P01484 (SCX2_ANDAU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Alpha-mammal toxin AaH2 Alternative name(s): AaH II Short name=AaHII Neurotoxin 2
Organism	Androctonus australis (Sahara scorpion)
Taxonomic identifier	6858 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Arthropoda › Chelicerata › Arachnida › Scorpiones › Buthida › Buthoidea › Buthidae › Androctonus

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 and inhibit the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Post-translational modification	The amidation of His-83 is not necessary for toxicity.
Toxic dose	LD50 is 25 ng/kg by intracerebroventricular injection into mice, and LD50 is 11 µg/kg by subcutaneous injection. Ref.4
Miscellaneous	EC(50) is 2.6 nM on rat brain Nav1.2 (SCN2A) sodium channel. EC(50) is 2.2 nM on rat skeletal muscle Nav1.4 (SCN4A) sodium channel. The chimeric protein obtained (Ref.9) with the three mutants 27-Asp--Val-29, Gly-36 and 75-Arg--Arg-81 is termed chimera Aah2/Lqh-alpha-IT(27-29,36,75-81). This chimera was constructed so as to test the importance of critical residues of Lqh-alpha-IT.
Sequence similarities	Belongs to the long (4 C-C) scorpion toxin superfamily. Sodium channel inhibitor family. Alpha subfamily.
Mass spectrometry	Molecular mass is 7243.20 Da from positions 20 - 83. Determined by ESI. Ref.5

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Ionic channel inhibitor Neurotoxin Sodium channel inhibitor Toxin
PTM	Amidation Disulfide bond
Technical term	3D-structure 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	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 – 83

64

Alpha-mammal toxin AaH2

PRO_0000035220

Amino acid modifications

Modified residue

83

1

Histidine amide

Disulfide bond

31 ↔ 82

Ref.3 Ref.7

Disulfide bond

35 ↔ 55

Ref.3 Ref.7

Disulfide bond

41 ↔ 65

Ref.3 Ref.7

Disulfide bond

45 ↔ 67

Ref.3 Ref.7

Experimental info

Mutagenesis

27 – 29

3

DDV → KNY: Active on insects, but not on mammals; when associated with F-36 and 75-P--K-81. Ref.9

Mutagenesis

36

1

G → F: Active on insects, but not on mammals; when associated with 27-K--Y-29 and 75-P--K-81. Ref.9

Mutagenesis

75 – 81

7

RTKGPGR → PIRVPGK: Active on insects, but not on mammals; when associated with 27-K--Y-29 and F-36. Ref.9

Mutagenesis

77

1

K → E, I or V: Loss of toxin toxicity; tested only without C-terminal amidation. Ref.5

Mutagenesis

83

1

H → HG: Little loss in toxicity; G-84 is not amidated. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

85

Helix Strand Turn

Details...

Beta strand

21 – 26

6

Helix

38 – 47

10

Beta strand

51 – 59

9

Beta strand

62 – 70

9

Sequences

	Sequence		Length	Mass (Da)
	P01484 [UniParc]. Last modified July 1, 1993. Version 3. Checksum: 1740CC6B98363768	FASTA	85	9,548
	10 20 30 40 50 60 MNYLVMISLA LLFVTGVESV KDGYIVDDVN CTYFCGRNAY CNEECTKLKG ESGYCQWASP 70 80 YGNACYCYKL PDHVRTKGPG RCHGR

References

[1]	"Precursors of Androctonus australis scorpion neurotoxins. Structures of precursors, processing outcomes, and expression of a functional recombinant toxin II." Bougis P.E., Rochat H., Smith L.A. J. Biol. Chem. 264:19259-19265(1989) [PubMed: 2808423] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Hector. Tissue: Venom gland.
[2]	"The amino-acid sequence of neurotoxin II of Androctonus australis hector." Rochat H., Rochat C., Sampieri F., Miranda F., Lissitzky S. Eur. J. Biochem. 28:381-388(1972) [PubMed: 4342910] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-82. Strain: Hector. Tissue: Venom.
[3]	"Disulfide bonds of toxin II of the scorpion Androctonus australis hector." Kopeyan C., Martinez G., Lissitzky S., Miranda F., Rochat H. Eur. J. Biochem. 47:483-489(1974) [PubMed: 4611766] [Abstract] Cited for: DISULFIDE BONDS. Strain: Hector.
[4]	"Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a new scorpion toxin that discriminates between neuronal and skeletal sodium channels." Alami M., Vacher H., Bosmans F., Devaux C., Rosso J.-P., Bougis P.E., Tytgat J., Darbon H., Martin-Eauclaire M.-F. Biochem. J. 375:551-560(2003) [PubMed: 12911331] [Abstract] Cited for: LETHAL DOSE, EFFECT CONCENTRATION. Tissue: Venom.
[5]	"Expression of the standard scorpion alpha-toxin AaH II and AaH II mutants leading to the identification of some key bioactive elements." Legros C., Ceard B., Vacher H., Marchot P., Bougis P.E., Martin-Eauclaire M.-F. Biochim. Biophys. Acta 1723:91-99(2005) [PubMed: 15725394] [Abstract] Cited for: MUTAGENESIS OF LYS-77 AND HIS-83, MASS SPECTROMETRY.
[6]	"Orthorhombic crystals and three-dimensional structure of the potent toxin II from the scorpion Androctonus australis Hector." Fontecilla-Camps J.-C., Habersetzer-Rochat C., Rochat H. Proc. Natl. Acad. Sci. U.S.A. 85:7443-7447(1988) [PubMed: 3174645] [Abstract] Cited for: CRYSTALLIZATION.
[7]	"Crystal structure of toxin II from the scorpion Androctonus australis hector refined at 1.3-A resolution." Housset D., Habersetzer-Rochat C., Astier J.-P., Fontecilla-Camps J.-C. J. Mol. Biol. 238:88-103(1994) [PubMed: 8145259] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS). Strain: Hector.
[8]	"Ab initio structure determination and refinement of a scorpion protein toxin." Smith G.D., Blessing R.H., Ealick S.E., Fontecilla-Camps J.-C., Hauptman H.A., Housset D., Langs D.A., Miller R. Acta Crystallogr. D 53:551-557(1997) [PubMed: 15299886] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (0.96 ANGSTROMS). Strain: Hector.
[9]	"Molecular basis of the high insecticidal potency of scorpion alpha-toxins." Karbat I., Frolow F., Froy O., Gilles N., Cohen L., Turkov M., Gordon D., Gurevitz M. J. Biol. Chem. 279:31679-31686(2004) [PubMed: 15133045] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 20-83 (CHIMERA AAH2/LQH-ALPHA-IT(27-29,36,75-81)), MUTAGENESIS OF 27-ASP--VAL-29; GLY-36 AND 75-ARG--ARG-81. Strain: Hector.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M27704 mRNA. Translation: AAA29949.1.

PIR

NTSR2A. D34444.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AHO	X-ray	0.96	A	20-83	[»]
1PTX	X-ray	1.30	A	20-83	[»]
1SEG	X-ray	1.30	A	20-74	[»]

ProteinModelPortal

P01484.

SMR

P01484. Positions 20-83.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR003614. Knot1.
IPR001219. Neurotoxin.
IPR018218. Scorpion_toxin.
IPR002061. Scorpion_toxin_lc.
[Graphical view]

Pfam

PF00537. Toxin_3. 1 hit.
[Graphical view]

PRINTS

PR00285. SCORPNTOXIN.
PR00284. TOXIN.

SMART

SM00505. Knot1. 1 hit.
[Graphical view]

ProtoNet

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Entry information

Entry name

SCX2_ANDAU

Accession

Primary (citable) accession number: P01484

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	July 1, 1993
Last modified:	November 16, 2011
This is version 94 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program