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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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
PropeptideiPRO_000003489626 – 47Add BLAST22
PeptideiPRO_000003489750 – 65Alpha-conotoxin Vc1AAdd BLAST16

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi51 ↔ 57
Disulfide bondi52 ↔ 65
Modified residuei554-hydroxyproline1 Publication1
Modified residuei634-carboxyglutamate1 Publication1
Modified residuei65Cysteine amide1 Publication1

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

166
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi51 – 53Combined sources3
Helixi55 – 60Combined sources6
Helixi62 – 65Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H8SNMR-A50-65[»]
2MFXNMR-A50-65[»]
2MFYNMR-A50-65[»]
2MG6NMR-A50-65[»]
2N07NMR-X50-66[»]
4TTLX-ray1.70A50-66[»]
ProteinModelPortaliP69747.
SMRiP69747.
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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H8SNMR-A50-65[»]
2MFXNMR-A50-65[»]
2MFYNMR-A50-65[»]
2MG6NMR-A50-65[»]
2N07NMR-X50-66[»]
4TTLX-ray1.70A50-66[»]
ProteinModelPortaliP69747.
SMRiP69747.
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...

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: November 2, 2016
This is version 53 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.