UniProtKB - D2Y1Y2 (H3A04_CYRHA)
Protein
Hainantoxin-III 4
Gene
N/A
Organism
Cyriopagopus hainanus (Chinese bird spider) (Haplopelma hainanum)
Status
Functioni
Selective antagonist of neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (IC50=1270 nM on Nav1.1/SCN1A, 270 nM on Nav1.2/SCN2A, 491 nM on Nav1.3/SCN3A and 232 nM on Nav1.7/SCN9A). This toxin suppress Nav1.7 current amplitude without significantly altering the activation, inactivation, and repriming kinetics. Short extreme depolarizations partially activate the toxin-bound channel, indicating voltage-dependent inhibition of this toxin. This toxin increases the deactivation of the Nav1.7 current after extreme depolarizations. The toxin-Nav1.7 complex is gradually dissociated upon prolonged strong depolarizations in a voltage-dependent manner, and the unbound toxin rebinds to Nav1.7 after a long repolarization. Moreover, analysis of chimeric channels showed that the DIIS3-S4 linker is critical for toxin binding to Nav1.7. These data are consistent with this toxin interacting with Nav1.7 site 4 and trapping the domain II voltage sensor in the closed state.1 Publication
Miscellaneous
Has no activity on Nav1.4, Nav1.5, Nav1.8 and Nav1.9 sodium and calcium currents.2 Publications
Caution
Several genes are coding for this toxin for which the structure by NMR has been determined. The cross-references to PDB and additional information can be found in entry AC D2Y1X9.Curated
GO - Molecular functioni
- ion channel inhibitor activity Source: InterPro
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Ion channel impairing toxin, Neurotoxin, Presynaptic neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Hainantoxin-III 42 PublicationsShort name: HnTx-III2 Publications Alternative name(s): Hainantoxin-3.4 Mu-theraphotoxin-Hhn2a Short name: Mu-TRTX-Hhn2a Peptide F7-18.76 |
Organismi | Cyriopagopus hainanus (Chinese bird spider) (Haplopelma hainanum) |
Taxonomic identifieri | 209901 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Chelicerata › Arachnida › Araneae › Mygalomorphae › Theraphosidae › Haplopelma |
Organism-specific databases
ArachnoServeri | AS000339 mu-theraphotoxin-Hhn2a |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Other locations
- other organism presynaptic membrane Source: UniProtKB-KW
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
PropeptideiPRO_0000400510 | 22 – 48 | 2 PublicationsAdd BLAST | 27 | |
PeptideiPRO_0000400511 | 49 – 81 | Hainantoxin-III 42 PublicationsAdd BLAST | 33 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 50 ↔ 65 | 2 Publications | ||
Disulfide bondi | 57 ↔ 70 | 2 Publications | ||
Disulfide bondi | 64 ↔ 77 | 2 Publications | ||
Modified residuei | 81 | Leucine amide1 Publication | 1 |
Keywords - PTMi
Amidation, Disulfide bondExpressioni
Tissue specificityi
Expressed by the venom gland.2 Publications
Interactioni
Subunit structurei
Monomer.1 Publication
Family & Domainsi
Domaini
The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.1 Publication
Sequence similaritiesi
Keywords - Domaini
Knottin, SignalFamily and domain databases
InterProi | View protein in InterPro IPR011696 Huwentoxin-1 IPR013140 Huwentoxin_CS1 |
Pfami | View protein in Pfam PF07740 Toxin_12, 1 hit |
PROSITEi | View protein in PROSITE PS60021 HWTX_1, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
D2Y1Y2-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKASMYLALA GLVLLFVVGY ASESEEKEFP RELLSKIFAV DDFKGKERGC
60 70 80
KGFGDSCTPG KNECCPNYAC SSKHKWCKVY LGK
Mass spectrometryi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | GU292859 mRNA Translation: ADB56675.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | GU292859 mRNA Translation: ADB56675.1 |
3D structure databases
SMRi | D2Y1Y2 |
ModBasei | Search... |
MobiDBi | Search... |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Organism-specific databases
ArachnoServeri | AS000339 mu-theraphotoxin-Hhn2a |
Family and domain databases
InterProi | View protein in InterPro IPR011696 Huwentoxin-1 IPR013140 Huwentoxin_CS1 |
Pfami | View protein in Pfam PF07740 Toxin_12, 1 hit |
PROSITEi | View protein in PROSITE PS60021 HWTX_1, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | H3A04_CYRHA | |
Accessioni | D2Y1Y2Primary (citable) accession number: D2Y1Y2 Secondary accession number(s): P83464 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 2, 2010 |
Last sequence update: | March 2, 2010 | |
Last modified: | December 5, 2018 | |
This is version 26 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
Direct protein sequencingDocuments
- SIMILARITY comments
Index of protein domains and families