P0C1Z0 (TXFA2_DENAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Fasciculin-2 Short name=Fas-2 Short name=Fas2 Alternative name(s): Acetylcholinesterase toxin F-VII Fasciculin-II Short name=FAS-II Toxin TA1
Organism	Dendroaspis angusticeps (Eastern green mamba)
Taxonomic identifier	8618 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Elapidae › Elapinae › Dendroaspis

Protein attributes

Sequence length	61 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This three-finger toxin selectively binds and inhibits with a 1:1 stoichiometry the mammalian and electric fish acetylcholinesterase (AChE) at picomolar concentrations. It is highly specific for the peripheral site on acetylcholinesterase. It has been called fasciculin since after injection into mice it cause severe, generalized and long-lasting (5-7 hours) fasciculations. The whole venom has anticoagulant activity, and the various components seem to act synergistically.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Toxic dose	LD50 is >20 mg/kg by intravenous injection.
Sequence similarities	Belongs to the snake three-finger toxin family. Acn-esterase inhibitor subfamily.

Ontologies

Keywords
Cellular component	Secreted
Molecular function	Toxin
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	modification of morphology or physiology of other organism Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 61

61

Fasciculin-2

PRO_0000253031

Sites

Site

27

1

May interact with AChE

Site

30

1

May interact with AChE

Site

31

1

May interact with AChE

Amino acid modifications

Disulfide bond

3 ↔ 22

Ref.5 Ref.6 Ref.7

Disulfide bond

17 ↔ 39

Ref.5 Ref.6 Ref.7

Disulfide bond

41 ↔ 52

Ref.5 Ref.6 Ref.7

Disulfide bond

53 ↔ 59

Ref.5 Ref.6 Ref.7

Experimental info

Mutagenesis

8 – 9

2

TT → AA: 18-fold increase in inhibition potency.

Mutagenesis

11

1

R → Q: 6-fold increase in inhibition potency. Ref.3

Mutagenesis

24

1

R → T: 13-fold decrease in inhibition potency. Ref.3

Mutagenesis

25

1

K → L: No significant difference in inhibition potency. Ref.3

Mutagenesis

27

1

R → W: 49-fold decrease in inhibition potency. Ref.3

Mutagenesis

28

1

R → D: No significant difference in inhibition potency. Ref.3

Mutagenesis

29

1

H → D: 73-fold increase in inhibition potency. Ref.3

Mutagenesis

30

1

Missing: 192-fold decrease in inhibition potency. Ref.3

Mutagenesis

31

1

P → R: 625-fold decrease in inhibition potency. Ref.3

Mutagenesis

32

1

K → G: 3-fold decrease in inhibition potency. Ref.3

Mutagenesis

33

1

M → A: 8-fold decrease in inhibition potency. Ref.3

Mutagenesis

34 – 35

2

VL → AA: No significant difference in inhibition potency.

Mutagenesis

45

1

D → K: No significant difference in inhibition potency. Ref.3

Mutagenesis

51

1

K → S: No significant difference in inhibition potency. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

61

Helix Strand Turn

Details...

Beta strand

2 – 4

3

Beta strand

6 – 9

4

Beta strand

14 – 16

3

Turn

18 – 19

2

Beta strand

22 – 31

10

Beta strand

34 – 40

7

Beta strand

46 – 53

8

Turn

57 – 60

4

Sequences

	Sequence		Length	Mass (Da)
	P0C1Z0 [UniParc]. Last modified October 17, 2006. Version 1. Checksum: 50A38EF3633C383F	FASTA	61	6,758
	10 20 30 40 50 60 TMCYSHTTTS RAILTNCGEN SCYRKSRRHP PKMVLGRGCG CPPGDDNLEV KCCTSPDKCN Y

References

[1]	"Snake venom toxins. The purification and amino acid sequence of toxin F-VII from Dendroaspis angusticeps venom." Viljoen C.C., Botes D.P. J. Biol. Chem. 248:4915-4919(1973) [PubMed: 4123919] [Abstract] Cited for: PROTEIN SEQUENCE. Tissue: Venom.
[2]	"Fasciculins, anticholinesterase toxins from the venom of the green mamba Dendroaspis angusticeps." Karlsson E., Mbugua P.M., Rodriguez-Ithurralde D. J. Physiol. (Paris) 79:232-240(1984) [PubMed: 6530667] [Abstract] Cited for: CHARACTERIZATION.
[3]	"Expression and activity of mutants of fasciculin, a peptidic acetylcholinesterase inhibitor from mamba venom." Marchot P., Prowse C.N., Kanter J., Camp S., Ackermann E.J., Radic Z., Bougis P.E., Taylor P. J. Biol. Chem. 272:3502-3510(1997) [PubMed: 9013597] [Abstract] Cited for: SYNTHESIS, MUTAGENESIS OF 8-THR-THR-9; ARG-11; ARG-24; LYS-25; ARG-27; ARG-28; HIS-29; PRO-30; PRO-31; LYS-32; MET-33; 34-VAL-LEU-35; ASP-45 AND LYS-51.
[4]	"Crystals of fasciculin 2 from green mamba snake venom. Preparation and preliminary X-ray analysis." le Du M.H., Marchot P., Bougis P.E., Fontecilla-Camps J.-C. J. Biol. Chem. 264:21401-21402(1989) [PubMed: 2592383] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS).
[5]	"Structure of fasciculin 2 from green mamba snake venom: evidence for unusual loop flexibility." le Du M.-H., Housset D., Marchot P., Bougis P.E., Navaza J., Fontecilla-Camps J.-C. Acta Crystallogr. D 52:87-92(1996) [PubMed: 15299729] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), DISULFIDE BONDS.
[6]	"Crystal structure of an acetylcholinesterase-fasciculin complex: interaction of a three-fingered toxin from snake venom with its target." Harel M., Kleywegt G.J., Ravelli R.B., Silman I., Sussman J.L. Structure 3:1355-1366(1995) [PubMed: 8747462] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF COMPLEX WITH ACHE, DISULFIDE BONDS.
[7]	"Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex." Bourne Y., Taylor P., Marchot P. Cell 83:503-512(1995) [PubMed: 8521480] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF COMPLEX WITH ACHE, DISULFIDE BONDS.
[8]	"Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II." Kryger G., Harel M., Giles K., Toker L., Velan B., Lazar A., Kronman C., Barak D., Ariel N., Shafferman A., Silman I., Sussman J.L. Acta Crystallogr. D 56:1385-1394(2000) [PubMed: 11053835] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS).
[9]	"Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site." Bourne Y., Taylor P., Radic Z., Marchot P. EMBO J. 22:1-12(2003) [PubMed: 12505979] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

PIR

T4EP1A. A01674.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B41	X-ray	2.76	B	1-61	[»]
1F8U	X-ray	2.90	B	1-61	[»]
1FSC	X-ray	2.00	A	1-61	[»]
1FSS	X-ray	3.00	B	1-61	[»]
1KU6	X-ray	2.50	B	1-61	[»]
1MAH	X-ray	3.20	F	1-61	[»]
2X8B	X-ray	2.95	B	1-61	[»]

ProteinModelPortal

P0C1Z0.

SMR

P0C1Z0. Positions 1-61.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

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Phylogenomic databases

HOVERGEN

HBG006553.

Family and domain databases

InterPro

IPR003571. Snake_toxin.
IPR018354. Snake_toxin_BS.
[Graphical view]

Pfam

PF00087. Toxin_1. 1 hit.
[Graphical view]

PROSITE

PS00272. SNAKE_TOXIN. 1 hit.
[Graphical view]

ProtoNet

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Entry information

Entry name

TXFA2_DENAN

Accession

Primary (citable) accession number: P0C1Z0
Secondary accession number(s): P01403

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 17, 2006
Last modified:	December 14, 2011
This is version 30 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Annotation program

Chordata Protein Annotation Program