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P45639

- CTXL_LEIQU

UniProt

P45639 - CTXL_LEIQU

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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

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. metalloendopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

  1. defense response Source: InterPro
  2. pathogenesis Source: InterPro
Complete GO annotation...

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-KW
Complete GO annotation...

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 – 124Combined sources
Helixi13 – 208Combined sources
Beta strandi22 – 254Combined sources
Beta strandi27 – 293Combined sources
Beta strandi32 – 343Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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

        10         20         30 
MCMPCFTTDH QMARKCDDCC GGKGRGKCYG PQCLCR
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:
PDBei
RCSB PDBi
PDBji
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 29, 2014
This is version 72 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