
Mass (Da):6,970
Last modified:June 1, 2003 - v1
Checksum:i53F88F4B9F187E37
GO

Mass spectrometryi

Molecular mass is 4730.8±0.4 Da from positions 21 - 62. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY164271 mRNA. Translation: AAO22234.1.
AF288205 mRNA. Translation: AAG38523.1.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY164271 mRNA. Translation: AAO22234.1.
AF288205 mRNA. Translation: AAG38523.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NE5NMR-A21-62[»]
1PX9NMR-A21-62[»]
ProteinModelPortaliQ86QT3.
SMRiQ86QT3.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiQ86QT3.

Family and domain databases

Gene3Di3.30.30.10. 1 hit.
InterProiIPR012622. Ergtoxin.
IPR003614. Scorpion_toxin-like.
[Graphical view]
PfamiPF08086. Toxin_17. 1 hit.
[Graphical view]
ProDomiPD736966. Ergtoxin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF57095. SSF57095. 1 hit.
PROSITEiPS60026. ERGTX. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKGX11_CENNO
AccessioniPrimary (citable) accession number: Q86QT3
Secondary accession number(s): Q9GQ92
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: June 1, 2003
Last modified: November 2, 2016
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

The affinity of the toxin for the channel decreases as temperature increases (Kd=7.3 nM and Kd=64 nM at 22 and 37 degrees Celsius, respectively), likely due to changes in the structure of the channel binding site.1 Publication
Does not affect the function of either mouse EAG/KCNH1 or ELK1 channels at concentration of 200 nM (PubMed:11755529). Does not inhibit hKv1.4/KCNA4, hKv4.3/KCND3, hKv2.1/KCNB1 and rKv7.1/KCNQ1 potassium channels at concentration of 50 nM (PubMed:11864985). Does not inhibit human Kv11.2/KCNH6/ERG2 (PubMed:16497878).3 Publications

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. Scorpion potassium channel toxins
    Nomenclature of scorpion potassium channel toxins and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.