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Protein

Mu-conotoxin MrVIB

Gene
N/A
Organism
Conus marmoreus (Marble cone)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Mu-conotoxins block voltage-gated sodium channels. Has a preference for Nav1.4/SCN4A over Nav1.2/SCN2A sodium channels. Blocks Nav channels by interacting mainly with the C-terminal part of the pore loop of domain-3. Also blocks fast-inactivating calcium current. Blocks Nav1.8/SCN10A sodium channels and has potent and long-lasting local anesthetic effects. Can also block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Mu-conotoxin MrVIB
Alternative name(s):
CGX-1002
OrganismiConus marmoreus (Marble cone)
Taxonomic identifieri42752 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri597. MrVIB precursor.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Is under preclinical trial by Cognetix Inc under the name CGX-1002 as a local anesthetic agent.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence analysisAdd
BLAST
Propeptidei23 – 4927PRO_0000034902Add
BLAST
Peptidei52 – 8231Mu-conotoxin MrVIBPRO_0000034903Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi53 ↔ 711 Publication
Disulfide bondi60 ↔ 761 Publication
Disulfide bondi70 ↔ 811 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi69 – 713Combined sources
Beta strandi78 – 825Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RMKNMR-A52-82[»]
ProteinModelPortaliQ26443.
SMRiQ26443. Positions 52-82.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ26443.

Family & Domainsi

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.
The cysteine framework is VI/VII (C-C-CC-C-C).

Sequence similaritiesi

Belongs to the conotoxin O1 superfamily.Curated

Keywords - Domaini

Knottin, Signal

Family and domain databases

InterProiIPR004214. Conotoxin.
[Graphical view]
PfamiPF02950. Conotoxin. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q26443-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLTCMMIVA VLFLTAWTLV MADDSNNGLA NHFLKSRDEM EDPEASKLEK
60 70 80
RACSKKWEYC IVPILGFVYC CPGLICGPFV CV
Length:82
Mass (Da):9,210
Last modified:November 1, 1996 - v1
Checksum:iB617F8652A48F5D6
GO

Mass spectrometryi

Molecular mass is 3404.8 Da from positions 52 - 82. Determined by LSI. 1 Publication
Molecular mass is 3404.9 Da from positions 52 - 82. Determined by ESI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S78990 mRNA. Translation: AAB34916.1.
PIRiB58586.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S78990 mRNA. Translation: AAB34916.1.
PIRiB58586.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1RMKNMR-A52-82[»]
ProteinModelPortaliQ26443.
SMRiQ26443. Positions 52-82.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri597. MrVIB precursor.

Miscellaneous databases

EvolutionaryTraceiQ26443.

Family and domain databases

InterProiIPR004214. Conotoxin.
[Graphical view]
PfamiPF02950. Conotoxin. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "A new family of conotoxins that blocks voltage-gated sodium channels."
    McIntosh J.M., Hasson A., Spira M.E., Gray W.R., Li W., Marsh M., Hillyard D.R., Olivera B.M.
    J. Biol. Chem. 270:16796-16802(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 52-82, MASS SPECTROMETRY.
    Tissue: Venom.
  2. "New sodium channel-blocking conotoxins also affect calcium currents in Lymnaea neurons."
    Fainzilber M., van der Schors R., Lodder J.C., Li K.W., Geraerts W.P., Kits K.S.
    Biochemistry 34:5364-5371(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 52-82, CHARACTERIZATION, MASS SPECTROMETRY.
    Tissue: Venom.
  3. "Structures of muO-conotoxins from Conus marmoreus. Inhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons."
    Daly N.L., Ekberg J.A., Thomas L., Adams D.J., Lewis R.J., Craik D.J.
    J. Biol. Chem. 279:25774-25782(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 52-82, DISULFIDE BONDS.
  4. "Synthetic muO-conotoxin MrVIB blocks TTX-resistant sodium channel NaV1.8 and has a long-lasting analgesic activity."
    Bulaj G., Zhang M.M., Green B.R., Fiedler B., Layer R.T., Wei S., Nielsen J.S., Low S.J., Klein B.D., Wagstaff J.D., Chicoine L., Harty T.P., Terlau H., Yoshikami D., Olivera B.M.
    Biochemistry 45:7404-7414(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 52-82, FUNCTION.
  5. "The muO-conotoxin MrVIA inhibits voltage-gated sodium channels by associating with domain-3."
    Zorn S., Leipold E., Hansel A., Bulaj G., Olivera B.M., Terlau H., Heinemann S.H.
    FEBS Lett. 580:1360-1364(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 52-82, FUNCTION.

Entry informationi

Entry nameiCO16B_CONMR
AccessioniPrimary (citable) accession number: Q26443
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: December 9, 2015
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.