ID   CA16_CONEB              Reviewed;          63 AA.
AC   F2XFS9;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   31-MAY-2011, sequence version 1.
DT   25-MAY-2022, entry version 39.
DE   RecName: Full=Omega-conotoxin Eu1.6 {ECO:0000305};
DE   AltName: Full=Alpha-conopeptide Eu1.6 {ECO:0000303|PubMed:29343689};
DE   AltName: Full=Alpha-conotoxin Eb1.6 {ECO:0000312|EMBL:ADZ76589.1};
DE   Flags: Precursor;
OS   Conus eburneus (Ivory cone).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC   Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Tesselliconus.
OX   NCBI_TaxID=101300;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF AMIDATED PEPTIDE, STRUCTURE BY NMR
RP   OF 48-63, BIOASSAY, AND PHARMACEUTICAL.
RX   PubMed=29343689; DOI=10.1038/s41598-017-18479-4;
RA   Liu Z., Bartels P., Sadeghi M., Du T., Dai Q., Zhu C., Yu S., Wang S.,
RA   Dong M., Sun T., Guo J., Peng S., Jiang L., Adams D.J., Dai Q.;
RT   "A novel alpha-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels
RT   and exhibits potent analgesic activity.";
RL   Sci. Rep. 8:1004-1004(2018).
CC   -!- FUNCTION: This amidated peptide potently and teversibly inhibits
CC       Cav2.2/CACNA1B. Steady-state inactivation is enhanced at hyperpolarized
CC       membrane potentials. Also shows a weak interaction at alpha-3-beta-4/
CC       CHRNA3-CHRNB4 and alpha-7/CHRNA7 nAChRs subtypes. In vivo, exhibits a
CC       potent analgesic activity in rat partial sciatic nerve injury and
CC       chronic constriction injury models. {ECO:0000269|PubMed:29343689}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:29343689}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC       {ECO:0000305|PubMed:29343689}.
CC   -!- DOMAIN: The cysteine framework is I (CC-C-C). Alpha4/7 pattern.
CC       {ECO:0000305}.
CC   -!- PHARMACEUTICAL: Has been suggested to be a promising drug candidate for
CC       the treatment of neuropathic pain. {ECO:0000305|PubMed:29343689}.
CC   -!- MISCELLANEOUS: Shows a very weak inhibition of tetrodotoxin (TTX)-
CC       resistant sodium channels. Does not show activity at TTX-sensitive
CC       sodium channels, L- or T-type calcium channels, opioid receptors, TRPV1
CC       and KCNQ1 channels. In vivo, does not exhibit any significant side-
CC       effects for spontaneous locomotor activity, cardiac and respiratory
CC       function and drug dependence. {ECO:0000269|PubMed:29343689}.
CC   -!- SIMILARITY: Belongs to the conotoxin A superfamily. {ECO:0000305}.
CC   -!- CAUTION: A C-terminal amidation at Cys-63 is suggested by authors,
CC       despite the lack of Gly residue at position 64 which should provide the
CC       amino group (-NH2). {ECO:0000305}.
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DR   EMBL; HQ446467; ADZ76589.1; -; mRNA.
DR   AlphaFoldDB; F2XFS9; -.
DR   SMR; F2XFS9; -.
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:0005246; F:calcium 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   Acetylcholine receptor inhibiting toxin; Amidation;
KW   Calcium channel impairing toxin; Cleavage on pair of basic residues;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin; Pharmaceutical;
KW   Postsynaptic neurotoxin; Secreted; Signal; Toxin;
KW   Voltage-gated calcium channel impairing toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..47
FT                   /evidence="ECO:0000305|PubMed:29343689"
FT                   /id="PRO_0000450816"
FT   PEPTIDE         48..63
FT                   /note="Omega-conotoxin Eu1.6"
FT                   /evidence="ECO:0000305|PubMed:29343689"
FT                   /id="PRO_5003289307"
FT   REGION          51..53
FT                   /note="Ser-Xaa-Pro motif, crucial for potent interaction
FT                   with nAChR"
FT                   /evidence="ECO:0000250|UniProtKB:P56636"
FT   DISULFID        49..55
FT                   /evidence="ECO:0000305|PubMed:29343689"
FT   DISULFID        50..63
FT                   /evidence="ECO:0000305|PubMed:29343689"
SQ   SEQUENCE   63 AA;  6740 MW;  51689F66412211C8 CRC64;
     MGMRMMFTVF LLVVLATTVV SFTSDRAPDG RNAAAKAFGL ITPTVRKGCC SNPACMLKNP
     NLC