UniProtKB - P01523 (CM3A_CONGE)
Mu-conotoxin GIIIA
Functioni
Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks rat Nav1.4/SCN4A (IC50= 19-110 nM) (PubMed:1654319, PubMed:1326324, PubMed:10627583, PubMed:21652775, PubMed:30360356).
It also moderately blocks rNav1.1/SCN1A (Kd=260 nM), rNav1.2/SCN2A (IC50=2.7-17.8 µM), and mNav1.6/SCN8A (IC50=680 nM) (PubMed:10627583, PubMed:21652775).
The inhibition is reversible. In vivo, induces paralysis to an isolated skeletal muscle preparation from frog (cutaneous pectoralis) within a few minutes (PubMed:2410412).
5 PublicationsMiscellaneous
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 64 | Important for binding sodium channel | 1 |
GO - Molecular functioni
- sodium channel inhibitor activity Source: InterPro
- toxin activity Source: UniProtKB-KW
Keywordsi
Molecular function | Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin |
Protein family/group databases
TCDBi | 8.B.28.1.3, the mu-conotoxin (mu-conotoxin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Mu-conotoxin GIIIA2 PublicationsAlternative name(s): G3.91 Publication Geographutoxin I2 Publications Short name: GTx-I2 Publications Myotoxin I |
Organismi | Conus geographus (Geography cone) (Nubecula geographus) |
Taxonomic identifieri | 6491 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Spiralia › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Gastridium |
Organism-specific databases
ConoServeri | 1570, GIIIA [R13A] 1464, GIIIA precursor |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 52 | R → A: 5-fold decrease in activity on Nav channels (probably Nav1.4/SCN4A) from rat diaphragm. 1 Publication | 1 | |
Mutagenesisi | 53 | D → A: 2-fold decrease in activity on Nav channels (probably Nav1.4/SCN4A) from rat diaphragm. 1 Publication | 1 | |
Mutagenesisi | 53 | D → N: Increase in activity on Nav channel from eel electric membranes, and decrease in binding to rat Nav1.4/SCN4A by increasing the rate of dissociation from rat Nav1.4/SCN4A channel and decreasing the rate of association. 1 Publication | 1 | |
Mutagenesisi | 59 | K → Q: Important decrease in activity on Nav channel from eel electric membranes, and decrease in binding to rat Nav1.4/SCN4A by increasing the rate of dissociation from rat Nav1.4/SCN4A channel and potently decreasing the rate of association. 1 Publication | 1 | |
Mutagenesisi | 63 | D → A: 3.5-fold decrease in activity on Nav channels (probably Nav1.4/SCN4A) from rat diaphragm. 1 Publication | 1 | |
Mutagenesisi | 64 | R → A: 200-fold decrease in activity on Nav channels (probably Nav1.4/SCN4A) from rat diaphragm. 1 Publication | 1 | |
Mutagenesisi | 64 | R → Q: Loss of activity on Nav channel from eel electric membranes, and important decrease in binding to rat Nav1.4/SCN4A by increasing the rate of dissociation from rat Nav1.4/SCN4A channel without modifying the rate of association. 1 Publication | 1 | |
Mutagenesisi | 69 | Q → K: Increase in activity on Nav channel from eel electric membranes, and important increase in binding to rat Nav1.4/SCN4A (seemingly irreversible) by potently decreasing the rates of both dissociation and association to rat Nav1.4/SCN4A channel. 1 Publication | 1 | |
Mutagenesisi | 70 | R → A: 25-fold decrease in activity on Nav channels (probably Nav1.4/SCN4A) from rat diaphragm. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
PropeptideiPRO_0000246004 | 21 – 51 | 2 PublicationsAdd BLAST | 31 | |
PeptideiPRO_0000044493 | 52 – 73 | Mu-conotoxin GIIIA2 PublicationsAdd BLAST | 22 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 54 ↔ 66 | 4 PublicationsImported | ||
Disulfide bondi | 55 ↔ 71 | 4 PublicationsImported | ||
Modified residuei | 57 | 4-hydroxyproline; partial3 Publications | 1 | |
Modified residuei | 58 | 4-hydroxyproline; partial3 Publications | 1 | |
Disulfide bondi | 61 ↔ 72 | 4 PublicationsImported | ||
Modified residuei | 68 | 4-hydroxyproline3 Publications | 1 | |
Modified residuei | 73 | Alanine amide3 Publications | 1 |
Post-translational modificationi
Keywords - PTMi
Amidation, Cleavage on pair of basic residues, Disulfide bond, HydroxylationProteomic databases
PRIDEi | P01523 |
Expressioni
Tissue specificityi
Structurei
Secondary structure
3D structure databases
SMRi | P01523 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P01523 |
Family & Domainsi
Domaini
Sequence similaritiesi
Keywords - Domaini
SignalFamily and domain databases
InterProi | View protein in InterPro IPR004214, Conotoxin IPR008036, Conotoxin_mu-typ |
Pfami | View protein in Pfam PF02950, Conotoxin, 1 hit |
PROSITEi | View protein in PROSITE PS60013, MU_CONOTOXIN, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MMSKLGVLLT ICLLLFPLTA LPMDGDEPAN RPVERMQDNI SSEQYPLFEK
60 70
RRDCCTPPKK CKDRQCKPQR CCAGR
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB910835 mRNA Translation: BAO65603.1 |
PIRi | A01786, MXKN1 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB910835 mRNA Translation: BAO65603.1 |
PIRi | A01786, MXKN1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1TCG | NMR | - | A | 52-73 | [»] | |
1TCH | NMR | - | A | 52-73 | [»] | |
1TCJ | NMR | - | A | 52-73 | [»] | |
1TCK | NMR | - | A | 52-73 | [»] | |
SMRi | P01523 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein family/group databases
TCDBi | 8.B.28.1.3, the mu-conotoxin (mu-conotoxin) family |
Proteomic databases
PRIDEi | P01523 |
Organism-specific databases
ConoServeri | 1570, GIIIA [R13A] 1464, GIIIA precursor |
Miscellaneous databases
EvolutionaryTracei | P01523 |
Family and domain databases
InterProi | View protein in InterPro IPR004214, Conotoxin IPR008036, Conotoxin_mu-typ |
Pfami | View protein in Pfam PF02950, Conotoxin, 1 hit |
PROSITEi | View protein in PROSITE PS60013, MU_CONOTOXIN, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CM3A_CONGE | |
Accessioni | P01523Primary (citable) accession number: P01523 Secondary accession number(s): X5IG12 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 21, 1986 |
Last sequence update: | December 11, 2019 | |
Last modified: | September 29, 2021 | |
This is version 119 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Animal Toxin Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencingDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families