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Protein

Mu-conotoxin GIIIA

Gene
N/A
Organism
Conus geographus (Geography cone) (Nubecula geographus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Mu-conotoxins block voltage-gated sodium channels (Nav). This toxin potently blocks Nav1.4/SCN4A. It also moderately blocks rNav1.1/SCN1A, rNav1.2/SCN2A, and mNav1.6/SCN8A. The inhibition is reversible. Induces paralysis in vertebrates.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei63 – 631Important for binding sodium channel

GO - Molecular functioni

  1. sodium channel inhibitor activity Source: InterPro

GO - Biological processi

  1. pathogenesis Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Ion channel impairing toxin, Neurotoxin, Toxin, Voltage-gated sodium channel impairing toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Mu-conotoxin GIIIA
Alternative name(s):
G3.9
Geographutoxin I
Short name:
GTx-I
Myotoxin I
OrganismiConus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifieri6491 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri1570. GIIIA [R13A].
1464. GIIIA precursor.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi63 – 631R → A: Loss of activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Propeptidei20 – 50312 PublicationsPRO_0000246004Add
BLAST
Peptidei51 – 7222Mu-conotoxin GIIIAPRO_0000044493Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi53 ↔ 651 Publication
Disulfide bondi54 ↔ 701 Publication
Modified residuei56 – 5614-hydroxyproline; partial3 Publications
Modified residuei57 – 5714-hydroxyproline; partial3 Publications
Disulfide bondi60 ↔ 711 Publication
Modified residuei67 – 6714-hydroxyproline3 Publications
Modified residuei72 – 721Alanine amide3 Publications

Post-translational modificationi

Hydroxylated; hydroxylations improve the ability to block.2 Publications

Keywords - PTMi

Amidation, Cleavage on pair of basic residues, Disulfide bond, Hydroxylation

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
74
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi53 – 575Combined sources
Helixi63 – 653Combined sources
Turni69 – 713Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TCGNMR-A51-72[»]
1TCHNMR-A51-72[»]
1TCJNMR-A51-72[»]
1TCKNMR-A51-72[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01523.

Family & Domainsi

Domaini

The cysteine framework is III (CC-C-C-CC). Classified in the M-4 branch, since 4 residues stand between the fourth and the fifth cysteine residues.

Sequence similaritiesi

Belongs to the conotoxin M superfamily.Curated

Keywords - Domaini

Signal

Family and domain databases

InterProiIPR008036. Conotoxin_mu-typ.
[Graphical view]
PfamiPF05374. Mu-conotoxin. 1 hit.
[Graphical view]
PROSITEiPS60013. MU_CONOTOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P01523-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSKLGVLLTI CLLLFPLTAL PMDGDEPANR PVERMQDNIS SEQYPLFEKR
60 70
RDCCTPPKKC KDRQCKPQRC CAGR
Length:74
Mass (Da):8,455
Last modified:July 11, 2006 - v2
Checksum:i94CC38599C8374BA
GO

Sequence databases

PIRiA01786. MXKN1.

Cross-referencesi

Sequence databases

PIRiA01786. MXKN1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TCGNMR-A51-72[»]
1TCHNMR-A51-72[»]
1TCJNMR-A51-72[»]
1TCKNMR-A51-72[»]
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

ConoServeri1570. GIIIA [R13A].
1464. GIIIA precursor.

Miscellaneous databases

EvolutionaryTraceiP01523.

Family and domain databases

InterProiIPR008036. Conotoxin_mu-typ.
[Graphical view]
PfamiPF05374. Mu-conotoxin. 1 hit.
[Graphical view]
PROSITEiPS60013. MU_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Definition of the M-conotoxin superfamily: characterization of novel peptides from molluscivorous Conus venoms."
    Corpuz G.P., Jacobsen R.B., Jimenez E.C., Watkins M., Walker C., Colledge C., Garrett J.E., McDougal O., Li W., Gray W.R., Hillyard D.R., Rivier J., McIntosh J.M., Cruz L.J., Olivera B.M.
    Biochemistry 44:8176-8186(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Venom duct.
  2. "Conus geographus toxins that discriminate between neuronal and muscle sodium channels."
    Cruz L.J., Gray W.R., Olivera B.M., Zeikus R.D., Kerr L., Yoshikami D., Moczydlowski E.
    J. Biol. Chem. 260:9280-9288(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 51-72, FUNCTION, BIOASSAY.
    Tissue: Venom.
  3. "The amino acid sequences of homologous hydroxyproline-containing myotoxins from the marine snail Conus geographus venom."
    Sato S., Nakamura H., Ohizumi Y., Kobayashi J., Hirata Y.
    FEBS Lett. 155:277-280(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 51-72.
    Tissue: Venom.
  4. "Disulfide pairings in geographutoxin I, a peptide neurotoxin from Conus geographus."
    Hidaka Y., Sato K., Nakamura H., Kobayashi J., Ohizumi Y., Simonishi Y.
    FEBS Lett. 264:29-32(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS.
  5. "Role of hydroxyprolines in the in vitro oxidative folding and biological activity of conotoxins."
    Lopez-Vera E., Walewska A., Skalicky J.J., Olivera B.M., Bulaj G.
    Biochemistry 47:1741-1751(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 51-72, ROLE OF HYDROXYLATION.
  6. "Pruning nature: biodiversity-derived discovery of novel sodium channel blocking conotoxins from Conus bullatus."
    Holford M., Zhang M.-M., Gowd K.H., Azam L., Green B.R., Watkins M., Ownby J.-P., Yoshikami D., Bulaj G., Olivera B.M.
    Toxicon 53:90-98(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "mu-Conotoxins that differentially block sodium channels Nav1.1 through 1.8 identify those responsible for action potentials in sciatic nerve."
    Wilson M.J., Yoshikami D., Azam L., Gajewiak J., Olivera B.M., Bulaj G., Zhang M.M.
    Proc. Natl. Acad. Sci. U.S.A. 108:10302-10307(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION ON SODIUM CHANNELS, SYNTHESIS OF 51-72.
  8. "Solution structure of mu-conotoxin GIIIA analysed by 2D-NMR and distance geometry calculations."
    Ott K.-H., Becker S., Gordon R.D., Rueterjans H.
    FEBS Lett. 278:160-166(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 51-72, HYDROXYLATION AT PRO-56; PRO-57 AND PRO-67, AMIDATION AT ALA-72, DISULFIDE BONDS.
  9. "Tertiary structure of conotoxin GIIIA in aqueous solution."
    Lancelin J.-M., Kohda D., Tate S., Yanagawa Y., Abe T., Satake M., Inagaki F.
    Biochemistry 30:6908-6916(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 51-72, HYDROXYLATION AT PRO-56; PRO-57 AND PRO-67, AMIDATION AT ALA-72, DISULFIDE BONDS.
  10. "Structure-activity relationships of mu-conotoxin GIIIA: structure determination of active and inactive sodium channel blocker peptides by NMR and simulated annealing calculations."
    Wakamatsu K., Kohda D., Hatanaka H., Lancelin J.M., Ishida Y., Oya M., Nakamura H., Inagaki F., Sato K.
    Biochemistry 31:12577-12584(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 51-72, SYNTHESIS OF 51-72, DISULFIDE BONDS, MUTAGENESIS OF ARG-63.

Entry informationi

Entry nameiCM3A_CONGE
AccessioniPrimary (citable) accession number: P01523
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 11, 2006
Last modified: January 7, 2015
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

Miscellaneous

Does not block rNav1.3/SCN3A, rNav1.5/SCN5A, rNav1.7/SCN9A, and rNav1.8/SCN10A (PubMed:21652775). Nav1.4/SCN4A sodium channels but did not affect folding.1 Publication

Keywords - Technical termi

3D-structure, Direct protein sequencing

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

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 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.