P80670 (KAX83_LEIQH) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Toxin GaTx2 Alternative name(s): Gating modifier of anion channels 2 Leiuropeptide II Short name=LpII Leiuropeptide-2 Potassium channel toxin alpha-KTx 8.3
Organism	Leiurus quinquestriatus hebraeus (Yellow scorpion)
Taxonomic identifier	6884 [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	29 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Specific and potent inhibitor of ClC-2/CLCN2 chloride channel. It slows ClC-2/CLCN2 activation by increasing the latency to first opening by nearly 8-fold but is unable to inhibit open channels, suggesting that this toxin inhibits channel activation gating. Ref.2 Ref.3
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Miscellaneous	Does not inhibit ClC-0, ClC-1/CLCN1, ClC-3/CLCN3, ClC-4/CLCN4, CFTR chloride channel, GABRR, Cl(Ca), Shaker, and Kv1.2/KCNA2.
Sequence similarities	Belongs to the short scorpion toxin superfamily. Potassium channel inhibitor family. Alpha-KTx 8 subfamily.
Caution	Has sequence similarities with potassium channel inhibitors, but inhibits chloride channels. It is why the systematic name 'Potassium channel toxin alpha-KTx 8.3' has been moved as alternative name.
Mass spectrometry	Molecular mass is 3191.29 Da from positions 1 - 29. Determined by MALDI. Ref.2

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Chloride channel inhibitor Ion channel impairing toxin Toxin
PTM	Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological_process	defense response Inferred from electronic annotation. Source: InterPro 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 – 29	29	Toxin GaTx2		PRO_0000044542
Amino acid modifications
	Disulfide bond	3 ↔ 19		Ref.1
	Disulfide bond	6 ↔ 24		Ref.1
	Disulfide bond	10 ↔ 26		Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P80670 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: BC5F650C196C15B8	FASTA	29	3,199
	10 20 VSCEDCPDHC STQKARAKCD NDKCVCEPI

References

[1]	"Characterization of a new family of toxin-like peptides from the venom of the scorpion Leiurus quinquestriatus hebraeus. 1H-NMR structure of leiuropeptide II." Buisine E., Wieruszeski J.-M., Lippens G., Wouters D., Tartar A., Sautiere P. J. Pept. Res. 49:545-555(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, STRUCTURE BY NMR, DISULFIDE BONDS. Tissue: Venom.
[2]	"Isolation and characterization of a high affinity peptide inhibitor of ClC-2 chloride channels." Thompson C.H., Olivetti P.R., Fuller M.D., Freeman C.S., McMaster D., French R.J., Pohl J., Kubanek J., McCarty N.A. J. Biol. Chem. 284:26051-26062(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, SYNTHESIS, FUNCTION, TOXIN TARGET, MASS SPECTROMETRY. Tissue: Venom.
[3]	"Inhibition of ClC-2 chloride channels by a peptide component or components of scorpion venom." Thompson C.H., Fields D.M., Olivetti P.R., Fuller M.D., Zhang Z.R., Kubanek J., McCarty N.A. J. Membr. Biol. 208:65-76(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Moving pieces in a taxonomic puzzle: venom 2D-LC/MS and data clustering analyses to infer phylogenetic relationships in some scorpions from the Buthidae family (Scorpiones)." Nascimento D.G., Rates B., Santos D.M., Verano-Braga T., Barbosa-Silva A., Dutra A.A.A., Biondi I., Martin-Eauclaire M.-F., De Lima M.E., Pimenta A.M.C. Toxicon 47:628-639(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY.

Cross-references

3D structure databases
ProteinModelPortal	P80670.
SMR	P80670. Positions 1-29.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR003614. Scorpion_toxin-like. IPR008911. Toxin_6. [Graphical view]
Pfam	PF05453. Toxin_6. 1 hit. [Graphical view]
SUPFAM	SSF57095. SSF57095. 1 hit.
PROSITE	PS01138. SCORP_SHORT_TOXIN. False negative. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

KAX83_LEIQH

Accession

Primary (citable) accession number: P80670

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 29, 2013
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program