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P07231

- CKG_CONGE

UniProt

P07231 - CKG_CONGE

Protein

Conantokin-G

Gene
N/A
Organism
Conus geographus (Geography cone) (Nubecula geographus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. Functioni

    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.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei85 – 851Important for selectivity
    Metal bindingi90 – 901Divalent metal cation; via 4-carboxyglutamate
    Metal bindingi94 – 941Divalent metal cation; via 4-carboxyglutamate

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW

    Keywords - Molecular functioni

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

    Keywords - Ligandi

    Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Conantokin-G
    Short name:
    Con-G
    Alternative name(s):
    CGX-1007
    Conotoxin GV
    Sleeper peptide
    OrganismiConus geographus (Geography cone) (Nubecula geographus)
    Taxonomic identifieri6491 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaLophotrochozoaMolluscaGastropodaCaenogastropodaHypsogastropodaNeogastropodaConoideaConidaeConus

    Organism-specific databases

    ConoServeri1373. Conantokin-G precursor.
    1353. Conantokin-G precursor (variant).

    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 under the name CGX-1007 by Cognetix Inc. to treat convulsion and epilepsy.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi85 – 851L → I: No loss of inhibition of NR1a/NR2B receptor; no inhibition of NR1a/NR2A receptor (as for the wild-type). 1 Publication
    Mutagenesisi85 – 851L → V: No loss of inhibition of NR1a/NR2B receptor; no inhibition of NR1a/NR2A receptor (as for the wild-type). 1 Publication
    Mutagenesisi85 – 851L → Y: Little loss of inhibition of NR1a/NR2B receptor; 70% of inhibition of NR1a/NR2A receptor. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2121Add
    BLAST
    Propeptidei22 – 8059PRO_0000035060Add
    BLAST
    Peptidei81 – 9717Conantokin-GPRO_0000035061Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei83 – 8314-carboxyglutamate1 Publication
    Modified residuei84 – 8414-carboxyglutamate1 Publication
    Modified residuei87 – 8714-carboxyglutamate1 Publication
    Modified residuei90 – 9014-carboxyglutamate1 Publication
    Modified residuei94 – 9414-carboxyglutamate1 Publication
    Modified residuei97 – 971Asparagine amide1 Publication

    Keywords - PTMi

    Amidation, Cleavage on pair of basic residues, Gamma-carboxyglutamic acid

    Expressioni

    Tissue specificityi

    Expressed by the venom duct.

    Structurei

    Secondary structure

    1
    100
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi82 – 9615

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1AD7NMR-A81-97[»]
    1AWYNMR-A81-97[»]
    1ONUNMR-A81-97[»]
    2DPQX-ray1.25A81-97[»]
    ProteinModelPortaliP07231.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP07231.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni61 – 8020Gamma-carboxylation recognition sequence that plays a role in the conversion of Glu to carboxy-Glu (Gla)CuratedAdd
    BLAST

    Sequence similaritiesi

    Belongs to the conotoxin B superfamily.Curated

    Keywords - Domaini

    Signal

    Family and domain databases

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

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P07231-1 [UniParc]FASTAAdd to Basket

    « Hide

    MHLYTYLYLL VPLVTFHLIL GTGTLDDGGA LTERRSADAT ALKAEPVLLQ    50
    KSAARSTDDN GKDRLTQMKR ILKQRGNKAR GEEELQENQE LIREKSNGKR 100
    Length:100
    Mass (Da):11,267
    Last modified:December 15, 1998 - v2
    Checksum:i3B0050FDFF2B9DFB
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti85 – 851L → V.1 Publication

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF043141 mRNA. Translation: AAC15669.1.
    PIRiA05168.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF043141 mRNA. Translation: AAC15669.1 .
    PIRi A05168.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AD7 NMR - A 81-97 [» ]
    1AWY NMR - A 81-97 [» ]
    1ONU NMR - A 81-97 [» ]
    2DPQ X-ray 1.25 A 81-97 [» ]
    ProteinModelPortali P07231.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    ConoServeri 1373. Conantokin-G precursor.
    1353. Conantokin-G precursor (variant).

    Miscellaneous databases

    EvolutionaryTracei P07231.

    Family and domain databases

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

    Publicationsi

    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. 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.

    Entry informationi

    Entry nameiCKG_CONGE
    AccessioniPrimary (citable) accession number: P07231
    Secondary accession number(s): O61475
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1988
    Last sequence update: December 15, 1998
    Last modified: October 1, 2014
    This is version 99 of the entry and version 2 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, 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