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Protein

Chlorotoxin

Gene
N/A
Organism
Leiurus quinquestriatus quinquestriatus (Egyptian scorpion) (Deathstalker scorpion)
Status
Reviewed-Annotation score: -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

Miscellaneous

Does not interact with MMP-1, MMP-3 and MMP-9.1 Publication
Was tested in clinical trial under the name TM-601 for treatment of malignant glioma.1 Publication

GO - Molecular functioni

Keywordsi

Molecular functionChloride 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:
Chlorotoxin2 Publications
Short name:
CTX
Short name:
ClTx1 Publication
Alternative name(s):
INN: Tozuleristide
OrganismiLeiurus quinquestriatus quinquestriatus (Egyptian scorpion) (Deathstalker scorpion)
Taxonomic identifieri6885 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeLeiurus

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Biotechnological usei

Is under phase I clinical trial as BLZ-100 by Blaze Bioscience Inc. as a fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. BLZ-100 is composed of the chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PeptideiPRO_00000449411 – 36Chlorotoxin1 PublicationAdd BLAST36

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi2 ↔ 191 PublicationImported
Disulfide bondi5 ↔ 281 PublicationImported
Disulfide bondi16 ↔ 331 PublicationImported
Disulfide bondi20 ↔ 351 PublicationImported

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.1 Publication

Structurei

Secondary structure

136
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi2 – 4Combined sources3
Helixi12 – 20Combined sources9
Beta strandi22 – 25Combined sources4
Beta strandi26 – 29Combined sources4
Beta strandi32 – 35Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CHLNMR-A1-36[»]
5L1CNMR-A1-36[»]
6ATWX-ray1.53A1-36[»]
ProteinModelPortaliP45639
SMRiP45639
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP45639

Family & Domainsi

Domaini

The presence of a 'disulfide through disulfide knot' structurally defines this protein as a knottin.1 Publication

Sequence similaritiesi

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

Keywords - Domaini

Knottin

Family and domain databases

InterProiView protein in InterPro
IPR036574 Scorpion_toxin-like_sf
IPR007958 Scorpion_toxinS_Cl_inh
PfamiView protein in Pfam
PF05294 Toxin_5, 1 hit
SUPFAMiSSF57095 SSF57095, 1 hit
PROSITEiView protein in PROSITE
PS51200 SHORT_SCORPION_CHLORIDE, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiCTXL_LEIQU
AccessioniPrimary (citable) accession number: P45639
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: May 23, 2018
This is version 84 of the entry and version 1 of the sequence. See 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

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