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P17684

- CKT_CONTU

UniProt

P17684 - CKT_CONTU

Protein

Conantokin-T

Gene
N/A
Organism
Conus tulipa (Fish-hunting cone snail) (Tulip cone)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli
  1. 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

    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

    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 – 2018

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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

    GEEEYQKMLE NLREAEVKKN A                                  21
    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:
    PDBe
    RCSB PDB
    PDBj
    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: October 1, 2014
    This is version 78 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