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Protein

Delta-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

Gating modifier toxin that principally inhibits inactivation of the mammalian voltage-gated sodium channel Nav1.1/SCN1A. When tested against human Nav1.1/SCN1A-Nav1.8/SCN10A alpha subunits heterologously expressed in Xenopus oocytes, the toxin inhibits inactivation of Nav1.1 (EC(50)=38 nM), with substantially weaker effects on Nav1.2/SCN2A (EC(50)=236 nM) and Nav1.3/SCN3A (EC(50)=220 nM). The toxin inhibits several subtypes of voltage-gated potassium channels with significantly lower potency than its effects on Nav1.1/SCN1A (PubMed:27281198). It is a moderately potent blocker of Kv2.1/KCNB1, Kv2.2/KCNB2, Kv4.1/KCND1, Kv4.2/KCND2 and Kv4.3/KCND3 and has little effect on Kv1.1/KCNA1, Kv1.2/KCNA2, Kv1.3/KCNA3, Kv1.4/KCNA4, Kv1.5/KCNA5, Kv1.6/KCNA6 and Kv3.4/KCNC4 (PubMed:12065754). The binding affinity and subtype selectivity of the toxin is determined by residues within both the S1-S2 and S3-S4 loops of the domain IV voltage sensor (PubMed:27281198). Intracerebroventricular injection into mice elicits convulsions, spasms, tremors and rapid death (PubMed:12065754). When injected into mouse hindpaw, the toxin elicits an immediate and robust response to pain (PubMed:27281198). Intraplantar injection of toxin does not cause neurogenic inflammation or alter sensitivity to heat, indicative of a modality-specific effect on mechanosensitive neurons (PubMed:27281198).2 Publications

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 (and 51% at 300 nM), 39% on Kv4.2/KCND2 at 300 nM, and 43% on Kv4.3/KCND3 at 300 nM.1 Publication
Does not inhibit Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A, and Nav1.8/SCN10A at concentrations up to 1 µM.1 Publication

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

Keywordsi

Molecular functionIon channel impairing toxin, Neurotoxin, Potassium channel impairing toxin, Toxin, Voltage-gated potassium channel impairing toxin, Voltage-gated sodium 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:
Delta-theraphotoxin-Hm1a1 Publication
Short name:
Delta-TRTX-Hm1a1 Publication
Alternative name(s):
Heteroscodratoxin-11 Publication
Short name:
HmTx11 Publication
Kappa-theraphotoxin-Hm1a1 Publication
Short name:
Kappa-TRTX-Hm1a1 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

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PeptideiPRO_00000450171 – 35Delta-theraphotoxin-Hm1a2 PublicationsAdd BLAST35

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi2 ↔ 16Combined sources1 Publication
Disulfide bondi9 ↔ 21Combined sources1 Publication
Disulfide bondi15 ↔ 28Combined sources1 Publication
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

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.1 Publication

Sequence similaritiesi

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

Keywords - Domaini

Knottin

Family and domain databases

InterProiView protein in InterPro
IPR011696. Huwentoxin-1.
PfamiView protein in Pfam
PF07740. Toxin_12. 1 hit.

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

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.

Entry informationi

Entry nameiTX1A_HETMC
AccessioniPrimary (citable) accession number: P60992
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: July 5, 2017
This is version 54 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

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