O16B_CONMR
ID O16B_CONMR Reviewed; 82 AA.
AC Q26443;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Mu-conotoxin MrVIB {ECO:0000303|PubMed:7622492, ECO:0000303|PubMed:7727394};
DE AltName: Full=CGX-1002;
DE Flags: Precursor;
OS Conus marmoreus (Marble cone).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Caenogastropoda; Neogastropoda; Conoidea; Conidae; Conus; Conus.
OX NCBI_TaxID=42752;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 52-82, MASS SPECTROMETRY,
RP AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=7622492; DOI=10.1074/jbc.270.28.16796;
RA McIntosh J.M., Hasson A., Spira M.E., Gray W.R., Li W., Marsh M.,
RA Hillyard D.R., Olivera B.M.;
RT "A new family of conotoxins that blocks voltage-gated sodium channels.";
RL J. Biol. Chem. 270:16796-16802(1995).
RN [2]
RP PROTEIN SEQUENCE OF 52-82, FUNCTION, MASS SPECTROMETRY, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Venom;
RX PubMed=7727394; DOI=10.1021/bi00016a007;
RA Fainzilber M., van der Schors R., Lodder J.C., Li K.W., Geraerts W.P.,
RA Kits K.S.;
RT "New sodium channel-blocking conotoxins also affect calcium currents in
RT Lymnaea neurons.";
RL Biochemistry 34:5364-5371(1995).
RN [3]
RP STRUCTURE BY NMR OF 52-82, AND DISULFIDE BONDS.
RX PubMed=15044438; DOI=10.1074/jbc.m313002200;
RA Daly N.L., Ekberg J.A., Thomas L., Adams D.J., Lewis R.J., Craik D.J.;
RT "Structures of muO-conotoxins from Conus marmoreus. Inhibitors of
RT tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian
RT sensory neurons.";
RL J. Biol. Chem. 279:25774-25782(2004).
RN [4]
RP SYNTHESIS OF 52-82, AND FUNCTION.
RX PubMed=16752929; DOI=10.1021/bi060159+;
RA Bulaj G., Zhang M.M., Green B.R., Fiedler B., Layer R.T., Wei S.,
RA Nielsen J.S., Low S.J., Klein B.D., Wagstaff J.D., Chicoine L., Harty T.P.,
RA Terlau H., Yoshikami D., Olivera B.M.;
RT "Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8
RT and has a long-lasting analgesic activity.";
RL Biochemistry 45:7404-7414(2006).
RN [5]
RP SYNTHESIS OF 52-82, AND FUNCTION.
RX PubMed=16458302; DOI=10.1016/j.febslet.2006.01.057;
RA Zorn S., Leipold E., Hansel A., Bulaj G., Olivera B.M., Terlau H.,
RA Heinemann S.H.;
RT "The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by
RT associating with domain-3.";
RL FEBS Lett. 580:1360-1364(2006).
CC -!- FUNCTION: MuO-conotoxins are gating-modifier toxins that inhibit sodium
CC current by trapping the domain II voltage sensor in the closed position
CC to prevent opening of the sodium channel. This toxin has a preference
CC for Nav1.4/SCN4A over Nav1.2/SCN2A sodium channels. It blocks Nav
CC channels by interacting mainly with the C-terminal part of the pore
CC loop of domain-3. It also blocks fast-inactivating calcium current.
CC Blocks Nav1.8/SCN10A sodium channels and has potent and long-lasting
CC local anesthetic effects. It can also block propagation of action
CC potentials in A- and C-fibers in sciatic nerve as well as skeletal
CC muscle in isolated preparations. {ECO:0000269|PubMed:16458302,
CC ECO:0000269|PubMed:16752929}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7622492,
CC ECO:0000269|PubMed:7727394}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom duct.
CC {ECO:0000305|PubMed:7622492, ECO:0000305|PubMed:7727394}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin.
CC {ECO:0000269|PubMed:15044438}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C).
CC -!- MASS SPECTROMETRY: Mass=3404.8; Method=LSI;
CC Evidence={ECO:0000269|PubMed:7622492};
CC -!- MASS SPECTROMETRY: Mass=3404.9; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:7727394};
CC -!- MISCELLANEOUS: This peptide was under preclinical trial by Cognetix Inc
CC under the name CGX-1002 as a local anesthetic agent.
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR EMBL; S78990; AAB34916.1; -; mRNA.
DR PIR; B58586; B58586.
DR PDB; 1RMK; NMR; -; A=52-82.
DR PDBsum; 1RMK; -.
DR AlphaFoldDB; Q26443; -.
DR SMR; Q26443; -.
DR ConoServer; 597; MrVIB precursor.
DR EvolutionaryTrace; Q26443; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008200; F:ion channel inhibitor activity; IEA:InterPro.
DR GO; GO:0017080; F:sodium channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR004214; Conotoxin.
DR Pfam; PF02950; Conotoxin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Knottin; Neurotoxin; Secreted; Signal; Toxin;
KW Voltage-gated sodium channel impairing toxin.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..49
FT /evidence="ECO:0000269|PubMed:7622492,
FT ECO:0000269|PubMed:7727394"
FT /id="PRO_0000034902"
FT PEPTIDE 52..82
FT /note="Mu-conotoxin MrVIB"
FT /evidence="ECO:0000269|PubMed:7622492,
FT ECO:0000269|PubMed:7727394"
FT /id="PRO_0000034903"
FT DISULFID 53..71
FT /evidence="ECO:0000269|PubMed:15044438,
FT ECO:0000312|PDB:1RMK"
FT DISULFID 60..76
FT /evidence="ECO:0000269|PubMed:15044438,
FT ECO:0000312|PDB:1RMK"
FT DISULFID 70..81
FT /evidence="ECO:0000269|PubMed:15044438,
FT ECO:0000312|PDB:1RMK"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1RMK"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:1RMK"
SQ SEQUENCE 82 AA; 9210 MW; B617F8652A48F5D6 CRC64;
MKLTCMMIVA VLFLTAWTLV MADDSNNGLA NHFLKSRDEM EDPEASKLEK RACSKKWEYC
IVPILGFVYC CPGLICGPFV CV
