UniProtKB - Q7YXD3 (SCX8_ANDMA)
Alpha-toxin Amm8
Functioni
Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission (PubMed:12911331).
The toxin principally slows the inactivation process of TTX-sensitive sodium channels (PubMed:23685008).
It discriminates neuronal versus muscular sodium channel, as it is more potent on rat brain Nav1.2/SCN2A (EC(50)=29 nM) than on rat skeletal muscle Nav1.4/SCN4A (EC(50)=416 nM) (PubMed:12911331).
It also shows a weak activity on Nav1.7/SCN9A (EC(50)=1.76 µM) (PubMed:23685008).
In vivo, the toxin produces pain hypersensibility to mechanical and thermal stimuli.(PubMed:23685008).
It also exhibits potent analgesic activity (when injected intraperitoneally), increasing hot plate and tail flick withdrawal latencies in a dose-dependent fashion (PubMed:20619318).
This paradoxical analgesic action, is significantly suppressed by opioid receptor antagonists, suggesting a pain-induced analgesia mechanism that involves an endogenous opioid system (PubMed:20619318).
This led to hypothesis that pain relief induced by peripheral administration of Amm VIII may result from sensitization of primary afferent neurons and subsequent activation of an opioid-dependent noxious inhibitory control (PubMed:20619318).
3 PublicationsMiscellaneous
GO - Molecular functioni
- sodium channel inhibitor activity Source: InterPro
- toxin activity Source: UniProtKB-KW
GO - Biological processi
- defense response Source: InterPro
- modulation by symbiont of host nervous system process Source: InterPro
Keywordsi
Molecular function | Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin |
Names & Taxonomyi
Protein namesi | Recommended name: Alpha-toxin Amm8CuratedAlternative name(s): Alpha-anatoxin Amm VIII1 Publication Short name: Amm VIII3 Publications Short name: AmmVIII1 Publication Neurotoxin 8 P4 |
Organismi | Androctonus mauritanicus mauritanicus (Scorpion) |
Taxonomic identifieri | 6860 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Androctonus › |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Toxic dosei
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | 1 PublicationAdd BLAST | 19 | |
ChainiPRO_0000035232 | 20 – 84 | Alpha-toxin Amm81 PublicationAdd BLAST | 65 | |
PropeptideiPRO_0000035233 | 85 | Removed by a carboxypeptidase | 1 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 31 ↔ 82 | PROSITE-ProRule annotation | ||
Disulfide bondi | 35 ↔ 55 | PROSITE-ProRule annotation | ||
Disulfide bondi | 41 ↔ 65 | PROSITE-ProRule annotation | ||
Disulfide bondi | 45 ↔ 67 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bondExpressioni
Tissue specificityi
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 21 – 83 | LCN-type CS-alpha/betaPROSITE-ProRule annotationAdd BLAST | 63 |
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalFamily and domain databases
CDDi | cd00107, Knot1, 1 hit |
Gene3Di | 3.30.30.10, 1 hit |
InterProi | View protein in InterPro IPR044062, LCN-type_CS_alpha_beta_dom IPR003614, Scorpion_toxin-like IPR036574, Scorpion_toxin-like_sf IPR018218, Scorpion_toxinL IPR002061, Scorpion_toxinL/defensin |
Pfami | View protein in Pfam PF00537, Toxin_3, 1 hit |
PRINTSi | PR00285, SCORPNTOXIN |
SMARTi | View protein in SMART SM00505, Knot1, 1 hit |
SUPFAMi | SSF57095, SSF57095, 1 hit |
PROSITEi | View protein in PROSITE PS51863, LCN_CSAB, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MNYLVMISLA LLFMTGVESL KDGYIVNDIN CTYFCGRNAY CNELCIKLKG
60 70 80
ESGYCQWASP YGNSCYCYKL PDHVRTKGPG RCNDR
Mass spectrometryi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ496808 mRNA Translation: CAD43222.1 AM159181 Genomic DNA Translation: CAJ43744.1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ496808 mRNA Translation: CAD43222.1 AM159181 Genomic DNA Translation: CAJ43744.1 |
3D structure databases
AlphaFoldDBi | Q7YXD3 |
SMRi | Q7YXD3 |
ModBasei | Search... |
Family and domain databases
CDDi | cd00107, Knot1, 1 hit |
Gene3Di | 3.30.30.10, 1 hit |
InterProi | View protein in InterPro IPR044062, LCN-type_CS_alpha_beta_dom IPR003614, Scorpion_toxin-like IPR036574, Scorpion_toxin-like_sf IPR018218, Scorpion_toxinL IPR002061, Scorpion_toxinL/defensin |
Pfami | View protein in Pfam PF00537, Toxin_3, 1 hit |
PRINTSi | PR00285, SCORPNTOXIN |
SMARTi | View protein in SMART SM00505, Knot1, 1 hit |
SUPFAMi | SSF57095, SSF57095, 1 hit |
PROSITEi | View protein in PROSITE PS51863, LCN_CSAB, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SCX8_ANDMA | |
Accessioni | Q7YXD3Primary (citable) accession number: Q7YXD3 Secondary accession number(s): Q2YHM2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 16, 2004 |
Last sequence update: | October 1, 2003 | |
Last modified: | May 25, 2022 | |
This is version 66 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