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P05484 (CO17A_CONMA) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Omega-conotoxin MVIIA
Alternative name(s):
SNX-111
INN=Ziconotide
OrganismConus magus (Magus cone) (Magician's cone snail)
Taxonomic identifier6492 [NCBI]
Taxonomic lineageEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Protein attributes

Sequence length71 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom duct.

Domain

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).

Pharmaceutical use

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.

Sequence similarities

Belongs to the conotoxin O1 superfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 4523
PRO_0000034914
Peptide46 – 7025Omega-conotoxin MVIIA Ref.3 Ref.4
PRO_0000034915

Sites

Site581Important for calcium channel binding

Amino acid modifications

Modified residue701Cysteine amide
Disulfide bond46 ↔ 61 Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Disulfide bond53 ↔ 65 Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13
Disulfide bond60 ↔ 70 Ref.5 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13

Experimental info

Mutagenesis471K → A: Little decrease in activity. Ref.6
Mutagenesis581Y → A: Strong decrease in activity. Ref.6
Sequence conflict421T → M in ADB93081. Ref.2

Secondary structure

..... 71
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05484 [UniParc].

Last modified June 20, 2002. Version 2.
Checksum: E2A32725C81AF31D

FASTA717,587
        10         20         30         40         50         60 
MKLTCVVIVA VLLLTACQLI TADDSRGTQK HRALRSTTKL STSTRCKGKG AKCSRLMYDC 

        70 
CTGSCRSGKC G 

« Hide

References

[1]"Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes."
Lewis R.J., Nielsen K.J., Craik D.J., Loughnan M.L., Adams D.A., Sharpe I.A., Luchian T., Adams D.J., Bond T., Thomas L., Jones A., Matheson J.-L., Drinkwater R., Andrews P.R., Alewood P.F.
J. Biol. Chem. 275:35335-35344(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Venom duct.
[2]"Evolution of Conus peptide toxins: analysis of Conus californicus Reeve, 1844."
Biggs J.S., Watkins M., Puillandre N., Ownby J.P., Lopez-Vera E., Christensen S., Moreno K.J., Bernaldez J., Licea-Navarro A., Corneli P.S., Olivera B.M.
Mol. Phylogenet. Evol. 56:1-12(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Peptide neurotoxins from fish-hunting cone snails."
Olivera B.M., Gray W.R., Zeikus R.D., McIntosh J.M., Varga J., Rivier J.E., de Santos V., Cruz L.J.
Science 230:1338-1343(1985) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Ziconotide Source

Web site on ziconotide

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
FJ959111 Genomic DNA. Translation: ADB93081.1.
PIRJH0700.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DW4NMR-A46-70[»]
1DW5NMR-A46-70[»]
1FEONMR-A46-70[»]
1MVINMR-A46-70[»]
1OMGNMR-A46-70[»]
1TT3NMR-A46-70[»]
1TTKNMR-A46-70[»]
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

ConoServer1564. MVIIA precursor.

Family and domain databases

InterProIPR004214. Conotoxin.
IPR012321. Conotoxin_omega-typ_CS.
[Graphical view]
PfamPF02950. Conotoxin. 1 hit.
[Graphical view]
PROSITEPS60004. OMEGA_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP05484.

Entry information

Entry nameCO17A_CONMA
AccessionPrimary (citable) accession number: P05484
Secondary accession number(s): D6C4G9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: June 20, 2002
Last modified: July 9, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references