UniProtKB - P58925 (CM3A_CONPU)
Protein
Mu-conotoxin PIIIA
Gene
N/A
Organism
Conus purpurascens (Purple cone)
Status
Functioni
Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks rNav1.4/SCN4A (IC50=36-41 nM) (PubMed:10627583, PubMed:21652775). It also moderately blocks rNav1.1/SCN1A (IC50=120 nM), rNav1.2/SCN2A (IC50=620 nM), rNav1.3/SCN3A (IC50=3.2 µM), mNav1.6/SCN8A (IC50=100 nM) (PubMed:10627583, PubMed:21652775). This inhibition is reversible. The block of Nav1.1, Nav1.2, and Nav1.6 is modified when beta-subunits are coexpressed with alpha subunits. Hence, blocks of channels containing the beta-1 and beta-3 subunits are more potent (compared to channels without beta subunits), whereas blocks of channels containing the beta-2 and beta-4 are less potent (compared to channels without beta subunits). In vivo, this peptide causes flaccid paralysis in both mice and fish.6 Publications
Miscellaneous
Exists in two forms, due to cis-trans isomerization at Hyp-57. Adopts a predominately trans conformation (Probable).1 Publication
This toxin does not or only weakly blocks rNav1.5/SCN5A, rNav1.7/SCN9A (IC50=3.1-6.2 µM and >100 µM), and rNav1.8/SCN10A.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 63 | Important for activity1 Publication | 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.28.1.2 the mu-conotoxin (mu-conotoxin) family |
Names & Taxonomyi
Protein namesi | Recommended name: Mu-conotoxin PIIIA1 PublicationAlternative name(s): Mu-conotoxin P3.7 |
Organismi | Conus purpurascens (Purple cone) |
Taxonomic identifieri | 41690 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Lophotrochozoa › Mollusca › Gastropoda › Caenogastropoda › Neogastropoda › Conoidea › Conidae › Conus › Chelyconus |
Organism-specific databases
ConoServeri | 1407 PIIIA precursor |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Keywords - Cellular componenti
SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 63 | R → A: Decrease in affinity to channel. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
PropeptideiPRO_0000035053 | 20 – 49 | 1 PublicationAdd BLAST | 30 | |
PeptideiPRO_0000035054 | 50 – 71 | Mu-conotoxin PIIIA1 PublicationAdd BLAST | 22 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 50 | Pyrrolidone carboxylic acid2 Publications | 1 | |
Disulfide bondi | 53 ↔ 70 | In PIIIA-1; alternateBy similarity | ||
Disulfide bondi | 53 ↔ 65 | In PIIIA-2; alternate1 PublicationImported | ||
Disulfide bondi | 54 ↔ 71 | In PIIIA-1; alternateBy similarity | ||
Disulfide bondi | 54 ↔ 70 | In PIIIA-2; alternate1 PublicationImported | ||
Modified residuei | 57 | 4-hydroxyproline1 Publication | 1 | |
Disulfide bondi | 60 ↔ 71 | In PIIIA-2; alternate1 Publication | ||
Disulfide bondi | 60 ↔ 65 | In PIIIA-1; alternateBy similarity | ||
Modified residuei | 67 | 4-hydroxyproline1 Publication | 1 | |
Modified residuei | 71 | Cysteine amide1 Publication | 1 |
Post-translational modificationi
3D-structure of 3 disulfide-bond connectivities isomers is described (PIIIA-1 (C1-C5, C2-C6, C3-C4), PIIIA-2 (C1-C4, C2-C5, C3-C6) and PIIIA-3 (C1-C2, C3-C4, C5-C6)) (PubMed:22407516). Only PIIIA-2 contains the cysteine connectivity described as typical for native mu-conotoxins. However, PIIIA-1 is more potent than PIIIA-2, suggesting another possible disulfid connectivity. For this reason, both connectivities have been indicated in features.1 Publication
Keywords - PTMi
Amidation, Cleavage on pair of basic residues, Disulfide bond, Hydroxylation, Pyrrolidone carboxylic acidExpressioni
Tissue specificityi
Expressed by the venom duct.1 Publication
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1R9I | NMR | - | A | 50-71 | [»] | |
SMRi | P58925 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P58925 |
Family & Domainsi
Domaini
The cysteine framework is III (CC-C-C-CC). Classified in the M-4 branch, since 4 residues stand between the fourth and the fifth cysteine residues.Curated
Sequence similaritiesi
Belongs to the conotoxin M superfamily.Curated
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
P58925-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MSKLGVLLTI CLLLFPITAL PMDGDQPADR LAERMQDNIS SEEHPFEKRQ
60 70
RLCCGFPKSC RSRQCKPHRC CGR
Similar proteinsi
Cross-referencesi
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1R9I | NMR | - | A | 50-71 | [»] | |
SMRi | P58925 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protein family/group databases
TCDBi | 8.B.28.1.2 the mu-conotoxin (mu-conotoxin) family |
Protocols and materials databases
Structural Biology Knowledgebase | Search... |
Organism-specific databases
ConoServeri | 1407 PIIIA precursor |
Miscellaneous databases
EvolutionaryTracei | P58925 |
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 |
ProtoNeti | Search... |
Entry informationi
Entry namei | CM3A_CONPU | |
Accessioni | P58925Primary (citable) accession number: P58925 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 26, 2002 |
Last sequence update: | July 11, 2006 | |
Last modified: | September 12, 2018 | |
This is version 89 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-structureDocuments
- SIMILARITY comments
Index of protein domains and families - PDB cross-references
Index of Protein Data Bank (PDB) cross-references