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P01523 (CM3A_CONGE) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Mu-conotoxin GIIIA
Alternative name(s):
G3.9
Geographutoxin I
Short name=GTx-I
Myotoxin I
OrganismConus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifier6491 [NCBI]
Taxonomic lineageEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Protein attributes

Sequence length74 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2 Ref.6 Ref.7

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom duct.

Domain

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.

Post-translational modification

Hydroxylated; hydroxylations improve the ability to block.

Miscellaneous

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

Sequence similarities

Belongs to the conotoxin M superfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 5031
PRO_0000246004
Peptide51 – 7222Mu-conotoxin GIIIA Ref.2 Ref.3
PRO_0000044493

Sites

Site631Important for binding sodium channel

Amino acid modifications

Modified residue5614-hydroxyproline; partial Ref.2 Ref.8 Ref.9
Modified residue5714-hydroxyproline; partial Ref.2 Ref.8 Ref.9
Modified residue6714-hydroxyproline Ref.2 Ref.8 Ref.9
Modified residue721Alanine amide Ref.2 Ref.8 Ref.9
Disulfide bond53 ↔ 65 Ref.4 Ref.8 Ref.9 Ref.10
Disulfide bond54 ↔ 70 Ref.4 Ref.8 Ref.9 Ref.10
Disulfide bond60 ↔ 71 Ref.4 Ref.8 Ref.9 Ref.10

Experimental info

Mutagenesis631R → A: Loss of activity. Ref.10

Secondary structure

....... 74
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01523 [UniParc].

Last modified July 11, 2006. Version 2.
Checksum: 94CC38599C8374BA

FASTA748,455
        10         20         30         40         50         60 
MSKLGVLLTI CLLLFPLTAL PMDGDEPANR PVERMQDNIS SEQYPLFEKR RDCCTPPKKC 

        70 
KDRQCKPQRC CAGR 

« Hide

References

[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.

Cross-references

Sequence databases

PIRMXKN1. A01786.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1TCGNMR-A51-72[»]
1TCHNMR-A51-72[»]
1TCJNMR-A51-72[»]
1TCKNMR-A51-72[»]
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

ConoServer1570. GIIIA [R13A].
1464. GIIIA precursor.

Family and domain databases

InterProIPR008036. Conotoxin_mu-typ.
[Graphical view]
PfamPF05374. Mu-conotoxin. 1 hit.
[Graphical view]
PROSITEPS60013. MU_CONOTOXIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01523.

Entry information

Entry nameCM3A_CONGE
AccessionPrimary (citable) accession number: P01523
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 11, 2006
Last modified: February 19, 2014
This is version 98 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