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P07231 (CKG_CONGE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 98. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Conantokin-G

Short name=Con-G
Alternative name(s):
CGX-1007
Conotoxin GV
Sleeper peptide
OrganismConus geographus (Geography cone) (Nubecula geographus)
Taxonomic identifier6491 [NCBI]
Taxonomic lineageEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Protein attributes

Sequence length100 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin is selective for the NR2B/GRIN2B subunit. Induces sleep-like symptoms in young mice and hyperactivity in older mice. Ref.3

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom duct.

Pharmaceutical use

Failed in phase II clinical trial. Was tested under the name CGX-1007 by Cognetix Inc. to treat convulsion and epilepsy.

Miscellaneous

The mature peptide does not contain cysteine residue.

Sequence similarities

Belongs to the conotoxin B superfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121
Propeptide22 – 8059
PRO_0000035060
Peptide81 – 9717Conantokin-G
PRO_0000035061

Regions

Region61 – 8020Gamma-carboxylation recognition sequence that plays a role in the conversion of Glu to carboxy-Glu (Gla) Probable

Sites

Metal binding901Divalent metal cation; via 4-carboxyglutamate
Metal binding941Divalent metal cation; via 4-carboxyglutamate
Site851Important for selectivity

Amino acid modifications

Modified residue8314-carboxyglutamate Ref.2
Modified residue8414-carboxyglutamate Ref.2
Modified residue8714-carboxyglutamate Ref.2
Modified residue9014-carboxyglutamate Ref.2
Modified residue9414-carboxyglutamate Ref.2
Modified residue971Asparagine amide Ref.2

Natural variations

Natural variant851L → V. Ref.1

Experimental info

Mutagenesis851L → I: No loss of inhibition of NR1a/NR2B receptor; no inhibition of NR1a/NR2A receptor (as for the wild-type). Ref.4
Mutagenesis851L → V: No loss of inhibition of NR1a/NR2B receptor; no inhibition of NR1a/NR2A receptor (as for the wild-type). Ref.4
Mutagenesis851L → Y: Little loss of inhibition of NR1a/NR2B receptor; 70% of inhibition of NR1a/NR2A receptor. Ref.4

Secondary structure

... 100
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P07231 [UniParc].

Last modified December 15, 1998. Version 2.
Checksum: 3B0050FDFF2B9DFB

FASTA10011,267
        10         20         30         40         50         60 
MHLYTYLYLL VPLVTFHLIL GTGTLDDGGA LTERRSADAT ALKAEPVLLQ KSAARSTDDN 

        70         80         90        100 
GKDRLTQMKR ILKQRGNKAR GEEELQENQE LIREKSNGKR 

« Hide

References

[1]"Conantokin-G precursor and its role in gamma-carboxylation by a vitamin K-dependent carboxylase from a Conus snail."
Bandyopadhyay P.K., Colledge C.J., Walker C.S., Zhou L.-M., Hillyard D.R., Olivera B.M.
J. Biol. Chem. 273:5447-5450(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-85.
Tissue: Venom duct.
[2]"Gamma-carboxyglutamate in a neuroactive toxin."
McIntosh J.M., Olivera B.M., Cruz L.J., Gray W.R.
J. Biol. Chem. 259:14343-14346(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 81-97, AMIDATION AT ASN-97, GAMMA-CARBOXYGLUTAMATION AT GLU-83; GLU-84; GLU-87; GLU-90 AND GLU-94.
[3]"Diversity of Conus neuropeptides."
Olivera B.M., Rivier J., Clark C., Ramilo C.A., Corpuz G.P., Abogadie F.C., Mena E.E., Woodward S.R., Hillyard D.R., Cruz L.J.
Science 249:257-263(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"The amino acid residue at sequence position 5 in the conantokin peptides partially governs subunit-selective antagonism of recombinant N-methyl-D-aspartate receptors."
Klein R.C., Prorok M., Galdzicki Z., Castellino F.J.
J. Biol. Chem. 276:26860-26867(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-85, SITE.
[5]"Binding of cations to individual gamma-carboxyglutamate residues of conantokin-G and conantokin-T."
Blandl T., Warder S.E., Prorok M., Castellino F.J.
J. Pept. Res. 53:453-464(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: METAL-BINDING.
[6]"Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T."
Malmberg A.B., Gilbert H., McCabe R.T., Basbaum A.I.
Pain 101:109-116(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: THERAPEUTIC USAGE.
[7]"Three-dimensional structure of a gamma-carboxyglutamic acid-containing conotoxin, conantokin G, from the marine snail Conus geographus: the metal-free conformer."
Rigby A.C., Baleja J.D., Furie B.C., Furie B.
Biochemistry 36:6906-6914(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 81-97.
[8]"Role of gamma-carboxyglutamic acid in the calcium-induced structural transition of conantokin G, a conotoxin from the marine snail Conus geographus."
Rigby A.C., Baleja J.D., Li L., Pedersen L.G., Furie B.C., Furie B.
Biochemistry 36:15677-15684(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 81-97.
[9]"Determination of the solution structures of conantokin-G and conantokin-T by CD and NMR spectroscopy."
Skjaerbaek N., Nielsen K.J., Lewis R.J., Alewood P.F., Craik D.J.
J. Biol. Chem. 272:2291-2299(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 81-97.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF043141 mRNA. Translation: AAC15669.1.
PIRA05168.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AD7NMR-A81-97[»]
1AWYNMR-A81-97[»]
1ONUNMR-A81-97[»]
2DPQX-ray1.25A81-97[»]
ProteinModelPortalP07231.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

ConoServer1373. Conantokin-G precursor.
1353. Conantokin-G precursor (variant).

Family and domain databases

InterProIPR005918. Conantokin_CS.
[Graphical view]
PROSITEPS60025. CONANTOKIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP07231.

Entry information

Entry nameCKG_CONGE
AccessionPrimary (citable) accession number: P07231
Secondary accession number(s): O61475
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: December 15, 1998
Last modified: May 14, 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