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Protein

Alpha-conotoxin ImI

Gene
N/A
Organism
Conus imperialis (Imperial cone)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This toxin blocks mammalian neuronal nAChRs (alpha-3/beta-2 > alpha-7 > alpha-3/beta-4). Acts voltage-independently. Is highly active against the neuromuscular receptor in frog.1 Publication

Keywords - Molecular functioni

Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin ImI
Short name:
Alpha-CTx ImI
OrganismiConus imperialis (Imperial cone)
Taxonomic identifieri35631 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri93. ImI precursor.

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. other organism postsynaptic membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi9 – 91D → L: Reduction of toxicity. 1 Publication
Mutagenesisi11 – 111R → L: Reduction of toxicity. 1 Publication
Mutagenesisi15 – 151R → E: No loss of activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Propeptidei‹1 – 4›41 PublicationPRO_0000273426
Peptidei5 – 1612Alpha-conotoxin ImIPRO_0000034877Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi6 ↔ 16In Imi-ribbon form; alternate1 Publication
Disulfide bondi6 ↔ 12In Imi-globular form; alternate6 Publications
Disulfide bondi7 ↔ 16In Imi-globular form; alternate6 Publications
Disulfide bondi7 ↔ 12In Imi-ribbon form; alternate1 Publication
Modified residuei16 – 161Cysteine amide

Post-translational modificationi

Not hydroxylated; hydroxylation, on a synthetic hydroxylated ImI, improves its folding but impairs its activity against target receptors.

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.Curated

Interactioni

Protein-protein interaction databases

DIPiDIP-61127N.

Structurei

Secondary structure

1
17
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 83Combined sources
Turni10 – 123Combined sources
Helixi13 – 153Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CNLNMR-A5-16[»]
1E74NMR-A5-14[»]
1E75NMR-A5-16[»]
1E76NMR-A5-16[»]
1G2GNMR-A5-16[»]
1IM1NMR-A5-16[»]
1IMINMR-A5-16[»]
2BC7NMR-A5-16[»]
2BC8NMR-A5-16[»]
2BYPX-ray2.07F/G/H/I/J5-16[»]
2C9TX-ray2.25K/M/O/P/Q/R/S/T5-16[»]
2IGUNMR-A5-16[»]
2MOANMR-A5-16[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50983.

Family & Domainsi

Domaini

The cysteine framework is I (CC-C-C). Alpha4/3 pattern.

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Family and domain databases

InterProiIPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

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

P50983-1 [UniParc]FASTAAdd to basket

« Hide

        10 
IVRRGCCSDP RCAWRCG
Length:17
Mass (Da):1,938
Last modified:January 15, 2004 - v2
Checksum:i9590D9CEA50279CF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY159318 Genomic DNA. Translation: AAN78128.1.
PIRiA53709.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY159318 Genomic DNA. Translation: AAN78128.1.
PIRiA53709.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CNLNMR-A5-16[»]
1E74NMR-A5-14[»]
1E75NMR-A5-16[»]
1E76NMR-A5-16[»]
1G2GNMR-A5-16[»]
1IM1NMR-A5-16[»]
1IMINMR-A5-16[»]
2BC7NMR-A5-16[»]
2BC8NMR-A5-16[»]
2BYPX-ray2.07F/G/H/I/J5-16[»]
2C9TX-ray2.25K/M/O/P/Q/R/S/T5-16[»]
2IGUNMR-A5-16[»]
2MOANMR-A5-16[»]
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-61127N.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri93. ImI precursor.

Miscellaneous databases

EvolutionaryTraceiP50983.

Family and domain databases

InterProiIPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Alpha-conotoxins ImI and ImII: similar alpha 7 nicotinic receptor antagonists act at different sites."
    Ellison M.A., McIntosh J.M., Olivera B.M.
    J. Biol. Chem. 278:757-764(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SYNTHESIS OF 5-16.
    Tissue: Venom duct.
  2. "A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI."
    McIntosh J.M., Yoshikami D., Mahe E., Nielsen D.B., Rivier J.E., Gray W.R., Olivera B.M.
    J. Biol. Chem. 269:16733-16739(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 5-16, FUNCTION, SYNTHESIS OF 5-16, DISULFIDE BONDS, SUBCELLULAR LOCATION.
    Tissue: Venom.
  3. "Alpha-conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors."
    Johnson D.S., Martinez J., Elgoyhen A.B., Heinemann S.F., McIntosh J.M.
    Mol. Pharmacol. 48:194-199(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  4. "Role of hydroxyprolines in the in vitro oxidative folding and biological activity of conotoxins."
    Lopez-Vera E., Walewska A., Skalicky J.J., Olivera B.M., Bulaj G.
    Biochemistry 47:1741-1751(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 5-16, ROLE OF HYDROXYLATION.
  5. "Modulation of conotoxin structure and function is achieved through a multienzyme complex in the venom glands of cone snails."
    Safavi-Hemami H., Gorasia D.G., Steiner A.M., Williamson N.A., Karas J.A., Gajewiak J., Olivera B.M., Bulaj G., Purcell A.W.
    J. Biol. Chem. 287:34288-34303(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS (RIBBON FORM), FOLDING.
    Tissue: Venom.
  6. "NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins specific for neuronal nicotinic acetylcholine receptors."
    Rogers J.P., Luginbuehl P., Shen G.S., McCabe R.T., Stevens R.C., Wemmer D.E.
    Biochemistry 38:3874-3882(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
  7. "Solution structure of alpha-conotoxin ImI determined by two-dimensional NMR spectroscopy."
    Gouda H., Hirono S.
    Biochim. Biophys. Acta 1431:384-394(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
  8. "NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors."
    Maslennikov I.V., Shenkarev Z.O., Zhmak M.N., Ivanov V.T., Methfessel C., Tsetlin V.I., Arseniev A.S.
    FEBS Lett. 444:275-280(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
  9. "Minimal conformation of the alpha-conotoxin ImI for the alpha7 neuronal nicotinic acetylcholine receptor recognition: correlated CD, NMR and binding studies."
    Lamthanh H., Jegou-Matheron C., Servent D., Menez A., Lancelin J.-M.
    FEBS Lett. 454:293-298(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
  10. "Solution structure of alpha-conotoxin ImI by 1H nuclear magnetic resonance."
    Gehrmann J., Daly N.L., Alewood P.F., Craik D.J.
    J. Med. Chem. 42:2364-2372(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 5-16, DISULFIDE BONDS.
  11. "Structure-activity relationships in a peptidic alpha7 nicotinic acetylcholine receptor antagonist."
    Rogers J.P., Luginbuhl P., Pemberton K., Harty P., Wemmer D.E., Stevens R.C.
    J. Mol. Biol. 304:911-926(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASP-9; ARG-11 AND ARG-15, STRUCTURE BY NMR OF 5-16 OF THESE THREE MUTANTS, DISULFIDE BONDS.

Entry informationi

Entry nameiCA1_CONIM
AccessioniPrimary (citable) accession number: P50983
Secondary accession number(s): Q8I6R4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 30, 1996
Last sequence update: January 15, 2004
Last modified: March 3, 2015
This is version 91 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

This toxin is a substrate for a multienzyme complex that regulates its folding and assembly. This complex is composed of protein-disulfide isomerase (PDI), peptidyl-prolyl cis-trans isomerase (PPI) and immunoglobulin-binding protein (BiP). PDI catalyzes the oxidation and reduction of disulfide bonds. Oxidative folding rates are further increased in the presence of PPI with the maximum effect observed in the presence of both enzymes. In contrast, BiP is only observed to assist folding in the presence of microsomes, suggesting that additional cofactors are involved. This toxin has been observed in the venom as globular (disulfide pattern C1-C3 and C2-C4) and ribbon form (C1-C4 and C2-C3).1 Publication
Has no effect on nAChRs composed of alpha-2/beta-2, alpha-3/beta-2, alpha-4/beta-2, alpha-2/beta-4, alpha-3/beta-4, or alpha-4/beta-4 subunits.

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

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

External Data

Dasty 3

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 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.