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P45639 (CTXL_LEIQU) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 70. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Chlorotoxin

Short name=CTX
Short name=ClTx
OrganismLeiurus quinquestriatus quinquestriatus (Egyptian scorpion) (Deathstalker scorpion)
Taxonomic identifier6885 [NCBI]
Taxonomic lineageEukaryotaMetazoaEcdysozoaArthropodaChelicerataArachnidaScorpionesButhidaButhoideaButhidaeLeiurus

Protein attributes

Sequence length36 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 (Ref.3). 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 (Ref.2). Ref.1 Ref.2 Ref.3

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom gland.

Domain

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

Biotechnological use

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. Ref.4

Pharmaceutical use

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.

Miscellaneous

Does not interact with MMP-1, MMP-3 and MMP-9 (Ref.2).

Sequence similarities

Belongs to the short scorpion toxin superfamily. Chloride channel inhibitor family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Peptide1 – 3636Chlorotoxin
PRO_0000044941

Amino acid modifications

Disulfide bond2 ↔ 19 Ref.7
Disulfide bond5 ↔ 28 Ref.7
Disulfide bond16 ↔ 33 Ref.7
Disulfide bond20 ↔ 35 Ref.7

Secondary structure

.......... 36
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P45639 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 14A9F57559C6E92A

FASTA364,005
        10         20         30 
MCMPCFTTDH QMARKCDDCC GGKGRGKCYG PQCLCR 

« Hide

References

[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]"Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci."
Veiseh M., Gabikian P., Bahrami S.B., Veiseh O., Zhang M., Hackman R.C., Ravanpay A.C., Stroud M.R., Kusuma Y., Hansen S.J., Kwok D., Munoz N.M., Sze R.W., Grady W.M., Greenberg N.M., Ellenbogen R.G., Olson J.M.
Cancer Res. 67:6882-6888(2007) [PubMed] [Europe PMC] [Abstract]
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.

Web resources

Wikipedia

Chlorotoxin entry

Cross-references

Sequence databases

PIRA48850.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CHLNMR-A1-36[»]
ProteinModelPortalP45639.
SMRP45639. Positions 1-36.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR003614. Scorpion_toxin-like.
IPR007958. Scorpion_toxinS_Cl_inh.
[Graphical view]
PfamPF05294. Toxin_5. 1 hit.
[Graphical view]
SUPFAMSSF57095. SSF57095. 1 hit.
PROSITEPS51200. SHORT_SCORPION_CHLORIDE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP45639.

Entry information

Entry nameCTXL_LEIQU
AccessionPrimary (citable) accession number: P45639
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 70 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references