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Protein

Alpha-conotoxin BuIA

Gene
N/A
Organism
Conus bullatus (Bubble cone)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This peptide potently blocks numerous mammalian nAChR subtypes: alpha-6/alpha-3-beta-2 (CHRNA6/CHRNA3-CHRNB2) (IC50=0.258 nM) > alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) (IC50=1.54 nM) > alpha-3-beta-2 (CHRNA3-CHRNB2) (IC50=5.72 nM) > alpha-3-beta-4 (CHRNA3-CHRNB4)(IC50=27.7 nM) > alpha-4-beta-4 (CHRNA4-CHRNB4) (IC50=69.9 nM) > alpha-2-beta-4 (CHRNA2-CHRNB4) (IC50=121 nM) > alpha-7 (CHRNA7) (IC50=272 nM) > alpha-2-beta-2 (CHRNA2-CHRNB2) (IC50=800 nM) (PubMed:15520009). Recovery from toxin block is markedly slower for beta-4 versus beta-2 subunit-containing nAChRs (PubMed:15520009, PubMed:16964981). Residues Thr-83, Val-135 and Phe-143 in the rat beta-2 subunit and Lys-81, Ile-133 and Gln-141 in the rat beta-4 subunit are critical to off-rate differences (PubMed:16964981). Thus, this toxin represents a novel probe for distinguishing between beta-2 and beta-4 subunit-containing nAChRs (PubMed:15520009, PubMed:16964981).3 Publications

Miscellaneous

Does not inhibit alpha-4-beta-2 (CHRNA4-CHRNB2) nAChR (IC50=10.400 µM or >20 µM).2 Publications
Exists in two forms, due to cis-trans isomerization at 49-Pro-Pro-50.1 Publication

GO - Molecular functioni

Keywordsi

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

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin BuIA3 Publications
Alternative name(s):
Conotoxin Bu1.31 Publication
OrganismiConus bullatus (Bubble cone)
Taxonomic identifieri89438 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaNeogastropodaConoideaConidaeConusTextilia

Organism-specific databases

ConoServeri409 BuIA 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
Mutagenesisi47S → A: No change in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR. 4-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR. 1 Publication1
Mutagenesisi48T → A: 16-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR, 2-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR. Preferential inhibition of beta-4 subunit-containing nAChRs (over beta-2), potent block of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4), moderate block of alpha-3-beta-4 (CHRNA3-CHRNB4)and weak block of alpha-2-beta-4 (CHRNA2-CHRNB4) nAChRs and no activity on alpha-2-beta-2 (CHRNA2-CHRNB2), alpha-3-beta-2 (CHRNA3-CHRNB2), alpha-4-beta-2 (CHRNA4-CHRNB2), alpha-4-beta-4 (CHRNA4-CHRNB4), alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3), alpha-7 (CHRNA7) and alpha-9-alpha-10 (CHRNA9-CHRNA10) and alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChRs; when associated with hydroxyPro-49 (see miscellaneous). 1 Publication1
Mutagenesisi52A → S: 4-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR. 11-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR. 1 Publication1
Mutagenesisi53V → A: 37-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR. 2-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR. 1 Publication1
Mutagenesisi54L → A: 50-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR. 6-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR. 1 Publication1
Mutagenesisi55Y → A: 150-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) nAChR. 21-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) nAChR. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 16Sequence analysisAdd BLAST16
PropeptideiPRO_000003486917 – 43By similarityAdd BLAST27
PeptideiPRO_000003487044 – 56Alpha-conotoxin BuIA5 PublicationsAdd BLAST13

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi45 ↔ 51Combined sources2 Publications
Disulfide bondi46 ↔ 56Combined sources2 Publications
Modified residuei56Cysteine amide5 Publications1

Post-translational modificationi

The native globular disulfide connectivity of this toxin displays multiple conformations in solution. In contrast, the non-native ribbon isomer has a well-defined conformation. This ribbon isomer is inactive on alpha-3-beta-2 (CHRNA3-CHRNB2) and alpha-3-beta-4 (CHRNA3-CHRNB4)nAChR.1 Publication
Post-translational modification of Pro-49 into hydroxyproline [P49O] induces a 2800-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) and 6-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4).1 Publication
Post-translational modification of Pro-49 into hydroxyproline [P49O] associated with the mutation [T48A] induces a preferential inhibition of beta-4 subunit-containing nAChRs (over beta-2). On mouse/rat subunits, this mutant induces potent blocks of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4), moderate block of alpha-3-beta-4 (CHRNA3-CHRNB4), weak block of alpha-2-beta-4 (CHRNA2-CHRNB4) nAChRs and no activity on alpha-2-beta-2 (CHRNA2-CHRNB2), alpha-3-beta-2 (CHRNA3-CHRNB2), alpha-4-beta-2 (CHRNA4-CHRNB2), alpha-4-beta-4 (CHRNA4-CHRNB4), alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3), alpha-7 (CHRNA7) and alpha-9-alpha-10 (CHRNA9-CHRNA10) and alpha-1-beta-1-delta-epsilon (CHRNA1-CHRNB1-CHRND-CHRNE) nAChRs (PubMed:20739611). On human subunits, this mutant induces inhibitions on alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4) (IC50=7.4 nM), beta-4-alpha-3-beta-4-alpha-3-alpha-5 (CHRNB4-CHRNA3-CHRNB4-CHRNA3-CHRNA5) (IC50=147 nM) and alpha-3-beta-4 (CHRNA3-CHRNB4) (IC50166 nM), but no inhibition of alpha-3-beta-2 (CHRNA3-CHRNB2), alpha-4-beta-2 (CHRNA4-CHRNB2), alpha-4-beta-4 (CHRNA4-CHRNB4), alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3), beta-3-alpha-6-beta-2-alpha-4-beta-2 (CHRNB3-CHRNA6-CHRNB2-CHRNA4-CHRNB2) nAChRs (PubMed:26330550).2 Publications
Post-translational modification of Pro-50 into hydroxyproline [P50O] induces a 9-fold decrease in inhibition of alpha-6/alpha-3-beta-2-beta-3 (CHRNA6/CHRNA3-CHRNB2-CHRNB3) and a 4-fold decrease in inhibition of alpha-6/alpha-3-beta-4 (CHRNA6/CHRNA3-CHRNB4).1 Publication

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Structurei

Secondary structure

160
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP69657
SMRiP69657
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP69657

Family & Domainsi

Domaini

The cysteine framework is I (CC-C-C). Alpha4/4 pattern.Curated

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiView protein in InterPro
IPR009958 Conotoxin_a-typ
IPR018072 Conotoxin_a-typ_CS
PfamiView protein in Pfam
PF07365 Toxin_8, 1 hit
PROSITEiView protein in PROSITE
PS60014 ALPHA_CONOTOXIN, 1 hit

Sequencei

Sequence statusi: Complete.

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

P69657-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MFTVFLLVVL TTTVVSFPSD RASDGRNAAA NDKASDVVTL VLKGCCSTPP
60
CAVLYCGRRR
Length:60
Mass (Da):6,394
Last modified:March 29, 2005 - v1
Checksum:i86FF88338E0FCCE6
GO

Similar proteinsi

Cross-referencesi

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I28NMR-A44-56[»]
2NS3NMR-A44-56[»]
4EZ1X-ray2.49K/L/M/N/O44-56[»]
ProteinModelPortaliP69657
SMRiP69657
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri409 BuIA precursor

Miscellaneous databases

EvolutionaryTraceiP69657

Family and domain databases

InterProiView protein in InterPro
IPR009958 Conotoxin_a-typ
IPR018072 Conotoxin_a-typ_CS
PfamiView protein in Pfam
PF07365 Toxin_8, 1 hit
PROSITEiView protein in PROSITE
PS60014 ALPHA_CONOTOXIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCA1A_CONBU
AccessioniPrimary (citable) accession number: P69657
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: September 12, 2018
This is version 52 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
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Main funding by: National Institutes of Health

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