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P56852

- TXHN1_GRARO

UniProt

P56852 - TXHN1_GRARO

Protein

Kappa-theraphotoxin-Gr1a

Gene
N/A
Organism
Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli
  1. Functioni

    Inhibits Kv2.1/KCNB1 and Kv4.2/KCND2 voltage-gated potassium channels. Acts as a gating modifier by shifting channel openings to more depolarized voltages and acts via the occupancy of multiple binding sites on the channel. The toxin binding sites are situated on the S3-S4 extracellular linker of the channel. At least two hanatoxin molecules can occupy the Kv2.1/KCNB1 channel, and maybe more (three or four). Can also inhibit calcium channels (Cav2.1/CACNA1A). Needs to partition into the membrane in order to bind to the channel.4 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei3 – 31May be involved in interaction with voltage sensorBy similarity
    Sitei22 – 221May be involved in interaction with voltage sensorBy similarity
    Sitei30 – 301Involved in active faceBy similarity

    GO - Molecular functioni

    1. ion channel inhibitor activity Source: InterPro

    GO - Biological processi

    1. pathogenesis Source: InterPro

    Keywords - Molecular functioni

    Calcium channel impairing toxin, Ion channel impairing toxin, Neurotoxin, Potassium channel impairing toxin, Toxin, Voltage-gated calcium channel impairing toxin, Voltage-gated potassium channel impairing toxin

    Protein family/group databases

    TCDBi8.B.5.3.6. the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Kappa-theraphotoxin-Gr1a
    Short name:
    Kappa-TRTX-Gr1a
    Alternative name(s):
    Hanatoxin-1
    Short name:
    HaTx1
    OrganismiGrammostola rosea (Chilean rose tarantula) (Grammostola spatulata)
    Taxonomic identifieri432528 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaAraneaeMygalomorphaeTheraphosidaeGrammostola

    Organism-specific databases

    ArachnoServeriAS000342. kappa-theraphotoxin-Gr1a.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Peptidei1 – 3535Kappa-theraphotoxin-Gr1aPRO_0000045012Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi2 ↔ 161 Publication
    Disulfide bondi9 ↔ 211 Publication
    Disulfide bondi15 ↔ 281 Publication

    Keywords - PTMi

    Disulfide bond

    Expressioni

    Tissue specificityi

    Expressed by the venom gland.

    Structurei

    Secondary structure

    1
    35
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi12 – 143
    Beta strandi17 – 215
    Turni23 – 253
    Beta strandi27 – 304

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1D1HNMR-A1-35[»]
    ProteinModelPortaliP56852.
    SMRiP56852. Positions 1-35.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP56852.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni4 – 63Involved in active faceBy similarity

    Domaini

    The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.

    Sequence similaritiesi

    Belongs to the huwentoxin-1 family.Curated

    Keywords - Domaini

    Knottin

    Family and domain databases

    InterProiIPR011696. Ion_channel_inhibitory.
    [Graphical view]
    PfamiPF07740. Toxin_12. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P56852-1 [UniParc]FASTAAdd to Basket

    « Hide

    ECRYLFGGCK TTSDCCKHLG CKFRDKYCAW DFTFS                   35
    Length:35
    Mass (Da):4,121
    Last modified:May 30, 2000 - v1
    Checksum:iD401AC8A9B14DB12
    GO

    Cross-referencesi

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1D1H NMR - A 1-35 [» ]
    ProteinModelPortali P56852.
    SMRi P56852. Positions 1-35.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    TCDBi 8.B.5.3.6. the na(+)/k(+)/ca(2+) channel targeting tarantula huwentoxin (tht) family.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    ArachnoServeri AS000342. kappa-theraphotoxin-Gr1a.

    Miscellaneous databases

    EvolutionaryTracei P56852.

    Family and domain databases

    InterProi IPR011696. Ion_channel_inhibitory.
    [Graphical view ]
    Pfami PF07740. Toxin_12. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula."
      Swartz K.J., MacKinnon R.
      Neuron 15:941-949(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE.
      Tissue: Venom.
    2. "Hanatoxin modifies the gating of a voltage-dependent K+ channel through multiple binding sites."
      Swartz K.J., MacKinnon R.
      Neuron 18:665-673(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    3. "Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels."
      Swartz K.J., MacKinnon R.
      Neuron 18:675-682(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    4. "Gating modifier toxins reveal a conserved structural motif in voltage-gated Ca2+ and K+ channels."
      Li-Smerin Y., Swartz K.J.
      Proc. Natl. Acad. Sci. U.S.A. 95:8585-8589(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    5. "Voltage-sensor activation with a tarantula toxin as cargo."
      Phillips L.R., Milescu M., Li-Smerin Y., Mindell J.A., Kim J.I., Swartz K.J.
      Nature 436:857-860(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: MEMBRANE-PARTITIONING.
    6. "Gating modifier peptides as probes of pancreatic beta-cell physiology."
      Herrington J.
      Toxicon 49:231-238(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION ON PANCREATIC BETA-CELLS.
    7. "Solution structure of hanatoxin1, a gating modifier of voltage-dependent K(+) channels: common surface features of gating modifier toxins."
      Takahashi H., Kim J.I., Min H.J., Sato K., Swartz K.J., Shimada I.
      J. Mol. Biol. 297:771-780(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

    Entry informationi

    Entry nameiTXHN1_GRARO
    AccessioniPrimary (citable) accession number: P56852
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 30, 2000
    Last modified: October 1, 2014
    This is version 64 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programAnimal Toxin Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    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