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P0C1Z0

- 3SE2_DENAN

UniProt

P0C1Z0 - 3SE2_DENAN

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Protein

Fasciculin-2

Gene
N/A
Organism
Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Interferes with neuromuscular transmission by inhibiting the enzyme acetylcholinesterase (AChE) present at the neuromuscular junction. It selectively binds and inhibits with a 1:1 stoichiometry the mammalian and electric fish AChE at picomolar concentrations. It is highly specific for the peripheral site of AChE and blocks the entry of acetylcholine into the active site of the enzyme (through the Met-33 residue), thereby preventing its breakdown. It has been called fasciculin since after injection into mice it causes severe, generalized and long-lasting (5-7 hours) fasciculations.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei33 – 331blocks the entrance of the active site gorge of hAChE1 Publication

GO - Biological processi

  1. modification of morphology or physiology of other organism Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Toxin

Names & Taxonomyi

Protein namesi
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
OrganismiDendroaspis angusticeps (Eastern green mamba) (Naja angusticeps)
Taxonomic identifieri8618 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeElapinaeDendroaspis

Subcellular locationi

Secreted 1 Publication

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Toxic dosei

LD50 is >20 mg/kg by intravenous injection.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi8 – 92TT → AA: 18-fold increase in inhibition potency. 1 Publication
Mutagenesisi8 – 81T → V: 2.5-fold increase in affinity for TcAChE. 2.1-fold decrease in affinity for TcAChE; when associated with N-9. 1.9-fold increase in affinity for TcAChE; when associated with N-9, K-11 and R-29 [FasDesK32]. 3.9-fold decrease in affinity for TcAChE; when associated with N-9, K-11, R-29 and R-32 [FasDes]. 1 Publication
Mutagenesisi9 – 91T → N: 9.0-fold decrease in affinity for TcAChE. 2.1-fold decrease in affinity for TcAChE; when associated with V-8. 1.9-fold increase in affinity for TcAChE; when associated with V-8, K-11 and R-29 [FasDesK32]. 3.9-fold decrease in affinity for TcAChE; when associated with V-8, K-11, R-29 and R-32 [FasDes]. 1 Publication
Mutagenesisi11 – 111R → K: 1.7-fold decrease in affinity for TcAChE. 1.9-fold increase in affinity for TcAChE; when associated with V-8, N-9 and R-29 [FasDesK32]. 3.9-fold decrease in affinity for TcAChE; when associated with V-8, N-9, R-29 and R-32 [FasDes]. 1 Publication
Mutagenesisi11 – 111R → Q: 6-fold increase in inhibition potency. 1 Publication
Mutagenesisi24 – 241R → T: 13-fold decrease in inhibition potency. 1 Publication
Mutagenesisi25 – 251K → L: No significant difference in inhibition potency. 1 Publication
Mutagenesisi27 – 271R → W: 49-fold decrease in inhibition potency. 1 Publication
Mutagenesisi28 – 281R → D: No significant difference in inhibition potency. 1 Publication
Mutagenesisi29 – 291H → D: 73-fold increase in inhibition potency. 1 Publication
Mutagenesisi29 – 291H → R: 6.0-fold increase in affinity for TcAChE. 1.9-fold increase in affinity for TcAChE; when associated with V-8, N-9 and K-11 [FasDesK32]. 3.9-fold decrease in affinity for TcAChE; when associated with V-8, N-9, K-11 and R-32 [FasDes]. 1 Publication
Mutagenesisi30 – 301Missing: 192-fold decrease in inhibition potency. 1 Publication
Mutagenesisi31 – 311P → R: 625-fold decrease in inhibition potency. 1 Publication
Mutagenesisi32 – 321K → G: 3-fold decrease in inhibition potency. 1 Publication
Mutagenesisi32 – 321K → R: 7.4-fold decrease in affinity for TcAChE. 3.9-fold decrease in affinity for TcAChE; when associated with V-8, N-9, K-11 and R-29 [FasDes]. 1 Publication
Mutagenesisi33 – 331M → A: 8-fold decrease in inhibition potency. 1 Publication
Mutagenesisi34 – 352VL → AA: No significant difference in inhibition potency. 1 Publication
Mutagenesisi45 – 451D → K: No significant difference in inhibition potency. 1 Publication
Mutagenesisi51 – 511K → S: No significant difference in inhibition potency. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 6161Fasciculin-2PRO_0000253031Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi3 ↔ 228 Publications
Disulfide bondi17 ↔ 398 Publications
Disulfide bondi41 ↔ 528 Publications
Disulfide bondi53 ↔ 598 Publications

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.Curated

Structurei

Secondary structure

1
61
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 65Combined sources
Beta strandi8 – 103Combined sources
Beta strandi13 – 164Combined sources
Beta strandi22 – 3110Combined sources
Beta strandi34 – 407Combined sources
Beta strandi46 – 538Combined sources
Turni57 – 604Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1B41X-ray2.76B1-61[»]
1F8UX-ray2.90B1-61[»]
1FSCX-ray2.00A1-61[»]
1FSSX-ray3.00B1-61[»]
1KU6X-ray2.50B1-61[»]
1MAHX-ray3.20F1-61[»]
2X8BX-ray2.95B1-61[»]
4BDTX-ray3.10B1-61[»]
4EY8X-ray2.60B1-61[»]
ProteinModelPortaliP0C1Z0.
SMRiP0C1Z0. Positions 1-61.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0C1Z0.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

HOVERGENiHBG006553.

Family and domain databases

InterProiIPR003571. Snake_toxin.
IPR018354. Snake_toxin_BS.
[Graphical view]
PfamiPF00087. Toxin_1. 1 hit.
[Graphical view]
PROSITEiPS00272. SNAKE_TOXIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0C1Z0-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
TMCYSHTTTS RAILTNCGEN SCYRKSRRHP PKMVLGRGCG CPPGDDNLEV
60
KCCTSPDKCN Y
Length:61
Mass (Da):6,758
Last modified:October 17, 2006 - v1
Checksum:i50A38EF3633C383F
GO

Sequence databases

PIRiA01674. T4EP1A.

Cross-referencesi

Sequence databases

PIRi A01674. T4EP1A.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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 [» ]
4BDT X-ray 3.10 B 1-61 [» ]
4EY8 X-ray 2.60 B 1-61 [» ]
ProteinModelPortali P0C1Z0.
SMRi P0C1Z0. Positions 1-61.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG006553.

Miscellaneous databases

EvolutionaryTracei P0C1Z0.

Family and domain databases

InterProi IPR003571. Snake_toxin.
IPR018354. Snake_toxin_BS.
[Graphical view ]
Pfami PF00087. Toxin_1. 1 hit.
[Graphical view ]
PROSITEi PS00272. SNAKE_TOXIN. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  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] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE, SUBCELLULAR LOCATION.
    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] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  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] [Europe PMC] [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. "Design, expression and characterization of mutants of fasciculin optimized for interaction with its target, acetylcholinesterase."
    Sharabi O., Peleg Y., Mashiach E., Vardy E., Ashani Y., Silman I., Sussman J.L., Shifman J.M.
    Protein Eng. Des. Sel. 22:641-648(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF THR-8; THR-9; ARG-11; HIS-29 AND LYS-32.
  5. "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] [Europe PMC] [Abstract]
    Cited for: PRELIMINARY CRYSTALLIZATION.
  6. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), DISULFIDE BONDS.
  7. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH ACHE, DISULFIDE BONDS.
  8. "Acetylcholinesterase inhibition by fasciculin: crystal structure of the complex."
    Bourne Y., Taylor P., Marchot P.
    Cell 83:503-512(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) IN COMPLEX WITH ACHE, DISULFIDE BONDS.
  9. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.76 ANGSTROMS) IN COMPLEX WITH ACHE, DISULFIDE BOND.
  10. "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] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), DISULFIDE BOND.
  11. "Structural evidence that human acetylcholinesterase inhibited by tabun ages through O-dealkylation."
    Carletti E., Colletier J.P., Dupeux F., Trovaslet M., Masson P., Nachon F.
    J. Med. Chem. 53:4002-4008(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH ACHE, DISULFIDE BOND.
  12. "Structures of human acetylcholinesterase in complex with pharmacologically important ligands."
    Cheung J., Rudolph M.J., Burshteyn F., Cassidy M.S., Gary E.N., Love J., Franklin M.C., Height J.J.
    J. Med. Chem. 55:10282-10286(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH ACHE, DISULFIDE BOND.
  13. "Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer's drugs targeting acetyl- and butyryl-cholinesterase."
    Nachon F., Carletti E., Ronco C., Trovaslet M., Nicolet Y., Jean L., Renard P.Y.
    Biochem. J. 453:393-399(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) IN COMPLEX WITH ACHE, DISULFIDE BOND.

Entry informationi

Entry namei3SE2_DENAN
AccessioniPrimary (citable) accession number: P0C1Z0
Secondary accession number(s): P01403
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: October 17, 2006
Last modified: January 7, 2015
This is version 41 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.