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Protein

Omega-conotoxin MVIIA

Gene
N/A
Organism
Conus magus (Magus cone) (Magician's cone snail)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks N-type calcium channels (Cav2.2/CACNA1B).

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei58 – 581Important for calcium channel binding

GO - Molecular functioni

  1. ion channel inhibitor activity Source: InterPro

GO - Biological processi

  1. pathogenesis Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel impairing toxin, Ion channel impairing toxin, Neurotoxin, Presynaptic neurotoxin, Toxin, Voltage-gated calcium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Omega-conotoxin MVIIA
Alternative name(s):
SNX-111
INN: Ziconotide
OrganismiConus magus (Magus cone) (Magician's cone snail)
Taxonomic identifieri6492 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri1564. MVIIA precursor.

Subcellular locationi

GO - Cellular componenti

  1. other organism presynaptic membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Is available under the names Prialt by Neurex. It blocks acute pain in patients who no longer obtain relief from opiate drugs. It is 100 to 1000 times more potent than morphine. By blocking calcium channels it disable nerves that transmit pain signals.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi47 – 471K → A: Little decrease in activity. 1 Publication
Mutagenesisi58 – 581Y → A: Strong decrease in activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Propeptidei23 – 45232 PublicationsPRO_0000034914Add
BLAST
Peptidei46 – 7025Omega-conotoxin MVIIAPRO_0000034915Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi46 ↔ 61
Disulfide bondi53 ↔ 65
Disulfide bondi60 ↔ 70
Modified residuei70 – 701Cysteine amide

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
71
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi55 – 573Combined sources
Beta strandi60 – 634Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DW4NMR-A46-70[»]
1DW5NMR-A46-70[»]
1FEONMR-A46-70[»]
1MVINMR-A46-70[»]
1OMGNMR-A46-70[»]
1TT3NMR-A46-70[»]
1TTKNMR-A46-70[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05484.

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.
IPR012321. Conotoxin_omega-typ_CS.
[Graphical view]
PfamiPF02950. Conotoxin. 1 hit.
[Graphical view]
PROSITEiPS60004. OMEGA_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P05484-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKLTCVVIVA VLLLTACQLI TADDSRGTQK HRALRSTTKL STSTRCKGKG
60 70
AKCSRLMYDC CTGSCRSGKC G
Length:71
Mass (Da):7,587
Last modified:June 20, 2002 - v2
Checksum:iE2A32725C81AF31D
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421T → M in ADB93081 (PubMed:20363338).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ959111 Genomic DNA. Translation: ADB93081.1.
PIRiJH0700.

Cross-referencesi

Web resourcesi

Ziconotide Source

Web site on ziconotide

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ959111 Genomic DNA. Translation: ADB93081.1.
PIRiJH0700.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1DW4NMR-A46-70[»]
1DW5NMR-A46-70[»]
1FEONMR-A46-70[»]
1MVINMR-A46-70[»]
1OMGNMR-A46-70[»]
1TT3NMR-A46-70[»]
1TTKNMR-A46-70[»]
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri1564. MVIIA precursor.

Miscellaneous databases

EvolutionaryTraceiP05484.

Family and domain databases

InterProiIPR004214. Conotoxin.
IPR012321. Conotoxin_omega-typ_CS.
[Graphical view]
PfamiPF02950. Conotoxin. 1 hit.
[Graphical view]
PROSITEiPS60004. OMEGA_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Venom duct.
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. Cited for: PROTEIN SEQUENCE OF 46-70.
  4. "Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom."
    Olivera B.M., Cruz L.J., de Santos V., Lecheminant G.W., Griffin D., Zeikus R.D., McIntosh J.M., Galyean R., Varga J., Gray W.R., Rivier J.E.
    Biochemistry 26:2086-2090(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 46-70.
  5. "Determination of disulfide bridge pattern in omega-conopeptides."
    Chung D., Gaur S., Bell J.R., Ramachandran J., Nadasdi L.
    Int. J. Pept. Protein Res. 46:320-325(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  6. "Tyr13 is essential for the activity of omega-conotoxin MVIIA and GVIA, specific N-type calcium channel blockers."
    Kim J.-I., Takahashi M., Ohtake A., Wakamiya A., Sato K.
    Biochem. Biophys. Res. Commun. 206:449-454(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 46-70, MUTAGENESIS OF LYS-47 AND TYR-58.
  7. "Ziconotide: neuronal calcium channel blocker for treating severe chronic pain."
    Miljanich G.P.
    Curr. Med. Chem. 11:3029-3040(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHARMACEUTICAL USE FOR SEVERE CHRONIC PAIN TREATMENT.
  8. "Three-dimensional structure in solution of the calcium channel blocker omega-conotoxin MVIIA."
    Kohno T., Kim J.-I., Kobayashi K., Kodera Y., Maeda T., Sato K.
    Biochemistry 34:10256-10265(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 46-70, DISULFIDE BONDS.
  9. "Solution structure of omega-conotoxin MVIIA using 2D NMR spectroscopy."
    Basus V.J., Nadasdi L., Ramachandran J., Miljanich G.P.
    FEBS Lett. 370:163-169(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 46-70, DISULFIDE BONDS.
  10. "A consensus structure for omega-conotoxins with different selectivities for voltage-sensitive calcium channel subtypes: comparison of MVIIA, SVIB and SNX-202."
    Nielsen K.J., Thomas L., Lewis R.J., Alewood P.F., Craik D.J.
    J. Mol. Biol. 263:297-310(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 46-70, DISULFIDE BONDS.
  11. "Structure-activity relationships of omega-conotoxins MVIIA, MVIIC and 14 loop splice hybrids at N and P/Q-type calcium channels."
    Nielsen K.J., Adams D., Thomas L., Bond T., Alewood P.F., Craik D.J., Lewis R.J.
    J. Mol. Biol. 289:1405-1421(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 46-70, DISULFIDE BONDS.
  12. "Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange."
    Atkinson R.A., Kieffer B., Dejaegere A., Sirockin F., Lefevre J.-F.
    Biochemistry 39:3908-3919(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 46-70, DISULFIDE BONDS.
  13. "Solution structure and backbone dynamics of an omega-conotoxin precursor."
    Goldenberg D.P., Koehn R.E., Gilbert D.E., Wagner G.
    Protein Sci. 10:538-550(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 46-70, DISULFIDE BONDS.

Entry informationi

Entry nameiCO17A_CONMA
AccessioniPrimary (citable) accession number: P05484
Secondary accession number(s): D6C4G9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: June 20, 2002
Last modified: March 4, 2015
This is version 105 of the entry and version 2 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

External Data

Dasty 3

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 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.