P17728 (SCXA_LEIQH) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Alpha-insect toxin LqhaIT Alternative name(s): Lqh-alpha-IT Short name=Alpha-IT
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	85 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	Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. The dissociation is voltage-dependent. This toxin is active on insects. It is also highly toxic to crustaceans and has a measurable but low toxicity to mice.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Toxic dose	LD50 is 250 µg/kg by subcutaneous injection to mice. Ref.3
Miscellaneous	The binding sites for this contractive toxin differ from those shared by the excitatory and depressant insect toxins.
Sequence similarities	Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.
Caution	The mutagenesis studies described in Ref.3 and Ref.4 are made with the sequence from Ref.2 (see the sequence conflict in position 83-85).

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Ion channel impairing toxin Neurotoxin Sodium channel inhibitor Toxin
PTM	Disulfide bond
Technical term	3D-structure 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 – 19

19

Ref.2

Chain

20 – 85

66

Alpha-insect toxin LqhaIT

PRO_0000035296

Amino acid modifications

Disulfide bond

31 ↔ 82

Ref.7

Disulfide bond

35 ↔ 55

Ref.7

Disulfide bond

41 ↔ 65

Ref.7

Disulfide bond

45 ↔ 67

Ref.7

Experimental info

Mutagenesis

27

1

K → A: 74% loss of toxicity and 39.4-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

27

1

K → D: 99.4% loss of toxicity and 1611-fold decrease in affinity to cockroach neuronal receptor. 95% loss of toxicity and 71.4-fold decrease in affinity to cockroach neuronal receptor; when associated with A-34. 99.6% loss of toxicity and 21303-fold decrease in affinity to cockroach neuronal receptor; when associated with D-28 and V-29. Ref.4

Mutagenesis

28

1

N → D: 99.6% loss of toxicity and 21303-fold decrease in affinity to cockroach neuronal receptor; when associated with D-27 and V-29.

Mutagenesis

29

1

Y → S: 90% loss of toxicity and 114.3-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

29

1

Y → V: 99.6% loss of toxicity and 21303-fold decrease in affinity to cockroach neuronal receptor; when associated with D-27 and D-28. Ref.4

Mutagenesis

29

1

Y → W: 57% loss of toxicity and 3.7-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

34

1

E → A: 77% loss of toxicity and 0.6-fold decrease in affinity to cockroach neuronal receptor; 95% loss of toxicity and 71.4-fold decrease in affinity to cockroach neuronal receptor; when associated with D-27. Ref.4

Mutagenesis

36

1

F → G: 86% loss of toxicity and 160-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

37

1

R → A: 78% loss of toxicity and 231.4-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

37

1

R → K: 59% loss of toxicity and 0.46-fold decrease in affinity to cockroach neuronal receptor; when associated with N-38. Ref.4

Mutagenesis

38

1

D → H: 75% loss of toxicity and 6-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

38

1

D → N: 15% increase in toxicity and 1.2-fold decrease in affinity to cockroach neuronal receptor; 59% loss of toxicity and 0.46-fold decrease in affinity to cockroach neuronal receptor; when associated with K-37. Ref.4

Mutagenesis

59

1

G → S: 36% loss of toxicity and 25.7-fold decrease in affinity to cockroach neuronal receptor; when associated with P-60.

Mutagenesis

60

1

K → P: 36% loss of toxicity and 25.7-fold decrease in affinity to cockroach neuronal receptor; when associated with S-59.

Mutagenesis

68

1

Y → I: 20% loss of toxicity to mice and 1.18-fold decrease in affinity to locust synaptosomal membranes; when associated with K-69. 540% loss of toxicity to mice and 1.08-fold decrease in affinity to locust synaptosomal membranes; when associated with K-69 and K-73. Ref.3

Mutagenesis

69

1

A → K: 20% loss of toxicity to mice and 1.18-fold decrease in affinity to locust synaptosomal membranes; when associated with I-68. 540% loss of toxicity to mice and 1.08-fold decrease in affinity to locust synaptosomal membranes; when associated with I-68 and K-73. Ref.3

Mutagenesis

73

1

N → K: 540% loss of toxicity to mice and 1.08-fold decrease in affinity to locust synaptosomal membranes; when associated with I-68 and K-69. Ref.3

Mutagenesis

81

1

K → L: 81% loss of toxicity and 220-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

84

1

R → A: 47% decrease in toxicity and 54.3-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

84

1

R → D: 95% decrease in toxicity and 2394-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

84

1

R → H: 220% decrease in toxicity and 0.3-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Mutagenesis

84

1

R → N: 6% increase in toxicity and 58.6-fold decrease in affinity to cockroach neuronal receptor. Ref.4

Sequence conflict

83 – 85

3

HRK → R AA sequence Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

85

Helix Strand Turn

Details...

Beta strand

20 – 27

8

Turn

28 – 30

3

Helix

38 – 47

10

Beta strand

51 – 59

9

Beta strand

62 – 71

10

Sequences

	Sequence		Length	Mass (Da)
	P17728 [UniParc]. Last modified March 1, 1992. Version 2. Checksum: 3338BED532D53FA7	FASTA	85	9,571
	10 20 30 40 50 60 MNHLVMISLA LLLLLGVESV RDAYIAKNYN CVYECFRDAY CNELCTKNGA SSGYCQWAGK 70 80 YGNACWCYAL PDNVPIRVPG KCHRK

References

[1]	"Nucleotide sequence and structure analysis of a cDNA encoding an alpha insect toxin from the scorpion Leiurus quinquestriatus hebraeus." Gurevitz M., Urbach D., Zlotkin E., Zilberberg N. Toxicon 29:1270-1272(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[2]	"A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure, and mode of action." Eitan M., Fowler E., Herrmann R., Duval A., Pelhate M., Zlotkin E. Biochemistry 29:5941-5947(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-85. Tissue: Venom.
[3]	"Functional expression and genetic alteration of an alpha scorpion neurotoxin." Zilberberg N., Gordon D., Pelhate M., Adams M.E., Norris T.M., Zlotkin E., Gurevitz M. Biochemistry 35:10215-10222(1996) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-68; ALA-69 AND ASN-73, LETHAL DOSE.
[4]	"Identification of structural elements of a scorpion alpha-neurotoxin important for receptor site recognition." Zilberberg N., Froy O., Loret E., Cestele S., Arad D., Gordon D., Gurevitz M. J. Biol. Chem. 272:14810-14816(1997) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-27; 27-LYS--TYR-29; 27-LYS--GLU-34; TYR-29; GLU-34; PHE-36; ARG-37; ASP-38; 37-ARG-ASP-38; 59-GLY-LYS-60; LYS-81 AND ARG-84.
[5]	"Modulation of cloned skeletal muscle sodium channels by the scorpion toxins Lqh II, Lqh III, and Lqh alphaIT." Chen H., Gordon D., Heinemann S.H. Pflugers Arch. 439:423-432(2000) [PubMed] [Europe PMC] [Abstract] Cited for: ELECTROPHYSIOLOGICAL CHARACTERIZATION.
[6]	"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.
[7]	"Solution structures of a highly insecticidal recombinant scorpion alpha-toxin and a mutant with increased activity." Tugarinov V., Kustanovich I., Zilberberg N., Gurevitz M., Anglister J. Biochemistry 36:2414-2424(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 20-82, DISULFIDE BONDS.

Cross-references

Sequence databases

PIR

A39306.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LQH	NMR	-	A	20-82	[»]
1LQI	NMR	-	A	20-82	[»]
2ASC	X-ray	1.10	A	20-82	[»]
2ATB	X-ray	1.60	A/B	20-82	[»]
2YEO	X-ray	1.08	A	20-82	[»]

ProteinModelPortal

P17728.

SMR

P17728. Positions 20-82.

ModBase

Search...

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...

Other

EvolutionaryTrace

P17728.

Entry information

Entry name

SCXA_LEIQH

Accession

Primary (citable) accession number: P17728

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	March 1, 1992
Last modified:	May 1, 2013
This is version 98 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program