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Protein

Alpha-conotoxin PeIA

Gene
N/A
Organism
Conus pergrandis (Grand cone)
Status
Reviewed-Annotation score: -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

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 lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaNeogastropodaConoideaConidaeConusEmbrikena

Organism-specific databases

ConoServeri5 PeIA precursor

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 21CuratedAdd 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 amide1 Publication1

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

3D structure databases

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

Cross-referencesi

Sequence databases

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

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...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri5 PeIA precursor

Family and domain databases

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

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: October 10, 2018
This is version 45 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. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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