ID CXA2_CONMA STANDARD; PRT; 41 AA. AC P56636; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2004, sequence version 2. DT 30-MAY-2006, entry version 42. DE Alpha-conotoxin MII precursor (CtxMII) (M2) (Fragment). OS Conus magus (Magus cone). 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 [GENOMIC DNA]. 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 [2] RP PROTEIN SEQUENCE OF 22-37, SYNTHESIS OF 22-37, 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 [3] 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 [4] RP STRUCTURE BY NMR OF 22-37, 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 [5] RP STRUCTURE BY NMR OF 22-37, 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 [6] RP CYCLIZATION, STRUCTURE BY NMR OF 22-38, 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 [7] RP MUTAGENESIS OF ASN-26; PRO-27; HIS-30; HIS-33 AND LEU-36. 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 alpha-3/beta-2 subunits CC and composed of alpha-6/beta-2/beta-3 subunits. Has an activity 2 CC to 4 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 -!- 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; @=22-37. DR PDB; 1MII; NMR; A=22-37. DR PDB; 2AJW; NMR; A=22-38. DR PDB; 2AK0; NMR; A=22-38. 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 ? Potential. FT PROPEP ? 21 FT /FTId=PRO_0000034881. FT PEPTIDE 22 37 Alpha-conotoxin MII. FT /FTId=PRO_0000034882. FT MOD_RES 37 37 Cysteine amide (G-38 provides amide FT group). FT DISULFID 23 29 FT DISULFID 24 37 FT MUTAGEN 26 26 N->A: Causes a >2700-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 27 27 P->A: Causes a 700-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 30 30 H->A: Causes a 17-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 33 33 H->A: Causes a 2700-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT MUTAGEN 36 36 L->A: Causes a 15-fold reduction in FT activity at the alpha-3/beta-2 nAChR. FT NON_TER 1 1 FT TURN 3 4 FT STRAND 5 5 FT HELIX 6 11 FT TURN 12 12 FT HELIX 13 15 SQ SEQUENCE 41 AA; 4354 MW; 6D2AF23E5F5A036D CRC64; SDGRNAAAND KASDVITLAL KGCCSNPVCH LEHSNLCGRR R //