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Protein

Alpha-conotoxin MII

Gene
N/A
Organism
Conus magus (Magus cone) (Magician's cone snail)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Alpha-conotoxins bind to the nicotinic acetylcholine receptors (nAChR) and inhibit them. This toxin blocks neuronal mammalian nAChRs (alpha-6 or -3/beta-2 or -3 > alpha-3/beta-2 > alpha-3/beta-4 = alpha-4/beta-2).2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

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

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin MII
Short name:
Alpha-MII
Short name:
CtxMII
Alternative name(s):
Alpha-conotoxin M2
OrganismiConus magus (Magus cone) (Magician's cone snail)
Taxonomic identifieri6492 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri8. MII precursor.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi53 – 531N → A: Causes a >2700-fold reduction in activity at the alpha-3/beta-2 nAChR. 1 Publication
Mutagenesisi54 – 541P → A: Causes a 700-fold reduction in activity at the alpha-3/beta-2 nAChR. 1 Publication
Mutagenesisi57 – 571H → A: Causes a 17-fold reduction in activity at the alpha-3/beta-2 nAChR. 1 Publication
Mutagenesisi60 – 601H → A: Causes a 2700-fold reduction in activity at the alpha-3/beta-2 nAChR. 1 Publication
Mutagenesisi63 – 631L → A: Causes a 15-fold reduction in activity at the alpha-3/beta-2 nAChR. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Propeptidei22 – 48271 PublicationPRO_0000034881Add
BLAST
Peptidei49 – 6416Alpha-conotoxin MIIPRO_0000034882Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi50 ↔ 56
Disulfide bondi51 ↔ 64
Modified residuei64 – 641Cysteine amide2 Publications

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
68
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni50 – 523Combined sources
Helixi54 – 596Combined sources
Helixi61 – 633Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M2CNMR-A49-64[»]
1MIINMR-A49-64[»]
2AJWNMR-A49-64[»]
2AK0NMR-A49-64[»]
ProteinModelPortaliP56636.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56636.

Family & Domainsi

Domaini

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

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiIPR009958. Conotoxin_a-typ.
IPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PfamiPF07365. Toxin_8. 1 hit.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P56636-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGMRMMFTVF LLVVLATTVV SFPSDRASDG RNAAANDKAS DVITLALKGC
60
CSNPVCHLEH SNLCGRRR
Length:68
Mass (Da):7,357
Last modified:September 5, 2006 - v3
Checksum:iFBD9AB40E6F277DF
GO

Mass spectrometryi

Molecular mass is 1710.6 Da from positions 49 - 64. Determined by LSI. 1 Publication

Sequence databases

PIRiA59046.

Cross-referencesi

Sequence databases

PIRiA59046.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1M2CNMR-A49-64[»]
1MIINMR-A49-64[»]
2AJWNMR-A49-64[»]
2AK0NMR-A49-64[»]
ProteinModelPortaliP56636.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri8. MII precursor.

Miscellaneous databases

EvolutionaryTraceiP56636.

Family and domain databases

InterProiIPR009958. Conotoxin_a-typ.
IPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PfamiPF07365. Toxin_8. 1 hit.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The A-superfamily of conotoxins: structural and functional divergence."
    Santos A.D., McIntosh J.M., Hillyard D.R., Cruz L.J., Olivera B.M.
    J. Biol. Chem. 279:17596-17606(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Venom duct.
  2. "Alpha-conotoxin GIC from Conus geographus, a novel peptide antagonist of nicotinic acetylcholine receptors."
    McIntosh J.M., Dowell C., Watkins M., Garrett J.E., Yoshikami D., Olivera B.M.
    J. Biol. Chem. 277:33610-33615(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-68.
    Tissue: Hepatopancreas.
  3. "A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors."
    Cartier G.E., Yoshikami D., Gray W.R., Luo S., Olivera B.M., McIntosh J.M.
    J. Biol. Chem. 271:7522-7528(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 49-64, SYNTHESIS OF 49-64, AMIDATION AT CYS-64, DISULFIDE BONDS, MASS SPECTROMETRY, FUNCTION.
    Tissue: Venom.
  4. "Human alpha6 AChR subtypes: subunit composition, assembly, and pharmacological responses."
    Kuryatov A., Olale F., Cooper J., Choi C., Lindstrom J.
    Neuropharmacology 39:2570-2590(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION ON ALPHA-6 ACHR.
  5. "Three-dimensional solution structure of alpha-conotoxin MII, an alpha3beta2 neuronal nicotinic acetylcholine receptor-targeted ligand."
    Shon K.-J., Koerber S.C., Rivier J.E., Olivera B.M., McIntosh J.M.
    Biochemistry 36:15693-15700(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 49-64, DISULFIDE BONDS.
  6. "Three-dimensional solution structure of alpha-conotoxin MII by NMR spectroscopy: effects of solution environment on helicity."
    Hill J.M., Oomen C.J., Miranda L.P., Bingham J.-P., Alewood P.F., Craik D.J.
    Biochemistry 37:15621-15630(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 49-64, AMIDATION AT CYS-64, DISULFIDE BONDS.
  7. "Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII."
    Clark R.J., Fischer H., Dempster L., Daly N.L., Rosengren K.J., Nevin S.T., Meunier F.A., Adams D.J., Craik D.J.
    Proc. Natl. Acad. Sci. U.S.A. 102:13767-13772(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: CYCLIZATION, STRUCTURE BY NMR OF 49-64, DISULFIDE BONDS.
  8. "Determinants of potency on alpha-conotoxin MII, a peptide antagonist of neuronal nicotinic receptors."
    Everhart D., Cartier G.E., Malhotra A., Gomes A.V., McIntosh J.M., Luetje C.W.
    Biochemistry 43:2732-2737(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASN-53; PRO-54; HIS-57; HIS-60 AND LEU-63.

Entry informationi

Entry nameiCA2_CONMA
AccessioniPrimary (citable) accession number: P56636
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: September 5, 2006
Last modified: July 22, 2015
This is version 87 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

There are currently a number of patents describing the use of this peptide in therapeutic applications.

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

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.