ID CA1A_CONER Reviewed; 62 AA. AC P50982; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 23-MAR-2010, sequence version 2. DT 25-MAY-2022, entry version 80. DE RecName: Full=Alpha-conotoxin EI {ECO:0000303|PubMed:7578057}; DE Flags: Precursor; OS Conus ermineus (Agate cone) (Chelyconus ermineus). OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda; OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Chelyconus. OX NCBI_TaxID=55423; RN [1] RP NUCLEOTIDE SEQUENCE. RA Olivera B.M., Layer R.T., Watkins M., Hillyard D.R., Mcintosh M.J., RA Jones R.M., Schoenfeld R.; RT "Alpha conotoxin peptides."; RL Patent number JP2003525582, 02-SEP-2003. RN [2] RP PROTEIN SEQUENCE OF 44-61, FUNCTION, SYNTHESIS, SUBCELLULAR LOCATION, RP DISULFIDE BONDS, HYDROXYLATION AT PRO-46, AMIDATION AT CYS-61, AND MASS RP SPECTROMETRY. RC TISSUE=Venom; RX PubMed=7578057; DOI=10.1021/bi00044a030; RA Martinez J.S., Olivera B.M., Gray W.R., Craig A.G., Groebe D.R., RA Abramson S.N., McIntosh J.M.; RT "Alpha-conotoxin EI, a new nicotinic acetylcholine receptor antagonist with RT novel selectivity."; RL Biochemistry 34:14519-14526(1995). RN [3] RP PROTEIN SEQUENCE OF 44-61, IDENTIFICATION BY MASS SPECTROMETRY, AND RP SUBCELLULAR LOCATION. RC TISSUE=Venom; RX PubMed=28238803; DOI=10.1016/j.toxicon.2017.02.023; RA Echterbille J., Gilles N., Araoz R., Mourier G., Amar M., Servent D., RA De Pauw E., Quinton L.; RT "Discovery and characterization of EIIB, a new alpha-conotoxin from Conus RT ermineus venom by nAChRs affinity capture monitored by MALDI-TOF/TOF mass RT spectrometry."; RL Toxicon 130:1-10(2017). RN [4] RP FUNCTION. RX PubMed=17635581; DOI=10.1111/j.1742-4658.2007.05931.x; RA Lopez-Vera E., Aguilar M.B., Schiavon E., Marinzi C., Ortiz E., RA Restano Cassulini R., Batista C.V.F., Possani L.D., RA Heimer de la Cotera E.P., Peri F., Becerril B., Wanke E.; RT "Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share RT high-affinity potentiation and low-affinity inhibition of nicotinic RT acetylcholine receptors."; RL FEBS J. 274:3972-3985(2007). RN [5] RP FUNCTION. RX PubMed=25466886; DOI=10.1096/fj.14-262733; RA Heghinian M.D., Mejia M., Adams D.J., Godenschwege T.A., Mari F.; RT "Inhibition of cholinergic pathways in Drosophila melanogaster by alpha- RT conotoxins."; RL FASEB J. 29:1011-1018(2015). RN [6] RP FUNCTION. RX PubMed=32245200; DOI=10.3390/toxins12030197; RA Rybin M.J., O'Brien H., Ramiro I.B.L., Azam L., McIntosh J.M., RA Olivera B.M., Safavi-Hemami H., Yoshikami D.; RT "AlphaM-conotoxin MIIIJ blocks nicotinic acetylcholine receptors at RT neuromuscular junctions of frog and fish."; RL Toxins 12:0-0(2020). RN [7] RP STRUCTURE BY NMR OF 44-61, HYDROXYLATION AT PRO-46, AMIDATION AT CYS-61, RP AND DISULFIDE BONDS. RX PubMed=11641403; DOI=10.1074/jbc.m107798200; RA Park K.-H., Suk J.-E., Jacobsen R., Gray W.R., McIntosh J.M., Han K.-H.; RT "Solution conformation of alpha-conotoxin EI, a neuromuscular toxin RT specific for the alpha 1/delta subunit interface of torpedo nicotinic RT acetylcholine receptor."; RL J. Biol. Chem. 276:49028-49033(2001). CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. CC Probable competitive antagonist of fish muscle acetylcholine receptor CC (PubMed:32245200). Inhibits postsynaptic nicotinic acetylcholine CC receptors (nAChRs) from zebrafish (IC(50)=58-100 nM) (PubMed:32245200). CC Blocks mammalian nAChR composed of alpha-1/gamma and alpha-1/delta CC subunits. Blocks central nervous system nAChR composed of alpha-4-beta- CC 2/CHRNA4-CHRNB2 subunits and peripheral nervous system nAChR composed CC of alpha-3-beta-4/CHRNA3-CHRNB4 subunits. Low toxin concentrations CC potentiate currents in muscle nAChR composed of alpha-1-beta-1-gamma- CC delta (CHRNA1-CHRNB1-CHRNG-CHRND) subunits and central nervous system CC nAChR composed of alpha-4-beta-2/CHRNA4-CHRNB2 subunits, but not CC peripheral nervous system nAChR composed of alpha-3-beta-4 subunits. CC Also exhibits inhibition of D.melanogaster alpha-7/CHRNA7 nAChRs CC (PubMed:25466886). Has possibly a distinct nAChR binding mode from CC other alpha-conotoxins, due to a different three residue motif (lacks CC the Ser-Xaa-Pro motif) (By similarity). {ECO:0000250|UniProtKB:Q2I2R8, CC ECO:0000269|PubMed:17635581, ECO:0000269|PubMed:25466886, CC ECO:0000269|PubMed:32245200, ECO:0000269|PubMed:7578057}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28238803, CC ECO:0000269|PubMed:7578057}. CC -!- TISSUE SPECIFICITY: Expressed by the venom duct. CC {ECO:0000305|PubMed:28238803, ECO:0000305|PubMed:7578057}. CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern. CC {ECO:0000305}. CC -!- MASS SPECTROMETRY: Mass=2092.9; Method=LSI; CC Evidence={ECO:0000269|PubMed:7578057}; CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}. 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 EMBL; BD394990; -; NOT_ANNOTATED_CDS; Unassigned_DNA. DR PIR; A58589; A58589. DR PDB; 1K64; NMR; -; A=44-61. DR PDBsum; 1K64; -. DR AlphaFoldDB; P50982; -. DR SMR; P50982; -. DR ConoServer; 50; EI. DR EvolutionaryTrace; P50982; -. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW. DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IDA:UniProtKB. DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW. DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB. DR GO; GO:0044504; P:modulation of receptor activity in another organism; IDA:UniProtKB. 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 inhibiting toxin; Amidation; KW Direct protein sequencing; Disulfide bond; Hydroxylation; KW Ion channel impairing toxin; Neurotoxin; Postsynaptic neurotoxin; Secreted; KW Signal; Toxin. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT PROPEP 17..43 FT /evidence="ECO:0000269|PubMed:7578057" FT /id="PRO_0000392693" FT PEPTIDE 44..61 FT /note="Alpha-conotoxin EI" FT /evidence="ECO:0000269|PubMed:7578057" FT /id="PRO_0000044458" FT REGION 49..51 FT /note="Lacks the Ser-Xaa-Pro motif that is crucial for FT potent interaction with nAChR" FT /evidence="ECO:0000305" FT MOD_RES 46 FT /note="4-hydroxyproline" FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0000269|PubMed:7578057" FT MOD_RES 61 FT /note="Cysteine amide" FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0000269|PubMed:7578057" FT DISULFID 47..53 FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0000269|PubMed:7578057, ECO:0000312|PDB:1K64" FT DISULFID 48..61 FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0000269|PubMed:7578057, ECO:0000312|PDB:1K64" FT HELIX 46..49 FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0007829|PDB:1K64" FT HELIX 52..55 FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0007829|PDB:1K64" FT HELIX 58..60 FT /evidence="ECO:0000269|PubMed:11641403, FT ECO:0007829|PDB:1K64" SQ SEQUENCE 62 AA; 6637 MW; 7D3E9D3F46B52186 CRC64; MFTVFLLVVL ATTVGSFTLD RASDGRDAAA NDKASDLIAL TARRDPCCYH PTCNMSNPQI CG //