CA1A_CONER
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}.
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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
