CA1A_CONEP
ID CA1A_CONEP Reviewed; 56 AA.
AC P56638;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 2.
DT 25-MAY-2022, entry version 81.
DE RecName: Full=Alpha-conotoxin EpI {ECO:0000303|PubMed:9624161, ECO:0000303|PubMed:9708977};
DE Flags: Precursor;
OS Conus episcopatus (Bishop's cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Darioconus.
OX NCBI_TaxID=88764;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RA Watkins M., Olivera B.M., Hillyard D.R., Mcintosh M.J., Jones R.M.;
RT "Alpha-conotoxin peptides.";
RL Patent number JP2002534996, 22-OCT-2002.
RN [2]
RP PROTEIN SEQUENCE OF 40-55, SYNTHESIS OF 40-55, DISULFIDE BONDS, SULFATION
RP AT TYR-54, AMIDATION AT CYS-55, MASS SPECTROMETRY, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=9624161; DOI=10.1074/jbc.273.25.15667;
RA Loughnan M., Bond T., Atkins A., Cuevas J., Adams D.J., Broxton N.M.,
RA Livett B.G., Down J.G., Jones A., Alewood P.F., Lewis R.J.;
RT "Alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that
RT selectively targets neuronal nicotinic acetylcholine receptors.";
RL J. Biol. Chem. 273:15667-15674(1998).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.1 ANGSTROMS) OF 40-55, AMIDATION AT CYS-55, AND
RP DISULFIDE BONDS.
RX PubMed=9708977; DOI=10.1021/bi9806549;
RA Hu S.H., Loughnan M., Miller R., Weeks C.M., Blessing R.H., Alewood P.F.,
RA Lewis R.J., Martin J.L.;
RT "The 1.1-A resolution crystal structure of [Tyr15]EpI, a novel alpha-
RT conotoxin from Conus episcopatus, solved by direct methods.";
RL Biochemistry 37:11425-11433(1998).
CC -!- FUNCTION: Alpha-conotoxins act on postsynaptic membranes, they bind to
CC the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
CC This peptide blocks mammalian nicotinic acetylcholine receptors
CC composed of alpha-3-beta-2/CHRNA3-CHRNB2 and alpha-3-beta-4/CHRNA3-
CC CHRNB4 subunits. {ECO:0000269|PubMed:9624161}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9624161}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:9624161}.
CC -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=1787.02; Method=Electrospray; Note=Without
CC sulfation.; Evidence={ECO:0000269|PubMed:9624161};
CC -!- MASS SPECTROMETRY: Mass=1867.08; Method=Electrospray; Note=With
CC sulfation.; Evidence={ECO:0000269|PubMed:9624161};
CC -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
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DR EMBL; BD261428; -; NOT_ANNOTATED_CDS; Unassigned_DNA.
DR PIR; A59042; A59042.
DR PDB; 1A0M; X-ray; 1.10 A; A/B=40-55.
DR PDB; 7N0T; NMR; -; A=40-55.
DR PDB; 7N24; NMR; -; A=40-55.
DR PDB; 7N26; NMR; -; A=40-55.
DR PDBsum; 1A0M; -.
DR PDBsum; 7N0T; -.
DR PDBsum; 7N24; -.
DR PDBsum; 7N26; -.
DR AlphaFoldDB; P56638; -.
DR SMR; P56638; -.
DR ConoServer; 405; EpI.
DR EvolutionaryTrace; P56638; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0035792; C:host cell postsynaptic membrane; IEA:UniProtKB-KW.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; 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 inhibiting toxin; Amidation;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Postsynaptic neurotoxin; Secreted; Signal; Sulfation; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..39
FT /evidence="ECO:0000269|PubMed:9624161"
FT /id="PRO_0000392692"
FT PEPTIDE 40..55
FT /note="Alpha-conotoxin EpI"
FT /evidence="ECO:0000269|PubMed:9624161"
FT /id="PRO_0000044457"
FT REGION 43..45
FT /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT with nAChR"
FT /evidence="ECO:0000250|UniProtKB:P56636"
FT MOD_RES 54
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000269|PubMed:9624161"
FT MOD_RES 55
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:9624161,
FT ECO:0000269|PubMed:9708977"
FT DISULFID 41..47
FT /evidence="ECO:0000269|PubMed:9708977,
FT ECO:0000312|PDB:1A0M"
FT DISULFID 42..55
FT /evidence="ECO:0000269|PubMed:9708977,
FT ECO:0000312|PDB:1A0M"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:1A0M"
FT HELIX 45..50
FT /evidence="ECO:0007829|PDB:1A0M"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:1A0M"
SQ SEQUENCE 56 AA; 5977 MW; B8523DFE3EF963CB CRC64;
MFTVFLLVVL ATTVVSFTSD RASDSRKDAA SGLIALTIKG CCSDPRCNMN NPDYCG
