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Protein

Alpha-conotoxin Vc1A

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

Functioni

Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. This synthetic peptide (produced without hydroxyproline, nor 4-carboxyglutamate) is a neuronal nAChR antagonist that acts as a powerful analgesic. It blocks nAChRs composed of alpha-3 or -5/beta-2 (IC50=7.2 µM), alpha-3/beta-2 (IC50=7.3 µM), alpha-3/beta-4 (IC50=4.2 µM), alpha-3 or -5/beta-4 (IC50<30 µM), alpha-4/beta-2 (IC50<30 µM), alpha-4/beta-4 (IC50<30 µM) and alpha/beta/gamma/delta (IC50<30 µM) subunits.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-conotoxin Vc1A
Short name:
ACV1
Short name:
Alpha-Vc1A
Alternative name(s):
Vc1.1
OrganismiConus victoriae (Queen Victoria cone)
Taxonomic identifieri319920 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri499. VcIA precursor.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Failed in phase II clinical trial. Was tested by Metabolic under the name ACV1 to treat neuropathic pain.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Propeptidei26 – 4722PRO_0000034896Add
BLAST
Peptidei50 – 6516Alpha-conotoxin Vc1APRO_0000034897Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi51 ↔ 57
Disulfide bondi52 ↔ 65
Modified residuei55 – 5514-hydroxyproline1 Publication
Modified residuei63 – 6314-carboxyglutamate1 Publication
Modified residuei65 – 651Cysteine amide1 Publication

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond, Gamma-carboxyglutamic acid, Hydroxylation

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
66
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi51 – 533Combined sources
Helixi55 – 606Combined sources
Helixi62 – 654Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H8SNMR-A50-65[»]
2MFXNMR-A50-65[»]
2MFYNMR-A50-65[»]
2MG6NMR-A50-65[»]
4TTLX-ray1.70A50-66[»]
ProteinModelPortaliP69747.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP69747.

Family & Domainsi

Domaini

The cysteine framework is I (CC-C-C). Alpha4/7 pattern.

Sequence similaritiesi

Belongs to the conotoxin A superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiIPR009958. Conotoxin_a-typ.
IPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PfamiPF07365. Toxin_8. 1 hit.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P69747-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGMRMMFTVF LLVVLATTVV SSTSGRREFR GRNAAAKASD LVSLTDKKRG
60
CCSDPRCNYD HPEICG
Length:66
Mass (Da):7,258
Last modified:April 26, 2005 - v1
Checksum:iC55B0951D5E7A28D
GO

Mass spectrometryi

Molecular mass is 1866.5 Da from positions 50 - 65. Determined by ESI. 1 Publication
Molecular mass is 1866 Da from positions 50 - 65. Determined by ESI. 1 Publication
Molecular mass is 1809.7 Da from positions 50 - 65. Determined by ESI. Without hydroxyPro-55, nor gamma-carboxyglutamic acid.1 Publication
Molecular mass is 1821.6 Da from positions 50 - 65. Determined by ESI. With hydroxyPro-55, but without gamma-carboxyglutamic acid.1 Publication

Cross-referencesi

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H8SNMR-A50-65[»]
2MFXNMR-A50-65[»]
2MFYNMR-A50-65[»]
2MG6NMR-A50-65[»]
4TTLX-ray1.70A50-66[»]
ProteinModelPortaliP69747.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri499. VcIA precursor.

Miscellaneous databases

EvolutionaryTraceiP69747.

Family and domain databases

InterProiIPR009958. Conotoxin_a-typ.
IPR018072. Conotoxin_a-typ_CS.
[Graphical view]
PfamiPF07365. Toxin_8. 1 hit.
[Graphical view]
PROSITEiPS60014. ALPHA_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo."
    Sandall D.W., Satkunanathan N., Keays D.A., Polidano M.A., Liping X., Pham V., Down J.G., Khalil Z., Livett B.G., Gayler K.R.
    Biochemistry 42:6904-6911(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 50-65, FUNCTION.
    Tissue: Venom duct.
  2. "Determining sequences and post-translational modifications of novel conotoxins in Conus victoriae using cDNA sequencing and mass spectrometry."
    Jakubowski J.A., Keays D.A., Kelley W.P., Sandall D.W., Bingham J.-P., Livett B.G., Gayler K.R., Sweedler J.V.
    J. Mass Spectrom. 39:548-557(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], MASS SPECTROMETRY, AMIDATION AT CYS-65, HYDROXYLATION AT PRO-55, GAMMA-CARBOXYGLUTAMATION AT GLU-63.
    Tissue: Venom and Venom duct.
  3. "A conus peptide blocks nicotinic receptors of unmyelinated axons in human nerves."
    Lang P.M., Burgstahler R., Haberberger R.V., Sippel W., Grafe P.
    NeuroReport 16:479-483(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  4. "Alpha-conotoxin Vc1.1 alleviates neuropathic pain and accelerates functional recovery of injured neurones."
    Satkunanathan N., Livett B., Gayler K., Sandall D., Down J., Khalil Z.
    Brain Res. 1059:149-158(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHARMACEUTICAL.
  5. "The synthesis, structural chracterisation and receptor specificity of the alpha-conotoxin Vc1.1."
    Clark R.J., Fischer H., Nevin S.T., Adams D.J., Craik D.J.
    J. Biol. Chem. 281:23254-23263(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF NON-POST-TRANSLATIONALY MODIFIED PEPTIDE, DISULFIDE, BONDS, MASS SPECTROMETRY, STRUCTURE BY NMR.

Entry informationi

Entry nameiCA1A_CONVC
AccessioniPrimary (citable) accession number: P69747
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 26, 2005
Last modified: July 22, 2015
This is version 51 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, 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.