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P45639

- CTXL_LEIQU

UniProt

P45639 - CTXL_LEIQU

Protein

Chlorotoxin

Gene
N/A
Organism
Leiurus quinquestriatus quinquestriatus (Egyptian scorpion) (Deathstalker scorpion)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at protein leveli
  1. Functioni

    This toxin binds to the surface of glioma cells, and inhibits their proliferation without having effects on normal brain cells. In this context, this toxin has been described as a chloride channel inhibitor (probably ClC-3/CLCN3) by causing its internalization via caveolae (PubMed:16520829). It has also been described to selectively interact with MMP2 (in complex with MT1-MMP (MMP14) and TIMP2), to inhibit its enzymatic activity and to decrease its presence at the cell surface (PubMed:12454020).3 Publications

    GO - Molecular functioni

    1. chloride channel inhibitor activity Source: UniProtKB-KW
    2. metalloendopeptidase inhibitor activity Source: UniProtKB-KW

    GO - Biological processi

    1. defense response Source: InterPro
    2. pathogenesis Source: InterPro

    Keywords - Molecular functioni

    Chloride channel impairing toxin, Ion channel impairing toxin, Metalloenzyme inhibitor, Metalloprotease inhibitor, Neurotoxin, Protease inhibitor, Toxin, Voltage-gated chloride channel impairing toxin

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Chlorotoxin
    Short name:
    CTX
    Short name:
    ClTx
    OrganismiLeiurus quinquestriatus quinquestriatus (Egyptian scorpion) (Deathstalker scorpion)
    Taxonomic identifieri6885 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeLeiurus

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Biotechnological usei

    When bioconjugated with the fluorescent molecular beacon Cy5.5, might be used as an optical imaging contrast agent to enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue.1 Publication

    Pharmaceutical usei

    Is under phase II clinical trial by Sinai Medical Center and TransMolecular under the name TM-601. It crosses blood-brain and tissue barriers and binds to malignant brain tumor cells without affecting healthy tissue. Radioiodinated TM-601 is used to treat malignant glioma.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Peptidei1 – 3636ChlorotoxinPRO_0000044941Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi2 ↔ 191 PublicationPROSITE-ProRule annotation
    Disulfide bondi5 ↔ 281 PublicationPROSITE-ProRule annotation
    Disulfide bondi16 ↔ 331 PublicationPROSITE-ProRule annotation
    Disulfide bondi20 ↔ 351 PublicationPROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond

    Expressioni

    Tissue specificityi

    Expressed by the venom gland.

    Structurei

    Secondary structure

    1
    36
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi9 – 124
    Helixi13 – 208
    Beta strandi22 – 254
    Beta strandi27 – 293
    Beta strandi32 – 343

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CHLNMR-A1-36[»]
    ProteinModelPortaliP45639.
    SMRiP45639. Positions 1-36.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP45639.

    Family & Domainsi

    Domaini

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

    Sequence similaritiesi

    Belongs to the short scorpion toxin superfamily. Chloride channel inhibitor family.PROSITE-ProRule annotation

    Keywords - Domaini

    Knottin

    Family and domain databases

    InterProiIPR003614. Scorpion_toxin-like.
    IPR007958. Scorpion_toxinS_Cl_inh.
    [Graphical view]
    PfamiPF05294. Toxin_5. 1 hit.
    [Graphical view]
    SUPFAMiSSF57095. SSF57095. 1 hit.
    PROSITEiPS51200. SHORT_SCORPION_CHLORIDE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P45639-1 [UniParc]FASTAAdd to Basket

    « Hide

    MCMPCFTTDH QMARKCDDCC GGKGRGKCYG PQCLCR                  36
    Length:36
    Mass (Da):4,005
    Last modified:November 1, 1995 - v1
    Checksum:i14A9F57559C6E92A
    GO

    Sequence databases

    PIRiA48850.

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Chlorotoxin entry

    Sequence databases

    PIRi A48850.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1CHL NMR - A 1-36 [» ]
    ProteinModelPortali P45639.
    SMRi P45639. Positions 1-36.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Miscellaneous databases

    EvolutionaryTracei P45639.

    Family and domain databases

    InterProi IPR003614. Scorpion_toxin-like.
    IPR007958. Scorpion_toxinS_Cl_inh.
    [Graphical view ]
    Pfami PF05294. Toxin_5. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57095. SSF57095. 1 hit.
    PROSITEi PS51200. SHORT_SCORPION_CHLORIDE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion."
      Debin J.A., Maggio J.E., Strichartz G.R.
      Am. J. Physiol. 264:C361-C369(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE, FUNCTION.
      Tissue: Venom.
    2. "Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2."
      Deshane J., Garner C.C., Sontheimer H.
      J. Biol. Chem. 278:4135-4144(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS MMP-2 BINDING TOXIN.
    3. "A role for ion channels in glioma cell invasion."
      McFerrin M.B., Sontheimer H.
      Neuron Glia Biol. 2:39-49(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROBABLE FUNCTION AS CLC3 INHIBITOR, REVIEW.
    4. Cited for: BIOTECHNOLOGY.
    5. "Use of chlorotoxin for targeting of primary brain tumors."
      Soroceanu L., Gillespie Y., Khazaeli M.B., Sontheimer H.
      Cancer Res. 58:4871-4879(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHARMACEUTICAL.
    6. "Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma."
      Mamelak A.N., Rosenfeld S., Bucholz R., Raubitschek A., Nabors L.B., Fiveash J.B., Shen S., Khazaeli M.B., Colcher D., Liu A., Osman M., Guthrie B., Schade-Bijur S., Hablitz D.M., Alvarez V.L., Gonda M.A.
      J. Clin. Oncol. 24:3644-3650(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHARMACEUTICAL.
    7. "NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels."
      Lippens G., Najib J., Wodak S.J., Tartar A.
      Biochemistry 34:13-21(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

    Entry informationi

    Entry nameiCTXL_LEIQU
    AccessioniPrimary (citable) accession number: P45639
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 71 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programAnimal Toxin Annotation Program

    Miscellaneousi

    Miscellaneous

    Does not interact with MMP-1, MMP-3 and MMP-9.1 Publication

    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