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Protein

Alpha-conotoxin PeIA

Gene
N/A
Organism
Conus pergrandis (Grand cone)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Protein inferred from homologyi

Functioni

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide potently and reversibly blocks alpha-9-alpha-10 nAChR (IC50=6.9-54.9 nM), alpha-3-beta-2 (IC50=9.7-97.5 nM) and alpha-6/alpha-3-beta-2-beta-3 (IC50=11.1-17.2 nM) (PubMed:15983035, PubMed:21252227, PubMed:22914547, PubMed:23846688). Also shows a weak inhibition of alpha-6/alpha-3-beta-4 (IC50=147 nM) and alpha-3-beta-4 (IC50=480-1500 nM) (PubMed:15983035, PubMed:22914547). This synthetic toxin also inhibits N-type calcium channels (Ca2.2/CACNA1B) (IC50=1.1 nM) via the activation of the G protein-coupled GABA(B) receptor in DRG neurons (PubMed:21252227).4 Publications

Miscellaneous

This toxin shows a very weak or no inhibition on muscle alpha-1-beta-1-gamma-delta, neuronal alpha-7, and neuronal alpha-4-beta-2 nAChR.2 Publications
The mutant [A28V, S30H, V31A, N32R, E35A] is >15'000-fold more potent at inhibiting alpha-6/alpha-3-beta-2-beta-3 than alpha-3-beta-2, and is essentially inactive on all other non-alpha6-containing nAChRs including alpha-3-beta-4, alpha-4-beta-2, alpha-4-beta-4 and alpha-7 (PubMed:23846688). This mutant shows inhibition on alpha-6/alpha-3-beta-2-beta-3 (IC50=3.8 nM), beta-3-alpha-6-beta-2-alpha-4-beta-2 (IC50=6.3 nM), alpha-3-beta-4 (IC50=3.7 µM), alpha-3-beta-2 (IC50=6.1 µM), beta-4-alpha-3-beta-4-alpha-3-alpha-5 (IC50=9.2 µM), and does not inhibit alpha-4-beta-2 and alpha-4-beta-4 nAChRs (PubMed:26330550).2 Publications
The mutant [S30H, V31A, E35N] is >290-fold more potent at inhibiting alpha-6/alpha-3-beta-2-beta-3 than alpha-6/alpha-3-beta-4, demonstrating that it can discriminate between alpha-6-beta-2-beta-3 and alpha-6-beta-4 nAChRs.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei26Important residue for inhibiting alpha-3-beta-2 nAChR1 Publication1
Sitei27Important residue for inhibiting alpha-3-beta-2 nAChR1 Publication1
Sitei30Residue that is not optimum for the most potent inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 and alpha-6/alpha-3-beta-42 Publications1
Sitei31Important residue for inhibiting alpha-3-beta-2 nAChR1 Publication1
Sitei32Important residue for inhibiting alpha-3-beta-2 nAChR1 Publication1
Sitei33Important residue for inhibiting alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionAcetylcholine receptor inhibiting toxin, Calcium channel impairing toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin PeIA3 Publications
OrganismiConus pergrandis (Grand cone)
Taxonomic identifieri330676 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri5. PeIA precursor.

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi25S → A: 1.9-fold decrease in inhibition of alpha-3-beta-2 nAChR and 1.4-fold increase in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR. 1 Publication1
Mutagenesisi26H → A: 1350-fold and 65-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi26H → N: 1.4-fold decrease in inhibition of alpha-3-beta-2 nAChR and 6.4-fold increase in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR. 1 Publication1
Mutagenesisi27P → A: 580-fold and 20-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi28A → V: 4.5-fold decrease in inhibition of alpha-3-beta-2 nAChR and 2.5-fold increase in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR. 1 Publication1
Mutagenesisi30S → A: 3.3-fold and 2.4-fold increase in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi30S → H: 14-fold, 11-fold and 10-fold increase in inhibition of alpha-3-beta-2, alpha-6/alpha-3-beta-2-beta-3 and alpha-6/alpha-3-beta-4 nAChR, respectively. 1 Publication1
Mutagenesisi30S → R: 4.6-fold and 7.5-fold increase in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi31V → A: 4.4-fold and 4.6-fold increase in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively, and 2-fold decrease in inhibition of alpha-6/alpha-3-beta-4. 1 Publication1
Mutagenesisi31V → L: 5-fold increase in inhibition of alpha-3-beta-2 nAChR and 1.1-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR. 1 Publication1
Mutagenesisi31V → R: 2400-fold and 33-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi32N → A: 2.4-fold and 1.7-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi32N → E: 2.0-fold and 6.6-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi32N → K: 2400-fold and 2.4-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi32N → R: 1600-fold and 2.7-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi33H → A: 2700-fold and 420-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi34P → A: 3.3-fold decrease in inhibition of alpha-3-beta-2 nAChR and 1.3-fold increase in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR. 1 Publication1
Mutagenesisi34P → S: 1.5-fold decrease in inhibition of alpha-3-beta-2 and no change in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1
Mutagenesisi35E → A: 5.2-fold decrease in inhibition of alpha-3-beta-2 nAChR and 1.4-fold increase in inhibition of alpha-6/alpha-3-beta-2-beta-3 nAChR. 1 Publication1
Mutagenesisi35E → N: 15-fold, 2-fold and 3-fold decrease in inhibition of alpha-3-beta-2, alpha-6/alpha-3-beta-2-beta-3 and alpha-6/alpha-3-beta-4 nAChR, respectively. 1 Publication1
Mutagenesisi36L → A: 7.2-fold and 4.8-fold decrease in inhibition of alpha-3-beta-2 and alpha-6/alpha-3-beta-2-beta-3 nAChR, respectively. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_0000247850‹1 – 21By similarityAdd BLAST›21
PeptideiPRO_000024785122 – 37Alpha-conotoxin PeIA2 PublicationsAdd BLAST16

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi23 ↔ 291 PublicationImported
Disulfide bondi24 ↔ 371 PublicationImported
Modified residuei37Cysteine amideBy similarity1

Post-translational modificationi

The hydroxylation at position Pro-27 is critical, since an hydroxylation at this position decreases potency of the toxin to inhibit both alpha-3-beta-2 (1300-fold) and alpha-6/alpha-3-beta-2-beta-3 (130-fold) nAChRs.1 Publication
A non-modified residue at position Pro-34 is critical, since an hydroxylation at this position decreases potency of the toxin to inhibit alpha-3-beta-2 (1-45-fold) and increases potency to inhibit alpha-6/alpha-3-beta-2-beta-3 (1.77-fold) nAChRs.1 Publication

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Structurei

Secondary structure

138
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 25Combined sources3
Helixi27 – 30Combined sources4
Turni34 – 36Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5JMEX-ray2.34F/G/H/I22-37[»]
ProteinModelPortaliQ1L777.
SMRiQ1L777.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

The cysteine framework is I (CC-C-C). Alpha4/7 pattern.Curated

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Family and domain databases

InterProiView protein in InterPro
IPR009958. Conotoxin_a-typ.
PfamiView protein in Pfam
PF07365. Toxin_8. 1 hit.

Sequencei

Sequence statusi: Fragment.

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

Q1L777-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30 
FDGRNAAAND KASDLVALTV RGCCSHPACS VNHPELCG
Length:38
Mass (Da):3,900
Last modified:May 30, 2006 - v1
Checksum:iAE40EFB659EB0EFC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ008450 Genomic DNA. Translation: AAY57814.1.

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.

Entry informationi

Entry nameiCA1A_CONPR
AccessioniPrimary (citable) accession number: Q1L777
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: May 30, 2006
Last modified: May 10, 2017
This is version 40 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

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