Potassium channel toxin gamma-KTx 1.1 precursor - Centruroides noxius (Mexican scorpion)

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

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

Sites

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Siteⁱ	33	May represent the binding site1 Publication		1
Siteⁱ	55	Key residue on the interacting surface with the channel1 Publication		1

GO - Molecular functionⁱ

potassium channel inhibitor activity Source: InterPro

Complete GO annotation...

GO - Biological processⁱ

defense response Source: InterPro
pathogenesis Source: InterPro

Complete GO annotation...

Keywordsⁱ

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

Molecular function

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
Organismⁱ	Centruroides noxius (Mexican scorpion)
Taxonomic identifierⁱ	6878 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Centruroides

Subcellular locationⁱ

Secreted
1 Publication
Manual assertion based on experiment inⁱ
- Ref.2
  "A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom."
  Gurrola G.B., Rosati B., Rocchetti M., Pimienta G., Zaza A., Arcangeli A., Olivotto M., Possani L.D., Wanke E.
  FASEB J. 13:953-962(1999) [PubMed] [Europe PMC] [Abstract]
  Cited for: PROTEIN SEQUENCE OF 21-62, FUNCTION, SUBCELLULAR LOCATION.

GO - Cellular componentⁱ

extracellular region Source: UniProtKB-SubCell

Complete GO annotation...

Keywords - Cellular componentⁱ

Secreted

Pathology & Biotechⁱ

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	38	Q → A: 6-fold reduction in affinity for Kv11.1/KCNH2/ERG1 potassium channel (Kd=72.9 nM). 1 Publication	1
Mutagenesisⁱ	55	M → A: 30-fold reduction in affinity for Kv11.1/KCNH2/ERG1 potassium channel (Kd=303.4 nM). 1 Publication	1
Mutagenesisⁱ	62	A → T: No change in affinity for Kv11.1/KCNH2/ERG1 potassium channel (Kd=14.2 nM). 1 Publication	1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Signal peptideⁱ	1 – 20	1 PublicationAdd BLAST		20
ChainⁱPRO_0000035362	21 – 62	Potassium channel toxin gamma-KTx 1.1Add BLAST		42

Amino acid modifications

Feature key	Position(s)	DescriptionActions
Disulfide bondⁱ	25 ↔ 43	2 Publications
Disulfide bondⁱ	31 ↔ 54	2 Publications
Disulfide bondⁱ	40 ↔ 59	2 Publications
Disulfide bondⁱ	44 ↔ 61	2 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

Legend: HelixTurnBeta strandPDB Structure known for this area

Show more details

Feature key	Position(s)	DescriptionActions	Length
Helixⁱ	25 – 27	Combined sources	3
Beta strandⁱ	33 – 35	Combined sources	3
Helixⁱ	38 – 47	Combined sources	10
Beta strandⁱ	48 – 50	Combined sources	3
Beta strandⁱ	52 – 57	Combined sources	6
Beta strandⁱ	59 – 61	Combined sources	3

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1NE5	NMR	-	A	21-62	[»]
	1PX9	NMR	-	A	21-62	[»]
ProteinModelPortalⁱ	Q86QT3.
SMRⁱ	Q86QT3.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q86QT3.

EvolutionaryTraceⁱ

Q86QT3.

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

Gene3Dⁱ	3.30.30.10. 1 hit.
InterProⁱ	View protein in InterPro IPR012622. Ergtoxin. IPR003614. Scorpion_toxin-like.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF08086. Toxin_17. 1 hit.
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD736966. Ergtoxin. 1 hit.
SUPFAMⁱ	SSF57095. SSF57095. 1 hit.
PROSITEⁱ	View protein in PROSITE PS60026. ERGTX. 1 hit.

Sequenceⁱ

Sequence statusⁱ: Complete.

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

Q86QT3-1 [UniParc]FASTA Add 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.

Select the link destinations:
EMBLⁱ
GenBankⁱ
DDBJⁱ

Links Updated

AY164271 mRNA. Translation: AAO22234.1.
AF288205 mRNA. Translation: AAG38523.1.

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.

Cross-referencesⁱ

Sequence databases

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

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: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	1NE5	NMR	-	A	21-62	[»]
	1PX9	NMR	-	A	21-62	[»]
ProteinModelPortalⁱ	Q86QT3.
SMRⁱ	Q86QT3.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q86QT3.

EvolutionaryTraceⁱ

Q86QT3.

Family and domain databases

Gene3Dⁱ	3.30.30.10. 1 hit.
InterProⁱ	View protein in InterPro IPR012622. Ergtoxin. IPR003614. Scorpion_toxin-like.
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF08086. Toxin_17. 1 hit.
ProDomⁱ	View protein in ProDom or Entries sharing at least one domain PD736966. Ergtoxin. 1 hit.
SUPFAMⁱ	SSF57095. SSF57095. 1 hit.
PROSITEⁱ	View protein in PROSITE PS60026. ERGTX. 1 hit.
ProtoNetⁱ	Search...

Entry informationⁱ

Entry nameⁱ	KGX11_CENNO
Accessionⁱ	Q86QT3Primary (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. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Animal Toxin Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Direct protein sequencing

Documents

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

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - Q86QT3 (KGX11_CENNO)

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Potassium channel toxin gamma-KTx 1.1

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including length and molecular weight.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequencei

<p>This subsection of the ‘Sequence’ section reports information derived from mass spectrometry experiments done on the entire protein or on biologically active derived peptide(s).<p><a href='/help/mass_spectrometry' target='_top'>More...</a></p>Mass spectrometryi

Sequence databases

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protocols and materials databases

Miscellaneous databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Documents

Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequenceⁱ

Mass spectrometryⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ