Reviewed, UniProtKB/Swiss-Prot P45639 (SCXL_LEIQU)

Names and origin

Protein names	Recommended name:     Chlorotoxin       Short name=CTX
Organism	Leiurus quinquestriatus quinquestriatus (Egyptian scorpion)
Taxonomic identifier	6885 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Leiurus

Protein attributes

Sequence length	36 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Chloride channel ligand. Blocks small-conductance chloride channels.
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.
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.
Sequence similarities	Belongs to the short scorpion toxin superfamily. Chloride channel inhibitor family.

Ontologies

Keywords
Cellular component	Secreted
Domain	Knottin
Molecular function	Chloride channel inhibitor Ionic channel inhibitor Neurotoxin Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological process	pathogenesis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	chloride channel inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Peptide

1 – 36

36

Chlorotoxin

PRO_0000044941

Amino acid modifications

Disulfide bond

2 ↔ 19

Ref.4

Disulfide bond

5 ↔ 28

Ref.4

Disulfide bond

16 ↔ 33

Ref.4

Disulfide bond

20 ↔ 35

Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

36

Helix Strand Turn

Details...

Beta strand

9 – 12

4

Helix

13 – 20

8

Beta strand

22 – 25

4

Beta strand

27 – 29

3

Beta strand

32 – 34

3

Sequences

	Sequence		Length	Mass (Da)
	P45639-1 [UniParc]. Last modified November 1, 1995. Version 1. Checksum: 14A9F57559C6E92A	FASTA	36	4,005
	10 20 30 MCMPCFTTDH QMARKCDDCC GGKGRGKCYG PQCLCR

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: 8383429] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Venom.
[2]	"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: 9809993] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE.
[3]	"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: 16877732] [Abstract] Cited for: POTENTIAL THERAPEUTIC USAGE IN TREATMENT OF GLIOMA.
[4]	"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: 7819188] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Cross-references

Sequence databases

PIR

A48850.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CHL	NMR	-	A	1-36	[»]

ModBase

Search...

Family and domain databases

InterPro

IPR007958. Toxin_5.
[Graphical view]

Pfam

PF05294. Toxin_5. 1 hit.
[Graphical view]

PROSITE

PS51200. SHORT_SCORPION_CHLORIDE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

SCXL_LEIQU

Accession

Primary (citable) accession number: P45639

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	June 16, 2009
This is version 55 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Tox-Prot (Toxin Annotation Project)