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Protein

Kappa-theraphotoxin-Hm1a

Gene
N/A
Organism
Heteroscodra maculata (Togo starburst tarantula) (Togo starburst baboon spider)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Inhibitor of voltage-gated potassium channels, which inhibits Kv2.1/KCNB1, Kv2.2/KCNB2, Kv4.1/KCND1, Kv4.2/KCND2 and Kv4.3/KCND3 potassium channels (PubMed:12065754). May act by shifting activation of the channel to more depolarized voltages. The toxin binding sites may be situated on the S3-S4 extracellular linker of the channel (PubMed:12065754). One, two, three or four toxin molecules may bind the Kv2.1/KCNB1 channel (PubMed:12065754). May need to partition into the membrane in order to bind to the channel. Intracerebroventricular injection into mice induces convulsions, spasms, tremors, and death (PubMed:12065754). Specifically activates the voltage-gated sodium channel Nav1.1/SCN1A in somatosensory neurons to elicit acute pain and mechanical allodynia (PubMed:27281198). The toxin targets the S3b-S4 and S1-S2 loops of repeat IV of the channel to inhibit fast inactivation of Nav1.1/SCN1A, selectivity for Nav1.1/SCN1A depending on S1-S2 loops of repeat IV (PubMed:27281198).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei3May be involved in interaction with voltage sensorBy similarity1
Sitei5May be involved in interaction with voltage sensorBy similarity1
Sitei6May be involved in interaction with voltage sensorBy similarity1
Sitei22May be involved in interaction with voltage sensorBy similarity1
Sitei30Involved in active faceBy similarity1

GO - Molecular functioni

  • ion channel inhibitor activity Source: InterPro
  • sodium channel regulator activity Source: UniProtKB

GO - Biological processi

  • pathogenesis Source: UniProtKB
  • regulation of voltage-gated sodium channel activity Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

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

Protein family/group databases

TCDBi8.B.5.3.3. the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Kappa-theraphotoxin-Hm1a
Short name:
Kappa-TRTX-Hm1a
Alternative name(s):
Heteroscodratoxin-11 Publication
Short name:
HmTx11 Publication
OrganismiHeteroscodra maculata (Togo starburst tarantula) (Togo starburst baboon spider)
Taxonomic identifieri268413 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaAraneaeMygalomorphaeTheraphosidaeHeteroscodra

Organism-specific databases

ArachnoServeriAS000224. delta-theraphotoxin-Hm1a.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PeptideiPRO_00000450171 – 35Kappa-theraphotoxin-Hm1aAdd BLAST35

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi2 ↔ 16By similarity
Disulfide bondi9 ↔ 21By similarity
Disulfide bondi15 ↔ 28By similarity
Modified residuei35Serine amide1 Publication1

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.Curated

Structurei

Secondary structure

135
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni5 – 7Combined sources3
Helixi12 – 14Combined sources3
Turni23 – 26Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N6ONMR-A1-35[»]
ProteinModelPortaliP60992.
SMRiP60992.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni4 – 6Involved in active faceBy similarity3

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.By similarity

Sequence similaritiesi

Belongs to the huwentoxin-1 family. HaTx subfamily.Curated

Keywords - Domaini

Knottin

Family and domain databases

InterProiIPR011696. Huwentoxin-1.
[Graphical view]
PfamiPF07740. Toxin_12. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P60992-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30 
ECRYLFGGCS STSDCCKHLS CRSDWKYCAW DGTFS
Length:35
Mass (Da):4,003
Last modified:April 26, 2004 - v1
Checksum:iB9A84D9FF50AE603
GO

Mass spectrometryi

Molecular mass is 3994.59 Da from positions 1 - 35. Determined by MALDI. 1 Publication
Molecular mass is 3995.55 Da from positions 1 - 35. Determined by MALDI. 1 Publication

Cross-referencesi

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N6ONMR-A1-35[»]
ProteinModelPortaliP60992.
SMRiP60992.
ModBaseiSearch...
MobiDBiSearch...

Protein family/group databases

TCDBi8.B.5.3.3. the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ArachnoServeriAS000224. delta-theraphotoxin-Hm1a.

Family and domain databases

InterProiIPR011696. Huwentoxin-1.
[Graphical view]
PfamiPF07740. Toxin_12. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTX1_HETMC
AccessioniPrimary (citable) accession number: P60992
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: November 30, 2016
This is version 52 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

IC50 is 280 nM on Kv4.1/KCND1, whereas percentage of current inhibition are 23% on Kv2.1/KCNB1 at 100 nM, 19.7% on Kv2.2/KCNB2 at 100 nM, 39% on Kv4.2/KCND2 at 300 nM, and 43% on Kv4.3/KCND3 at 300 nM.1 Publication

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.