P19855 (SIX2_LEIQU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Beta-insect depressant toxin LqqIT2 Short name=Insect toxin 2
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	82 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Depressant insect beta-toxins cause a transient contraction paralysis followed by a slow flaccid paralysis. They bind voltage-independently at site-4 of sodium channels and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing. Aside from typical beta-toxin effects, this toxin also affects the inactivation process and ion selectivity of the insect voltage-gated sodium channel. This toxin is active only on insects. Is active on the insect voltage-gated sodium channel para, while its mammalian counterpart, the rat brain Nav1.2 (SCN2A) is not affected. Ref.5 Ref.6
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Sequence similarities	Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Beta subfamily.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Ion channel impairing toxin Neurotoxin Sodium channel inhibitor Toxin
PTM	Disulfide bond
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological_process	defense response Inferred from electronic annotation. Source: InterPro
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	sodium 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
	Signal peptide	1 – 21	21	Ref.2 Ref.3 Ref.4
	Chain	22 – 82	61	Beta-insect depressant toxin LqqIT2		PRO_0000035196
Amino acid modifications
	Disulfide bond	31 ↔ 81		By similarity
	Disulfide bond	35 ↔ 56		By similarity
	Disulfide bond	42 ↔ 63		By similarity
	Disulfide bond	46 ↔ 65		By similarity
Natural variations
	Natural variant	33	1	L → V.
	Natural variant	43	1	N → D.
	Natural variant	48	1	S → A.
	Natural variant	71	1	D → E.

Sequences

	Sequence		Length	Mass (Da)
	P19855 [UniParc]. Last modified October 24, 2003. Version 2. Checksum: F13D53B18CDECBF0	FASTA	82	9,100
	10 20 30 40 50 60 MKLLLLLIVS ASMLIESLVN ADGYIRKRDG CKLSCLFGNE GCNKECKSYG GSYGYCWTWG 70 80 LACWCEGLPD DKTWKSETNT CG

References

[1]	"Three polymorphic genes encoding a depressant toxin from the Egyptian scorpion Leiurus quinquestriatus quinquestriatus." Zaki T.I., Maruniak J.E. Toxicon 41:109-113(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Primary structure of scorpion anti-insect toxins isolated from the venom of Leiurus quinquestriatus quinquestriatus." Kopeyan C., Mansuelle P., Sampieri F., Brando T., Bahraoui E.M., Rochat H., Granier C. FEBS Lett. 261:423-426(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-82. Tissue: Venom.
[3]	"Functional duality and structural uniqueness of depressant insect-selective neurotoxins." Zlotkin E., Eitan M., Bindokas V.P., Adams M.E., Moyer M., Burkhart W., Fowler E. Biochemistry 30:4814-4821(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-82. Tissue: Venom.
[4]	"Depressant insect selective neurotoxins from scorpion venom: chemistry, action, and gene cloning." Zlotkin E., Gurevitz M., Fowler E., Adams M.E. Arch. Insect Biochem. Physiol. 22:55-73(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 22-82. Tissue: Venom.
[5]	"On the chemistry and action of the depressant insect toxins." Zlotkin E., Fowler E., Eitan M., Moyer M., Adams M.E. Toxicon 28:170-170(1990) Cited for: FUNCTION.
[6]	"The depressant scorpion neurotoxin LqqIT2 selectively modulates the insect voltage-gated sodium channel." Bosmans F., Martin-Eauclaire M.-F., Tytgat J. Toxicon 45:501-507(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION. Tissue: Venom.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF474983 mRNA. Translation: AAM74027.1. AF474984 mRNA. Translation: AAM74028.1. AF474985 mRNA. Translation: AAM74029.1.
PIR	B34123.
3D structure databases
ProteinModelPortal	P19855.
SMR	P19855. Positions 22-82.
ModBase	Search...
Protein family/group databases
TCDB	8.B.1.1.4. long (4C-C) scorpion toxin (L-ST) superfamily.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
Gene3D	3.30.30.10. 1 hit.
InterPro	IPR003614. Scorpion_toxin-like. IPR018218. Scorpion_toxinL. IPR002061. Scorpion_toxinL/defesin. [Graphical view]
Pfam	PF00537. Toxin_3. 1 hit. [Graphical view]
PRINTS	PR00285. SCORPNTOXIN.
SMART	SM00505. Knot1. 1 hit. [Graphical view]
SUPFAM	SSF57095. SSF57095. 1 hit.
ProtoNet	Search...

Entry information

Entry name

SIX2_LEIQU

Accession

Primary (citable) accession number: P19855
Secondary accession number(s): Q8MVS6, Q8MVS7, Q8MVS8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	October 24, 2003
Last modified:	May 1, 2013
This is version 77 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program