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Protein

Mu-conotoxin PIIIA

Gene
N/A
Organism
Conus purpurascens (Purple cone)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks rNav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.2/SCN2A, rNav1.3/SCN3A, mNav1.6/SCN8A, and h/rNav1.7/SCN9A. This inhibition is reversible. The block of SCN1A, SCN2A, and SCN8A 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). This peptide causes flaccid paralysis in both mice and fish.5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei63Important for activity1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Mu-conotoxin PIIIA
Alternative name(s):
Mu-conotoxin P3.7
OrganismiConus purpurascens (Purple cone)
Taxonomic identifieri41690 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri1407. PIIIA precursor.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi63R → A: Decrease in affinity to channel. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000003505320 – 49Add BLAST30
PeptideiPRO_000003505450 – 71Mu-conotoxin PIIIAAdd BLAST22

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei50Pyrrolidone carboxylic acid1
Disulfide bondi53 ↔ 70In PIIIA-1; alternateBy similarity
Disulfide bondi53 ↔ 65In PIIIA-2; alternateCurated
Disulfide bondi54 ↔ 71In PIIIA-1; alternateBy similarity
Disulfide bondi54 ↔ 70In PIIIA-2; alternateCurated
Modified residuei574-hydroxyproline1 Publication1
Disulfide bondi60 ↔ 71In PIIIA-2; alternateCurated
Disulfide bondi60 ↔ 65In PIIIA-1; alternateBy similarity
Modified residuei674-hydroxyproline1 Publication1
Modified residuei71Cysteine amide1 Publication1

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 acid

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

173
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni52 – 55Combined sources4
Helixi59 – 61Combined sources3
Turni63 – 67Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R9INMR-A50-71[»]
SMRiP58925.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP58925.

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.

Sequence similaritiesi

Belongs to the conotoxin M superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiIPR004214. Conotoxin.
IPR008036. Conotoxin_mu-typ.
[Graphical view]
PfamiPF02950. Conotoxin. 1 hit.
[Graphical view]
PROSITEiPS60013. MU_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P58925-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKLGVLLTI CLLLFPITAL PMDGDQPADR LAERMQDNIS SEEHPFEKRQ
60 70
RLCCGFPKSC RSRQCKPHRC CGR
Length:73
Mass (Da):8,334
Last modified:July 11, 2006 - v2
Checksum:i1AF52E344F6EE982
GO

Cross-referencesi

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1R9INMR-A50-71[»]
SMRiP58925.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri1407. PIIIA precursor.

Miscellaneous databases

EvolutionaryTraceiP58925.

Family and domain databases

InterProiIPR004214. Conotoxin.
IPR008036. Conotoxin_mu-typ.
[Graphical view]
PfamiPF02950. Conotoxin. 1 hit.
[Graphical view]
PROSITEiPS60013. MU_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCM3A_CONPU
AccessioniPrimary (citable) accession number: P58925
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 26, 2002
Last sequence update: July 11, 2006
Last modified: November 2, 2016
This is version 83 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

Exists in two forms, due to cis-trans isomerization at Hyp-11. Adopts a predominately trans conformation (Probable).Curated
Does not block rNav1.5/SCN5A, rNav1.7/SCN9A, and rNav1.8/SCN10A.1 Publication

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.