Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P17684 (CKT_CONTU) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 77. 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-T

Short name=Con-T
OrganismConus tulipa (Fish-hunting cone snail) (Tulip cone)
Taxonomic identifier6495 [NCBI]
Taxonomic lineageEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Protein attributes

Sequence length21 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin inhibits both NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor-mediated calcium influx in central nervous system neurons. Induces sleep-like symptoms in young mice and hyperactivity in older mice. Ref.2

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom duct.

Pharmaceutical use

Failed in phase II clinical trial. Was tested by Cognetix Inc. to treat antinociceptive effects in several models of injury-induced pain.

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

Peptide1 – 2121Conantokin-T
PRO_0000044504

Sites

Site51Important for selectivity

Amino acid modifications

Modified residue314-carboxyglutamate Ref.1
Modified residue414-carboxyglutamate Ref.1
Modified residue1014-carboxyglutamate Ref.1
Modified residue1414-carboxyglutamate Ref.1
Modified residue211Alanine amide Ref.1

Experimental info

Mutagenesis51Y → F: No loss of inhibition of NR1a/NR2B receptor; little loss of inhibition of NR1a/NR2A receptor. Ref.3
Mutagenesis51Y → V: Little loss of inhibition of NR1a/NR2B receptor; important loss of inhibition of NR1a/NR2A receptor. Ref.3
Mutagenesis51Y → W: Little loss of inhibition of NR1a/NR2B receptor; complete loss of inhibition of NR1a/NR2A receptor. Ref.3

Secondary structure

... 21
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P17684 [UniParc].

Last modified August 1, 1990. Version 1.
Checksum: 7F7B893AC4842C38

FASTA212,509
        10         20 
GEEEYQKMLE NLREAEVKKN A 

« Hide

References

[1]"Conantokin-T. A gamma-carboxyglutamate containing peptide with N-methyl-D-aspartate antagonist activity."
Haack J.A., Rivier J.E., Parks T.N., Mena E.E., Cruz L.J., Olivera B.M.
J. Biol. Chem. 265:6025-6029(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE, AMIDATION AT ALA-21, GAMMA-CARBOXYGLUTAMATION AT GLU-3; GLU-4; GLU-10 AND GLU-14.
Tissue: Venom.
[2]"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.
[3]"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 TYR-5, SITE.
[4]"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: PHARMACEUTICAL.
[5]"The NMR solution structure of the NMDA receptor antagonist, conantokin-T, in the absence of divalent metal ions."
Warder S.E., Chen Z., Zhu Y., Prorok M., Castellino F.J., Ni F.
FEBS Lett. 411:19-26(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[6]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

PIRA35225.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ONTNMR-A1-21[»]
2DPRX-ray1.70A/B1-21[»]
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

ConoServer1269. Conantokin-T.

Family and domain databases

InterProIPR005918. Conantokin_CS.
[Graphical view]
PfamPF10550. Toxin_36. 1 hit.
[Graphical view]
PROSITEPS60025. CONANTOKIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP17684.

Entry information

Entry nameCKT_CONTU
AccessionPrimary (citable) accession number: P17684
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: May 14, 2014
This is version 77 of the entry and version 1 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