O16A_CONMB
ID O16A_CONMB Reviewed; 76 AA.
AC A0A384E129;
DT 13-FEB-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-FEB-2019, sequence version 2.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=Omega-conotoxin MoVIA {ECO:0000303|PubMed:30194442};
DE Contains:
DE RecName: Full=Omega-conotoxin MoVIB {ECO:0000303|PubMed:30194442};
DE Flags: Precursor;
OS Conus moncuri (Sea snail).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Embrikena.
OX NCBI_TaxID=2496636;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 46-75 AND 46-76, FUNCTION,
RP STRUCTURE BY NMR OF 46-75 (MOVIB), HYDROXYLATION AT PRO-49 AND PRO-55,
RP DISULFIDE BOND, SUBCELLULAR LOCATION, SYNTHESIS OF 46-75 AND 46-76, AND
RP MUTAGENESIS OF ARG-58.
RC TISSUE=Venom, and Venom duct;
RX PubMed=30194442; DOI=10.1038/s41598-018-31245-4;
RA Sousa S.R., McArthur J.R., Brust A., Bhola R.F., Rosengren K.J.,
RA Ragnarsson L., Dutertre S., Alewood P.F., Christie M.J., Adams D.J.,
RA Vetter I., Lewis R.J.;
RT "Novel analgesic omega-conotoxins from the vermivorous cone snail Conus
RT moncuri provide new insights into the evolution of conopeptides.";
RL Sci. Rep. 8:13397-13397(2018).
CC -!- FUNCTION: [Omega-conotoxin MoVIA]: Omega-conotoxins act at presynaptic
CC membranes, they bind and block voltage-gated calcium channels (Cav).
CC This toxin potently blocks mammalian N-type calcium channels
CC (Cav2.2/CACNA1B) (IC(50)=330 nM on human channels). It is 9-fold more
CC potent in displacing radiolabeled omega-conotoxin GVIA from fish brain
CC membranes than from human SH-SY5Y cells. {ECO:0000269|PubMed:30194442}.
CC -!- FUNCTION: [Omega-conotoxin MoVIB]: Omega-conotoxins act at presynaptic
CC membranes, they bind and block voltage-gated calcium channels (Cav).
CC This toxin potently blocks mammalian N-type calcium channels
CC (Cav2.2/CACNA1B) (IC(50)=600 nM on human channels). It is 60-fold more
CC potent in displacing radiolabeled omega-conotoxin GVIA from fish brain
CC membranes than from human SH-SY5Y cells. In vivo, when tested on rat
CC neuropathic pain model, this toxin shows an analgesic activity
CC (PubMed:30194442). {ECO:0000269|PubMed:30194442}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30194442}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:30194442}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:30194442}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC -!- MISCELLANEOUS: C.moncuri is a vermivorous cone snail. Both MoVIA and
CC MoVIB have an Arg-58 (Arg-13 in mature peptides) that replaces the
CC functionnally critical Tyr-13 found in potent Cav2.2/CACNA1B inhibitors
CC from fish-hunting species (such as MVIIA (AC P05484) and GVIA (AC
CC P01522)). {ECO:0000305|PubMed:30194442}.
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Biological Magnetic Resonance Data Bank;
CC URL="http://www.bmrb.wisc.edu/data_library/summary/index.php?bmrbId=30405";
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DR PDB; 6CEG; NMR; -; A=46-75.
DR PDBsum; 6CEG; -.
DR AlphaFoldDB; A0A384E129; -.
DR SMR; A0A384E129; -.
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; IPR004214; Conotoxin.
DR InterPro; IPR012321; Conotoxin_omega-typ_CS.
DR Pfam; PF02950; Conotoxin; 1.
DR PROSITE; PS60004; OMEGA_CONOTOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium channel impairing toxin; Direct protein sequencing;
KW Disulfide bond; Hydroxylation; Ion channel impairing toxin; Knottin;
KW Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated calcium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..45
FT /evidence="ECO:0000305"
FT /id="PRO_0000446312"
FT PEPTIDE 46..76
FT /note="Omega-conotoxin MoVIA"
FT /evidence="ECO:0000269|PubMed:30194442"
FT /id="PRO_0000446313"
FT PEPTIDE 46..75
FT /note="Omega-conotoxin MoVIB"
FT /evidence="ECO:0000269|PubMed:30194442"
FT /id="PRO_0000446314"
FT MOD_RES 49
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:30194442"
FT MOD_RES 55
FT /note="Hydroxyproline"
FT /evidence="ECO:0000269|PubMed:30194442"
FT DISULFID 46..61
FT /evidence="ECO:0000269|PubMed:30194442,
FT ECO:0000312|PDB:6CEG"
FT DISULFID 53..64
FT /evidence="ECO:0000269|PubMed:30194442,
FT ECO:0000312|PDB:6CEG"
FT DISULFID 60..71
FT /evidence="ECO:0000269|PubMed:30194442,
FT ECO:0000312|PDB:6CEG"
FT MUTAGEN 58
FT /note="R->Y: MoVIB-[R13Y]; 10.5-fold decrease in inhibition
FT potency of human Cav2.2/CACNA1B."
FT /evidence="ECO:0000269|PubMed:30194442"
FT TURN 55..57
FT /evidence="ECO:0007829|PDB:6CEG"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6CEG"
FT TURN 66..69
FT /evidence="ECO:0007829|PDB:6CEG"
SQ SEQUENCE 76 AA; 8587 MW; 6A25CE8C0076F9B2 CRC64;
MKLTCVVIVA VLFLTACQLI TADDSRSTQR HRALRSTTKL SMSTRCKPPG SKCSPSMRDC
CTTCISYTKR CRKYYN
