P45639 (SCXL_LEIQU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Chlorotoxin Short name=CTX Short name=ClTx
Organism	Leiurus quinquestriatus quinquestriatus (Egyptian scorpion)
Taxonomic identifier	6885 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Protostomia › Ecdysozoa › Panarthropoda › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Leiurus › Leiurus quinquestriatus

Protein attributes

Sequence length	36 AA.
Sequence status	Complete.
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 Ion channel impairing toxin Neurotoxin Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing Pharmaceutical
Gene Ontology (GO)
Biological_process	pathogenesis Inferred from electronic annotation. Source: InterPro
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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.

Web resources

Wikipedia

Chlorotoxin entry

Cross-references

Sequence databases

PIR

A48850.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P45639.

SMR

P45639. Positions 1-36.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR003614. Scorpion_toxin-like.
IPR007958. Scorpion_toxinS_Cl_inh.
[Graphical view]

Pfam

PF05294. Toxin_5. 1 hit.
[Graphical view]

SUPFAM

SSF57095. SSF57095. 1 hit.

PROSITE

PS51200. SHORT_SCORPION_CHLORIDE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P45639.

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:	May 1, 2013
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program