ID CA2_CONMA Reviewed; 68 AA. AC P56636; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 3. DT 08-MAR-2011, entry version 68. DE RecName: Full=Alpha-conotoxin MII; DE Short=Alpha-MII; DE Short=CtxMII; DE AltName: Full=Alpha-conotoxin M2; DE Flags: Precursor; OS Conus magus (Magus cone) (Magician's cone snail). OC Eukaryota; Metazoa; Mollusca; Gastropoda; Caenogastropoda; OC Hypsogastropoda; Neogastropoda; Conoidea; Conidae; Conus. OX NCBI_TaxID=6492; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Venom duct; RX PubMed=14701840; DOI=10.1074/jbc.M309654200; RA Santos A.D., McIntosh J.M., Hillyard D.R., Cruz L.J., Olivera B.M.; RT "The A-superfamily of conotoxins: structural and functional RT divergence."; RL J. Biol. Chem. 279:17596-17606(2004). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 28-68. RC TISSUE=Hepatopancreas; RX MEDLINE=22206623; PubMed=12114524; DOI=10.1074/jbc.M205102200; RA McIntosh J.M., Dowell C., Watkins M., Garrett J.E., Yoshikami D., RA Olivera B.M.; RT "Alpha-conotoxin GIC from Conus geographus, a novel peptide antagonist RT of nicotinic acetylcholine receptors."; RL J. Biol. Chem. 277:33610-33615(2002). RN [3] RP PROTEIN SEQUENCE OF 49-64, SYNTHESIS OF 49-64, AMIDATION AT CYS-64, RP DISULFIDE BONDS, MASS SPECTROMETRY, AND FUNCTION. RC TISSUE=Venom; RX MEDLINE=96205934; PubMed=8631783; DOI=10.1074/jbc.271.13.7522; RA Cartier G.E., Yoshikami D., Gray W.R., Luo S., Olivera B.M., RA McIntosh J.M.; RT "A new alpha-conotoxin which targets alpha3beta2 nicotinic RT acetylcholine receptors."; RL J. Biol. Chem. 271:7522-7528(1996). RN [4] RP FUNCTION ON ALPHA-6 ACHR. RX PubMed=11044728; DOI=10.1016/S0028-3908(00)00144-1; RA Kuryatov A., Olale F., Cooper J., Choi C., Lindstrom J.; RT "Human alpha6 AChR subtypes: subunit composition, assembly, and RT pharmacological responses."; RL Neuropharmacology 39:2570-2590(2000). RN [5] RP STRUCTURE BY NMR OF 49-64, AND DISULFIDE BONDS. RX MEDLINE=98062282; PubMed=9398298; DOI=10.1021/bi971443r; RA Shon K.-J., Koerber S.C., Rivier J.E., Olivera B.M., McIntosh J.M.; RT "Three-dimensional solution structure of alpha-conotoxin MII, an RT alpha3beta2 neuronal nicotinic acetylcholine receptor-targeted RT ligand."; RL Biochemistry 36:15693-15700(1997). RN [6] RP STRUCTURE BY NMR OF 49-64, AMIDATION AT CYS-64, AND DISULFIDE BONDS. RX MEDLINE=99060038; PubMed=9843366; DOI=10.1021/bi981535w; RA Hill J.M., Oomen C.J., Miranda L.P., Bingham J.-P., Alewood P.F., RA Craik D.J.; RT "Three-dimensional solution structure of alpha-conotoxin MII by NMR RT spectroscopy: effects of solution environment on helicity."; RL Biochemistry 37:15621-15630(1998). RN [7] RP CYCLIZATION, STRUCTURE BY NMR OF 49-64, AND DISULFIDE BONDS. RX PubMed=16162671; DOI=10.1073/pnas.0504613102; RA Clark R.J., Fischer H., Dempster L., Daly N.L., Rosengren K.J., RA Nevin S.T., Meunier F.A., Adams D.J., Craik D.J.; RT "Engineering stable peptide toxins by means of backbone cyclization: RT stabilization of the alpha-conotoxin MII."; RL Proc. Natl. Acad. Sci. U.S.A. 102:13767-13772(2005). RN [8] RP MUTAGENESIS OF ASN-53; PRO-54; HIS-57; HIS-60 AND LEU-63. RX PubMed=15005608; DOI=10.1021/bi036180h; RA Everhart D., Cartier G.E., Malhotra A., Gomes A.V., McIntosh J.M., RA Luetje C.W.; RT "Determinants of potency on alpha-conotoxin MII, a peptide antagonist RT of neuronal nicotinic receptors."; RL Biochemistry 43:2732-2737(2004). CC -!- FUNCTION: Alpha-conotoxins bind to the nicotinic acetylcholine CC receptors (nAChR) and inhibit them. This toxin blocks neuronal CC mammalian nAChRs (alpha-6 or -3/beta-2 or -3 > alpha-3/beta-2 > CC alpha-3/beta-4 = alpha-4/beta-2). CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. CC -!- DOMAIN: The cysteine framework is I. CC -!- MASS SPECTROMETRY: Mass=1710.6; Method=LSI; Range=49-64; CC Source=PubMed:8631783; CC -!- MISCELLANEOUS: There are currently a number of patents describing CC the use of this peptide in therapeutic applications. CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR PIR; A59046; A59046. DR PDB; 1M2C; NMR; -; A=49-64. DR PDB; 1MII; NMR; -; A=49-64. DR PDB; 2AJW; NMR; -; A=49-65. DR PDB; 2AK0; NMR; -; A=49-65. DR PDBsum; 1M2C; -. DR PDBsum; 1MII; -. DR PDBsum; 2AJW; -. DR PDBsum; 2AK0; -. DR ProteinModelPortal; P56636; -. DR ConoServer; 8; MII precursor. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW. DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW. DR GO; GO:0009405; P:pathogenesis; IEA:UniProtKB-KW. DR GO; GO:0007268; P:synaptic transmission; IEA:UniProtKB-KW. DR InterPro; IPR009958; Conotoxin_a-typ. DR InterPro; IPR018072; Conotoxin_a-typ_CS. DR Pfam; PF07365; Toxin_8; 1. DR PROSITE; PS60014; ALPHA_CONOTOXIN; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylcholine receptor inhibitor; Amidation; KW Direct protein sequencing; Disulfide bond; Neurotoxin; KW Postsynaptic neurotoxin; Secreted; Signal; Toxin. FT SIGNAL 1 21 Potential. FT PROPEP 22 48 FT /FTId=PRO_0000034881. FT PEPTIDE 49 64 Alpha-conotoxin MII. FT /FTId=PRO_0000034882. FT MOD_RES 64 64 Cysteine amide. FT DISULFID 50 56 FT DISULFID 51 64 FT MUTAGEN 53 53 N->A: Causes a >2700-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 54 54 P->A: Causes a 700-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 57 57 H->A: Causes a 17-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 60 60 H->A: Causes a 2700-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 63 63 L->A: Causes a 15-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT TURN 50 52 FT HELIX 55 59 FT TURN 60 63 SQ SEQUENCE 68 AA; 7357 MW; FBD9AB40E6F277DF CRC64; MGMRMMFTVF LLVVLATTVV SFPSDRASDG RNAAANDKAS DVITLALKGC CSNPVCHLEH SNLCGRRR //