[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Venom duct; DOI=10.1074/jbc.M309654200; PubMed=14701840 [NCBI, ExPASy, EBI, Israel, Japan] Santos A.D., McIntosh J.M., Hillyard D.R., Cruz L.J., Olivera B.M.; "The A-superfamily of conotoxins: structural and functional divergence."; J. Biol. Chem. 279:17596-17606(2004).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-68. TISSUE=Hepatopancreas; DOI=10.1074/jbc.M205102200; PubMed=12114524 [NCBI, ExPASy, EBI, Israel, Japan] McIntosh J.M., Dowell C., Watkins M., Garrett J.E., Yoshikami D., Olivera B.M.; "Alpha-conotoxin GIC from Conus geographus, a novel peptide antagonist of nicotinic acetylcholine receptors."; J. Biol. Chem. 277:33610-33615(2002).
[3]	PROTEIN SEQUENCE OF 49-64, SYNTHESIS OF 49-64, AMIDATION AT CYS-64, DISULFIDE BONDS, MASS SPECTROMETRY, AND FUNCTION. TISSUE=Venom; DOI=10.1074/jbc.271.13.7522; PubMed=8631783 [NCBI, ExPASy, EBI, Israel, Japan] Cartier G.E., Yoshikami D., Gray W.R., Luo S., Olivera B.M., McIntosh J.M.; "A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors."; J. Biol. Chem. 271:7522-7528(1996).
[4]	FUNCTION ON ALPHA-6 ACHR. DOI=10.1016/S0028-3908(00)00144-1; PubMed=11044728 [NCBI, ExPASy, EBI, Israel, Japan] Kuryatov A., Olale F., Cooper J., Choi C., Lindstrom J.; "Human alpha6 AChR subtypes: subunit composition, assembly, and pharmacological responses."; Neuropharmacology 39:2570-2590(2000).
[5]	STRUCTURE BY NMR OF 49-64, AND DISULFIDE BONDS. DOI=10.1021/bi971443r; PubMed=9398298 [NCBI, ExPASy, EBI, Israel, Japan] Shon K.-J., Koerber S.C., Rivier J.E., Olivera B.M., McIntosh J.M.; "Three-dimensional solution structure of alpha-conotoxin MII, an alpha3beta2 neuronal nicotinic acetylcholine receptor-targeted ligand."; Biochemistry 36:15693-15700(1997).
[6]	STRUCTURE BY NMR OF 49-64, AMIDATION AT CYS-64, AND DISULFIDE BONDS. DOI=10.1021/bi981535w; PubMed=9843366 [NCBI, ExPASy, EBI, Israel, Japan] Hill J.M., Oomen C.J., Miranda L.P., Bingham J.-P., Alewood P.F., Craik D.J.; "Three-dimensional solution structure of alpha-conotoxin MII by NMR spectroscopy: effects of solution environment on helicity."; Biochemistry 37:15621-15630(1998).
[7]	CYCLIZATION, STRUCTURE BY NMR OF 49-64, AND DISULFIDE BONDS. DOI=10.1073/pnas.0504613102; PubMed=16162671 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Engineering stable peptide toxins by means of backbone cyclization: stabilization of the alpha-conotoxin MII."; Proc. Natl. Acad. Sci. U.S.A. 102:13767-13772(2005).
[8]	MUTAGENESIS OF ASN-53; PRO-54; HIS-57; HIS-60 AND LEU-63. DOI=10.1021/bi036180h; PubMed=15005608 [NCBI, ExPASy, EBI, Israel, Japan] Everhart D., Cartier G.E., Malhotra A., Gomes A.V., McIntosh J.M., Luetje C.W.; "Determinants of potency on alpha-conotoxin MII, a peptide antagonist of neuronal nicotinic receptors."; Biochemistry 43:2732-2737(2004).

Comments

FUNCTION: 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).
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: Expressed by the venom duct.
MASS SPECTROMETRY: Mass=1710.6; Method=LSI; Range=49-64; Source=PubMed:8631783;.
MISCELLANEOUS: There are currently a number of patents describing the use of this peptide in therapeutic applications.
SIMILARITY: Belongs to the conotoxin A superfamily. Alpha-type family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

PIR

A59046; A59046.

3D structure databases

PDB

1M2C; NMR; -; A=49-65.	[ExPASy / RCSB / EBI]
1MII; NMR; -; A=49-65.	[ExPASy / RCSB / EBI]
2AJW; NMR; -; A=49-68.	[ExPASy / RCSB / EBI]
2AK0; NMR; -; A=49-68.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1M2C; -.
1MII; -.
2AJW; -.
2AK0; -.

ModBase

P56636.

Family and domain databases

InterPro

IPR009958; Conotoxin_a-typ.
Graphical view of domain structure.

Pfam

PF07365; Toxin_8; 1.
Pfam graphical view of domain structure.

PROSITE

PS60014; ALPHA_CONOTOXIN; 1.

Other

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Acetylcholine receptor inhibitor; Amidation; Direct protein sequencing; Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Toxin.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 21`	`21`	`Potential.`
`PROPEP`	`22 48`	`27`		`PRO_0000034881`
`PEPTIDE`	`49 64`	`16`	`Alpha-conotoxin MII.`	`PRO_0000034882`
`MOD_RES`	`64 64`		`Cysteine amide.`
`DISULFID`	`50 56`
`DISULFID`	`51 64`
`MUTAGEN`	`53 53`		`N->A: Causes a >2700-fold reduction in activity at the alpha-3/beta-2 nAChR.`
`MUTAGEN`	`54 54`		`P->A: Causes a 700-fold reduction in activity at the alpha-3/beta-2 nAChR.`
`MUTAGEN`	`57 57`		`H->A: Causes a 17-fold reduction in activity at the alpha-3/beta-2 nAChR.`
`MUTAGEN`	`60 60`		`H->A: Causes a 2700-fold reduction in activity at the alpha-3/beta-2 nAChR.`
`MUTAGEN`	`63 63`		`L->A: Causes a 15-fold reduction in activity at the alpha-3/beta-2 nAChR.`
`TURN`	`50 52`	`3`
`HELIX`	`55 59`	`5`
`TURN`	`60 63`	`4`

Sequence information

Length: 68 AA [This is the length of the unprocessed precursor]

Molecular weight: 7357 Da [This is the MW of the unprocessed precursor]

CRC64: FBD9AB40E6F277DF [This is a checksum on the sequence]

        10         20         30         40         50         60 
MGMRMMFTVF LLVVLATTVV SFPSDRASDG RNAAANDKAS DVITLALKGC CSNPVCHLEH 


SNLCGRRR

P56636 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools