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P05484

- CO17A_CONMA

UniProt

P05484 - CO17A_CONMA

Protein

Omega-conotoxin MVIIA

Gene
N/A
Organism
Conus magus (Magus cone) (Magician's cone snail)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    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

    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 – 573
    Beta strandi60 – 634

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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

    MKLTCVVIVA VLLLTACQLI TADDSRGTQK HRALRSTTKL STSTRCKGKG   50
    AKCSRLMYDC CTGSCRSGKC G 71
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    FJ959111 Genomic DNA. Translation: ADB93081.1 .
    PIRi JH0700.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1DW4 NMR - A 46-70 [» ]
    1DW5 NMR - A 46-70 [» ]
    1FEO NMR - A 46-70 [» ]
    1MVI NMR - A 46-70 [» ]
    1OMG NMR - A 46-70 [» ]
    1TT3 NMR - A 46-70 [» ]
    1TTK NMR - A 46-70 [» ]
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    ConoServeri 1564. MVIIA precursor.

    Miscellaneous databases

    EvolutionaryTracei P05484.

    Family and domain databases

    InterProi IPR004214. Conotoxin.
    IPR012321. Conotoxin_omega-typ_CS.
    [Graphical view ]
    Pfami PF02950. Conotoxin. 1 hit.
    [Graphical view ]
    PROSITEi PS60004. OMEGA_CONOTOXIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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(1987) [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(1995) [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(1995) [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(2004) [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(1995) [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(1995) [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(1996) [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(1999) [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(2000) [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(2001) [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: October 1, 2014
    This is version 102 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