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Protein

Omega-conotoxin MVIIA

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

Functioni

Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC50=180 nM). When injected in mamals, show adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei58Important for calcium channel binding1 Publication1

GO - Molecular functioni

Keywordsi

Molecular functionCalcium 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 lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaNeogastropodaConoideaConidaeConusPionoconus

Organism-specific databases

ConoServeri1564 MVIIA precursor

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Toxic dosei

LD50 is 0.10 mg/kg by intramuscular injection into goldfish (C.carassius).1 Publication

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.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47K → A: Little decrease in activity. 1 Publication1
Mutagenesisi48 – 52GKGAK → AAGKP: 4-fold decrease in inhibition of Cav2.2; decrease in efficacy to kill goldfish (LD(50) is 5.20 mg/kg by intramuscular injection) (mutant omega-1). 1 Publication5
Mutagenesisi56 – 59LMYD → IAYN: 3-fold increase in inhibition of Cav2.2; decrease in efficacy to kill goldfish (LD(50) is 11.6 mg/kg by intramuscular injection) (mutant omega-2). 1 Publication4
Mutagenesisi56L → I: 1.8-fold decrease in inhibition of Cav2.2; decrease in efficacy to kill goldfish (LD(50) is 0.93 mg/kg by intramuscular injection) (mutant omega-5). 1 Publication1
Mutagenesisi57M → A: 2.11-fold decrease in inhibition of Cav2.2; decrease in efficacy to kill goldfish (LD(50) is 1.80 mg/kg by intramuscular injection) (mutant omega-4). 1 Publication1
Mutagenesisi58Y → A: Strong decrease in activity. 1 Publication1
Mutagenesisi59D → N: 2.8-fold increase in inhibition of Cav2.2; decrease in efficacy to kill goldfish (LD(50) is 0.20 mg/kg by intramuscular injection) (mutant omega-3). 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000003491423 – 452 PublicationsAdd BLAST23
PeptideiPRO_000003491546 – 70Omega-conotoxin MVIIA2 PublicationsAdd BLAST25

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi46 ↔ 617 Publications
Disulfide bondi53 ↔ 657 Publications
Disulfide bondi60 ↔ 707 Publications
Modified residuei70Cysteine amide1 Publication1

Keywords - PTMi

Amidation, Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom duct.2 Publications

Structurei

Secondary structure

171
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SMRiP05484
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05484

Family & Domainsi

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.7 Publications
The cysteine framework is VI/VII (C-C-CC-C-C).Curated

Sequence similaritiesi

Belongs to the conotoxin O1 superfamily.Curated

Keywords - Domaini

Knottin, Signal

Family and domain databases

InterProiView protein in InterPro
IPR004214 Conotoxin
IPR012321 Conotoxin_omega-typ_CS
PfamiView protein in Pfam
PF02950 Conotoxin, 1 hit
PROSITEiView protein in PROSITE
PS60004 OMEGA_CONOTOXIN, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti42T → M in ADB93081 (PubMed:20363338).Curated1

Sequence databases

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

Similar proteinsi

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DW4NMR-A46-70[»]
1DW5NMR-A46-70[»]
1FEONMR-A46-70[»]
1MVINMR-A46-70[»]
1OMGNMR-A46-70[»]
1TT3NMR-A46-70[»]
1TTKNMR-A46-70[»]
SMRiP05484
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri1564 MVIIA precursor

Miscellaneous databases

EvolutionaryTraceiP05484

Family and domain databases

InterProiView protein in InterPro
IPR004214 Conotoxin
IPR012321 Conotoxin_omega-typ_CS
PfamiView protein in Pfam
PF02950 Conotoxin, 1 hit
PROSITEiView protein in PROSITE
PS60004 OMEGA_CONOTOXIN, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiO17A_CONMA
AccessioniPrimary (citable) accession number: P05484
Secondary accession number(s): D6C4G9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: June 20, 2002
Last modified: October 10, 2018
This is version 114 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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