O17C_CONMA
ID O17C_CONMA Reviewed; 29 AA.
AC P37300;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Omega-conotoxin MVIIC {ECO:0000303|PubMed:7677735, ECO:0000303|PubMed:7731037};
DE Short=Omega-CgTxMVIIC {ECO:0000303|PubMed:1352986};
DE AltName: Full=SNX-230;
DE Flags: Precursor; Fragment;
OS Conus magus (Magical cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Pionoconus.
OX NCBI_TaxID=6492;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AMIDATION AT CYS-28, SYNTHESIS OF 3-28, AND
RP FUNCTION.
RX PubMed=1352986; DOI=10.1016/0896-6273(92)90221-x;
RA Hillyard D.R., Monje V.D., Mintz I.M., Bean B.P., Nadasdi L.,
RA Ramachandran J., Miljanich G.P., Azimi-Zoonooz A., McIntosh J.M.,
RA Cruz L.J., Imperial J.S., Olivera B.M.;
RT "A new Conus peptide ligand for mammalian presynaptic Ca2+ channels.";
RL Neuron 9:69-77(1992).
RN [2]
RP MUTAGENESIS OF TYR-15.
RX PubMed=7677735; DOI=10.1006/bbrc.1995.2288;
RA Kim J.-I., Takahashi M., Martin-Moutot N., Seagar M.J., Ohtake A., Sato K.;
RT "Tyr13 is essential for the binding of omega-conotoxin MVIIC to the P/Q-
RT type calcium channel.";
RL Biochem. Biophys. Res. Commun. 214:305-309(1995).
RN [3]
RP FUNCTION.
RX PubMed=10938268; DOI=10.1074/jbc.m002252200;
RA Lewis R.J., Nielsen K.J., Craik D.J., Loughnan M.L., Adams D.A.,
RA Sharpe I.A., Luchian T., Adams D.J., Bond T., Thomas L., Jones A.,
RA Matheson J.-L., Drinkwater R., Andrews P.R., Alewood P.F.;
RT "Novel omega-conotoxins from Conus catus discriminate among neuronal
RT calcium channel subtypes.";
RL J. Biol. Chem. 275:35335-35344(2000).
RN [4]
RP SYNTHESIS OF 3-28, AND ROLE OF HYDROXYLATION.
RX PubMed=18189422; DOI=10.1021/bi701934m;
RA Lopez-Vera E., Walewska A., Skalicky J.J., Olivera B.M., Bulaj G.;
RT "Role of hydroxyprolines in the in vitro oxidative folding and biological
RT activity of conotoxins.";
RL Biochemistry 47:1741-1751(2008).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=7823075; DOI=10.1136/jnnp.58.1.85;
RA Motomura M., Johnston I., Lang B., Vincent A., Newsom-Davis J.;
RT "An improved diagnostic assay for Lambert-Eaton myasthenic syndrome.";
RL J. Neurol. Neurosurg. Psych. 58:85-87(1995).
RN [6]
RP STRUCTURE BY NMR OF 3-28, AND DISULFIDE BONDS.
RX PubMed=7731037; DOI=10.1006/jmbi.1995.0205;
RA Farr-Jones S., Miljanich G.P., Nadasdi L., Ramachandran J., Basus V.J.;
RT "Solution structure of omega-conotoxin MVIIC, a high affinity ligand of P-
RT type calcium channels, using 1H NMR spectroscopy and complete relaxation
RT matrix analysis.";
RL J. Mol. Biol. 248:106-124(1995).
RN [7]
RP STRUCTURE BY NMR OF 3-28, AND DISULFIDE BONDS.
RX PubMed=10373375; DOI=10.1006/jmbi.1999.2817;
RA Nielsen K.J., Adams D., Thomas L., Bond T., Alewood P.F., Craik D.J.,
RA Lewis R.J.;
RT "Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14
RT loop splice hybrids at N and P/Q-type calcium channels.";
RL J. Mol. Biol. 289:1405-1421(1999).
CC -!- FUNCTION: Omega-conotoxins act at presynaptic membranes, they bind and
CC block voltage-gated calcium channels (Cav). This toxin preferentially
CC blocks P/Q-type calcium channels (Cav2.1/CACNA1A) (IC(50)=0.60 nM)
CC (PubMed:1352986, PubMed:10938268). Shows also an inhibition on
CC Cav2.2/CACNA1A channels (IC(50)=7.0 nM) (PubMed:10938268).
CC {ECO:0000269|PubMed:10938268, ECO:0000269|PubMed:1352986}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:1352986}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:1352986}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:10373375, ECO:0000269|PubMed:7731037}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC -!- PTM: Not hydroxylated; hydroxylation, on a synthetic hydroxylated
CC MVIIC, has a significant impact on the oxidative folding but not on the
CC biological activity. {ECO:0000269|PubMed:18189422}.
CC -!- BIOTECHNOLOGY: Could be used as a diagnostic tool for the autoimmune
CC disease Lambert-Eaton myasthenic syndrome.
CC {ECO:0000269|PubMed:7823075}.
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR EMBL; S40826; AAB22674.1; -; mRNA.
DR PIR; JH0699; JH0699.
DR PDB; 1CNN; NMR; -; A=3-28.
DR PDB; 1OMN; NMR; -; A=3-28.
DR PDB; 1V4Q; NMR; -; A=3-26.
DR PDBsum; 1CNN; -.
DR PDBsum; 1OMN; -.
DR PDBsum; 1V4Q; -.
DR AlphaFoldDB; P37300; -.
DR BMRB; P37300; -.
DR SMR; P37300; -.
DR ConoServer; 822; MVIIC precursor.
DR EvolutionaryTrace; P37300; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005246; F:calcium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR012321; Conotoxin_omega-typ_CS.
DR PROSITE; PS60004; OMEGA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Calcium channel impairing toxin; Disulfide bond;
KW Ion channel impairing toxin; Knottin; Neurotoxin; Presynaptic neurotoxin;
KW Secreted; Toxin; Voltage-gated calcium channel impairing toxin.
FT PROPEP <1..2
FT /id="PRO_0000034916"
FT PEPTIDE 3..28
FT /note="Omega-conotoxin MVIIC"
FT /evidence="ECO:0000305|PubMed:1352986"
FT /id="PRO_0000034917"
FT SITE 15
FT /note="Important for Cav2.1/CACNA1A calcium channel
FT binding"
FT /evidence="ECO:0000305|PubMed:7677735"
FT MOD_RES 28
FT /note="Cysteine amide"
FT /evidence="ECO:0000269|PubMed:1352986"
FT DISULFID 3..18
FT /evidence="ECO:0000269|PubMed:10373375,
FT ECO:0000269|PubMed:7731037, ECO:0000312|PDB:1CNN,
FT ECO:0000312|PDB:1OMN, ECO:0000312|PDB:1V4Q"
FT DISULFID 10..22
FT /evidence="ECO:0000269|PubMed:10373375,
FT ECO:0000269|PubMed:7731037, ECO:0000312|PDB:1CNN,
FT ECO:0000312|PDB:1OMN, ECO:0000312|PDB:1V4Q"
FT DISULFID 17..28
FT /evidence="ECO:0000269|PubMed:10373375,
FT ECO:0000269|PubMed:7731037, ECO:0000312|PDB:1CNN,
FT ECO:0000312|PDB:1OMN, ECO:0000312|PDB:1V4Q"
FT MUTAGEN 15
FT /note="Y->A: High decrease in activity on Cav2.1/CACNA1A."
FT /evidence="ECO:0000269|PubMed:7677735"
FT NON_TER 1
FT /evidence="ECO:0000305|PubMed:1352986"
FT TURN 12..15
FT /evidence="ECO:0007829|PDB:1CNN"
FT STRAND 17..20
FT /evidence="ECO:0007829|PDB:1CNN"
SQ SEQUENCE 29 AA; 3071 MW; AC7A68948474728A CRC64;
TRCKGKGAPC RKTMYDCCSG SCGRRGKCG
