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P17684

- CKT_CONTU

UniProt

P17684 - CKT_CONTU

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Protein

Conantokin-T

Gene
N/A
Organism
Conus tulipa (Fish-hunting cone snail) (Tulip cone)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei5 – 51Important for selectivity

GO - Biological processi

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

Keywords - Molecular functioni

Ion channel impairing toxin, Ionotropic glutamate receptor inhibitor, Neurotoxin, Postsynaptic neurotoxin, Toxin

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Conantokin-T
Short name:
Con-T
OrganismiConus tulipa (Fish-hunting cone snail) (Tulip cone)
Taxonomic identifieri6495 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

Organism-specific databases

ConoServeri1269. Conantokin-T.

Subcellular locationi

GO - Cellular componenti

  1. other organism postsynaptic membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

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

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi5 – 51Y → F: No loss of inhibition of NR1a/NR2B receptor; little loss of inhibition of NR1a/NR2A receptor. 1 Publication
Mutagenesisi5 – 51Y → V: Little loss of inhibition of NR1a/NR2B receptor; important loss of inhibition of NR1a/NR2A receptor. 1 Publication
Mutagenesisi5 – 51Y → W: Little loss of inhibition of NR1a/NR2B receptor; complete loss of inhibition of NR1a/NR2A receptor. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Peptidei1 – 2121Conantokin-TPRO_0000044504Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei3 – 314-carboxyglutamate1 Publication
Modified residuei4 – 414-carboxyglutamate1 Publication
Modified residuei10 – 1014-carboxyglutamate1 Publication
Modified residuei14 – 1414-carboxyglutamate1 Publication
Modified residuei21 – 211Alanine amide1 Publication

Keywords - PTMi

Amidation, Gamma-carboxyglutamic acid

Expressioni

Tissue specificityi

Expressed by the venom duct.

Structurei

Secondary structure

1
21
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi3 – 2018Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ONTNMR-A1-21[»]
2DPRX-ray1.70A/B1-21[»]
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP17684.

Family & Domainsi

Sequence similaritiesi

Belongs to the conotoxin B superfamily.Curated

Family and domain databases

InterProiIPR005918. Conantokin_CS.
[Graphical view]
PfamiPF10550. Toxin_36. 1 hit.
[Graphical view]
PROSITEiPS60025. CONANTOKIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P17684-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20 
GEEEYQKMLE NLREAEVKKN A
Length:21
Mass (Da):2,509
Last modified:August 1, 1990 - v1
Checksum:i7F7B893AC4842C38
GO

Sequence databases

PIRiA35225.

Cross-referencesi

Sequence databases

PIRi A35225.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1ONT NMR - A 1-21 [» ]
2DPR X-ray 1.70 A/B 1-21 [» ]
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

ConoServeri 1269. Conantokin-T.

Miscellaneous databases

EvolutionaryTracei P17684.

Family and domain databases

InterProi IPR005918. Conantokin_CS.
[Graphical view ]
Pfami PF10550. Toxin_36. 1 hit.
[Graphical view ]
PROSITEi PS60025. CONANTOKIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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. 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.

Entry informationi

Entry nameiCKT_CONTU
AccessioniPrimary (citable) accession number: P17684
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: August 1, 1990
Last modified: November 26, 2014
This is version 80 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Miscellaneous

The mature peptide does not contain cysteine residue.

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

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