UniProtKB - A0A1L1QJU3 (TP1A_HADIN)
Pi-hexatoxin-Hi1a
Functioni
This toxin potently and selectively inhibits ASIC1a (IC50=0.4 nM on rASIC1a and IC50=0.52 nM on hASIC1a), an isoform of the gene ASIC1 (PubMed:28320941).
It incompletely inhibits ASIC1a activation in a pH-independent and slowly reversible manner (Tau(off)=14.2 min for rASIC1a and 31.8 min for hASIC1a) (PubMed:28320941).
This toxin acts by binding to and stabilizing the closed state of the channel, thereby impeding the transition into a conducting state (PubMed:28320941).
This toxin may bind to the acidic pocket of ASIC1a, since mutation of a key residue of this pocket (Arg-350) abolishes the ability of the toxin to inhibit ASIC1a (PubMed:28320941).
In addition, it shows antiparasitic activities, since it moderately inhibits the larval development of the major pathogenic nematode of ruminants (H.contortus, IC50=22.9 µM) (PubMed:31213240).
In vivo, this toxin protects the brain from neuronal injury when administered up to 8 hours after stroke onset (PubMed:28320941).
2 PublicationsGO - Molecular functioni
- ion channel regulator activity Source: UniProtKB-KW
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Ion channel impairing toxin, Proton-gated sodium channel impairing toxin, Toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Pi-hexatoxin-Hi1a1 PublicationShort name: Pi-HXTX-Hi1a1 Publication Alternative name(s): Double-knot toxinCurated Short name: DkTxCurated |
Organismi | Hadronyche infensa (Fraser island funnel-web spider) (Atrax infensus) |
Taxonomic identifieri | 153481 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Hexathelidae › Hadronyche |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Pharmaceutical usei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1 – 34 | Missing : Complete loss of inhibition of rASIC1a; mutant Hi1a:C. 1 PublicationAdd BLAST | 34 | |
Mutagenesisi | 1 | N → SN: 2600-fold decrease in inhibition of rASIC1a, and inhibition become fully reversible; mutant Hi1a:N. 1 Publication | 1 | |
Mutagenesisi | 35 | P → S: Complete loss of inhibition of rASIC1a; mutant Hi1a:C. 1 Publication | 1 | |
Mutagenesisi | 36 – 75 | Missing : 2600-fold decrease in inhibition of rASIC1a, and inhibition become fully reversible; mutant Hi1a:N. 1 PublicationAdd BLAST | 40 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000440131 | 1 – 75 | Pi-hexatoxin-Hi1a1 PublicationAdd BLAST | 75 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 3 ↔ 18 | 1 PublicationImported | ||
Disulfide bondi | 10 ↔ 23 | 1 PublicationImported | ||
Disulfide bondi | 17 ↔ 33 | 1 PublicationImported | ||
Disulfide bondi | 40 ↔ 55 | 1 PublicationImported | ||
Disulfide bondi | 47 ↔ 60 | 1 PublicationImported | ||
Disulfide bondi | 54 ↔ 71 | 1 PublicationImported |
Keywords - PTMi
Disulfide bondExpressioni
Tissue specificityi
Structurei
Secondary structure
3D structure databases
SMRi | A0A1L1QJU3 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domaini
Sequence similaritiesi
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
NECIRKWLSC VDRKNDCCEG LECYKRRHSF EVCVPIPGFC LVKWKQCDGR
60 70
ERDCCAGLEC WKRSGNKSSV CAPIT
Similar proteinsi
Cross-referencesi
Web resourcesi
Biological Magnetic Resonance Data Bank |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2N8F | NMR | - | A | 1-75 | [»] | |
SMRi | A0A1L1QJU3 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Family and domain databases
MobiDBi | Search... |
Entry informationi
Entry namei | TP1A_HADIN | |
Accessioni | A0A1L1QJU3Primary (citable) accession number: A0A1L1QJU3 Secondary accession number(s): A0A1X8XKZ9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 7, 2017 |
Last sequence update: | June 7, 2017 | |
Last modified: | February 23, 2022 | |
This is version 13 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, PharmaceuticalDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families