ID CXA2_CONMA STANDARD; PRT; 68 AA. AC P56636; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 05-SEP-2006, sequence version 3. DT 05-SEP-2006, entry version 43. DE Alpha-conotoxin MII precursor (CtxMII) (M2). OS Conus magus (Magus cone) (Magician's cone snail). OC Eukaryota; Metazoa; Mollusca; Gastropoda; Orthogastropoda; OC Apogastropoda; Caenogastropoda; Sorbeoconcha; Hypsogastropoda; OC 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. In contrast to other alpha- CC conotoxins, this peptide has no detectable activity at the muscle CC subtype of receptor, but instead, it potently targets neuronal CC nAChR. Blocks mammalian nAChR composed of alpha3beta2 subunits and CC composed of alpha6beta2beta3 subunits. Has an activity 2 to 4 CC orders of magnitude less potent on other nAChR subunit CC combinations. CC -!- SUBCELLULAR LOCATION: Secreted protein. CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. CC -!- MASS SPECTROMETRY: MW=1710.6; METHOD=LSI; RANGE=49-64; NOTE=Ref.3. 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. Alpha-type CC family. 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; @=49-64. DR PDB; 1MII; NMR; A=49-64. DR PDB; 2AJW; NMR; A=49-64. DR PDB; 2AK0; NMR; A=49-64. DR InterPro; IPR013007; Alpha_conotoxin. DR InterPro; IPR009958; Toxin_8. DR Pfam; PF07365; Toxin_8; 1. DR PROSITE; PS60014; ALPHA_CONOTOXIN; 1. KW 3D-structure; Acetylcholine receptor inhibitor; Amidation; KW Direct protein sequencing; Neurotoxin; Postsynaptic neurotoxin; KW 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 (G-65 provides amide FT group). 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 30 31 FT STRAND 32 32 FT HELIX 33 38 FT TURN 39 39 FT HELIX 40 42 SQ SEQUENCE 68 AA; 7357 MW; FBD9AB40E6F277DF CRC64; MGMRMMFTVF LLVVLATTVV SFPSDRASDG RNAAANDKAS DVITLALKGC CSNPVCHLEH SNLCGRRR //