O16A_CONMR
ID O16A_CONMR Reviewed; 82 AA.
AC P56708; F6LPM9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 2.
DT 25-MAY-2022, entry version 78.
DE RecName: Full=Mu-conotoxin MrVIA {ECO:0000303|PubMed:7622492, ECO:0000303|PubMed:7727394};
DE AltName: Full=Conotoxin Mr6.5 {ECO:0000303|PubMed:22781954};
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].
RC TISSUE=Venom gland;
RX PubMed=22781954; DOI=10.1016/j.toxicon.2012.06.011;
RA Liu Z., Li H., Liu N., Wu C., Jiang J., Yue J., Jing Y., Dai Q.;
RT "Diversity and evolution of conotoxins in Conus virgo, Conus eburneus,
RT Conus imperialis and Conus marmoreus from the South China Sea.";
RL Toxicon 60:982-989(2012).
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 PROTEIN SEQUENCE OF 52-82, SYNTHESIS OF 52-82, MASS SPECTROMETRY, AND
RP 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 [4]
RP FUNCTION, AND SYNTHESIS OF 52-82.
RX PubMed=8890263; DOI=10.1152/jn.1996.76.3.1423;
RA Terlau H., Stocker M., Shon K.-J., McIntosh J.M., Olivera B.M.;
RT "MuO-conotoxin MrVIA inhibits mammalian sodium channels, but not through
RT site I.";
RL J. Neurophysiol. 76:1423-1429(1996).
RN [5]
RP FUNCTION.
RX PubMed=10627583; DOI=10.1523/jneurosci.20-01-00076.2000;
RA Safo P., Rosenbaum T., Shcherbatko A., Choi D.-Y., Han E.,
RA Toledo-Aral J.J., Olivera B.M., Brehm P., Mandel G.;
RT "Distinction among neuronal subtypes of voltage-activated sodium channels
RT by mu-conotoxin PIIIA.";
RL J. Neurosci. 20:76-80(2000).
RN [6]
RP FUNCTION, AND SYNTHESIS OF 52-82.
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 inhibits
CC rNav1.2/SCN2A (IC(50)=532 nM), rNav1.4/SCN4A (IC(50)=438 nM) and
CC rNav1.7/SCN9A (IC(50)=345 nM) (PubMed:10627583). It blocks Nav channels
CC by interacting mainly with the C-terminal part of the pore loop of
CC domain-3 (PubMed:16458302). It does not bind on site 1
CC (PubMed:8890263). At small concentration, this toxin also acts as a
CC calcium current agonist, whereas at higher doses it blocks fast-
CC inactivating calcium current (PubMed:7727394).
CC {ECO:0000269|PubMed:10627583, ECO:0000269|PubMed:16458302,
CC ECO:0000269|PubMed:7727394, ECO:0000269|PubMed:8890263}.
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:0000250|UniProtKB:Q26443}.
CC -!- DOMAIN: The cysteine framework is VI/VII (C-C-CC-C-C). {ECO:0000305}.
CC -!- MASS SPECTROMETRY: Mass=3487.8; Method=LSI;
CC Evidence={ECO:0000269|PubMed:7622492};
CC -!- MASS SPECTROMETRY: Mass=3488.1; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:7727394};
CC -!- SIMILARITY: Belongs to the conotoxin O1 superfamily. {ECO:0000305}.
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DR EMBL; JF322917; ADZ74146.1; -; mRNA.
DR PIR; A58586; A58586.
DR AlphaFoldDB; P56708; -.
DR SMR; P56708; -.
DR ConoServer; 1554; MrVIA.
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: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 Calcium channel impairing toxin; Direct protein sequencing; Disulfide bond;
KW Ion channel impairing toxin; 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_0000425737"
FT PEPTIDE 52..82
FT /note="Mu-conotoxin MrVIA"
FT /evidence="ECO:0000269|PubMed:7622492,
FT ECO:0000269|PubMed:7727394"
FT /id="PRO_0000044875"
FT DISULFID 53..71
FT /evidence="ECO:0000250|UniProtKB:Q26443"
FT DISULFID 60..76
FT /evidence="ECO:0000250|UniProtKB:Q26443"
FT DISULFID 70..81
FT /evidence="ECO:0000250|UniProtKB:Q26443"
SQ SEQUENCE 82 AA; 9267 MW; A11A2374FB58FC75 CRC64;
MKLTCMMIVA VLFLTAWTLV MADDSNNGLA NHFSKSRDEM EDPEASKLEK RACRKKWEYC
IVPIIGFIYC CPGLICGPFV CV
