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P01391 (NXL1_NAJKA) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-elapitoxin-Nk2a

Short name=Alpha-EPTX-Nk2a
Alternative name(s):
Alpha-cobratoxin
Short name=Alpha-CbT
Short name=Cbtx
Long neurotoxin 1
Neurotoxin 3
OrganismNaja kaouthia (Monocled cobra) (Naja siamensis)
Taxonomic identifier8649 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeElapinaeNaja

Protein attributes

Sequence length71 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The monomeric form binds with high affinity to muscular, Torpedo (muscle-type), and neuronal alpha-7 nicotinic acetylcholine receptors (nAChR). Has no effect on alpha-3/beta-2 nAChR. Causes paralysis by preventing acetylcholine binding to the nAChR. Does not show any blockade of the nicotine-evoked release of dopamine and does not affect ACh release. In mice lung cancer, causes reduction of tumor growth. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11

The homodimeric form binds with low affinity to Torpedo (muscle-type) and alpha-7 nAChRs, whereas it acquires the capacity to block alpha-3/beta-2 nAChRs. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11

Subunit structure

Monomer, homo- or heterodimer with cytotoxins 1, 2, and 3; disulfide-linked. Ref.2 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Subcellular location

Secreted.

Tissue specificity

Expressed by the venom gland.

Toxic dose

LD50 is 0.1 mg/kg by intravenous injection into mice.

Sequence similarities

Belongs to the snake three-finger toxin family. Type II alpha-neurotoxin subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 7171Alpha-elapitoxin-Nk2a
PRO_0000093554

Sites

Site231Selectively binds to Torpedo AChR
Site251Binds to both neuronal and Torpedo AChRs
Site261Selectively binds to alpha-7 AChR
Site271Binds to both neuronal and Torpedo AChRs
Site281Selectively binds to alpha-7 AChR
Site291Binds to both neuronal and Torpedo AChRs
Site301Selectively binds to alpha-7 AChR
Site331Binds to both neuronal and Torpedo AChRs
Site351Selectively binds to alpha-7 AChR
Site361Binds to both neuronal and Torpedo AChRs
Site491Selectively binds to Torpedo AChR
Site651Binds to both neuronal and Torpedo AChRs

Amino acid modifications

Disulfide bond3 ↔ 20 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Disulfide bond14 ↔ 41 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Disulfide bond26 ↔ 30 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Disulfide bond45 ↔ 56 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18
Disulfide bond57 ↔ 62 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Secondary structure

.............. 71
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01391 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 6F07ADD885E9AC33

FASTA717,831
        10         20         30         40         50         60 
IRCFITPDIT SKDCPNGHVC YTKTWCDAFC SIRGKRVDLG CAATCPTVKT GVDIQCCSTD 

        70 
NCNPFPTRKR P 

« Hide

References

[1]"Chemistry of some potent animal toxins."
Karlsson E.
Experientia 29:1319-1327(1973)
Cited for: PROTEIN SEQUENCE.
Tissue: Venom.
[2]"Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification."
Osipov A.V., Kasheverov I.E., Makarova Y.V., Starkov V.G., Vorontsova O.V., Ziganshin R.K., Andreeva T.V., Serebryakova M.V., Benoit A., Hogg R.C., Bertrand D., Tsetlin V.I., Utkin Y.N.
J. Biol. Chem. 283:14571-14580(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-17; 24-33 AND 36-68, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBUNIT.
Tissue: Venom.
[3]"Fluorescein isothiocyanate-labeled alpha-cobratoxin. Biochemical characterization and interaction with acetylcholine receptor from Electrophorus electricus."
Kang S., Maelicke A.
J. Biol. Chem. 255:7326-7332(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[4]"The sites of neurotoxicity in alpha-cobratoxin."
Martin B.M., Chibber B.A., Maelicke A.
J. Biol. Chem. 258:8714-8722(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[5]"Alpha-cobratoxin blocks the nicotinic acetylcholine receptor in rat hippocampal neurons."
Alkondon M., Albuquerque E.X.
Eur. J. Pharmacol. 191:505-506(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Alpha-bungarotoxin, kappa-bungarotoxin, alpha-cobratoxin and erabutoxin-b do not affect [3H]acetylcholine release from the rat isolated left hemidiaphragm."
Apel C., Ricny J., Wagner G., Wessler I.
Naunyn Schmiedebergs Arch. Pharmacol. 352:646-652(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor."
Servent D., Winckler-Dietrich V., Hu H.-Y., Kessler P., Drevet P., Bertrand D., Menez A.
J. Biol. Chem. 272:24279-24286(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Effects of alpha-erabutoxin, alpha-bungarotoxin, alpha-cobratoxin and fasciculin on the nicotine-evoked release of dopamine in the rat striatum in vivo."
Dajas-Bailador F., Costa G., Dajas F., Emmett S.
Neurochem. Int. 33:307-312(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Variability among the sites by which curaremimetic toxins bind to torpedo acetylcholine receptor, as revealed by identification of the functional residues of alpha-cobratoxin."
Antil S., Servent D., Menez A.
J. Biol. Chem. 274:34851-34858(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SYNTHESIS, MUTAGENESIS, SITES.
[10]"Molecular determinants by which a long chain toxin from snake venom interacts with the neuronal alpha 7-nicotinic acetylcholine receptor."
Antil-Delbeke S., Gaillard C., Tamiya T., Corringer P.-J., Changeux J.-P., Servent D., Menez A.
J. Biol. Chem. 275:29594-29601(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS, SITES.
[11]"Natural agents targeting the alpha7-nicotinic-receptor in NSCLC: a promising prospective in anti-cancer drug development."
Grozio A., Paleari L., Catassi A., Servent D., Cilli M., Piccardi F., Paganuzzi M., Cesario A., Granone P., Mourier G., Russo P.
Int. J. Cancer 122:1911-1915(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION ON TUMOR GROWTH.
[12]"Experimentally based model of a complex between a snake toxin and the alpha 7 nicotinic receptor."
Fruchart-Gaillard C., Gilquin B., Antil-Delbeke S., Le Novere N., Tamiya T., Corringer P.-J., Changeux J.-P., Menez A., Servent D.
Proc. Natl. Acad. Sci. U.S.A. 99:3216-3221(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[13]"Three-dimensional structure of the 'long' neurotoxin from cobra venom."
Walkinshaw M.D., Saenger W., Maelicke A.
Proc. Natl. Acad. Sci. U.S.A. 77:2400-2404(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), DISULFIDE BONDS.
[14]"The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4-A resolution."
Betzel C., Lange G., Pal G.P., Wilson K.S., Maelicke A., Saenger W.
J. Biol. Chem. 266:21530-21536(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), DISULFIDE BONDS.
[15]"Rapid determination and NMR assignments of antiparallel sheets and helices of a scorpion and a cobra toxin."
Laplante S.R., Mikou A., Robin M., Guittet E., Delsuc M.-A., Charpentier I., Lallemand J.-Y.
Int. J. Pept. Protein Res. 36:227-230(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
[16]"Alpha-cobratoxin: proton NMR assignments and solution structure."
le Goas R., Laplante S.R., Mikou A., Delsuc M.-A., Guittet E., Robin M., Charpentier I., Lallemand J.-Y.
Biochemistry 31:4867-4875(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
[17]"NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica."
Zeng H., Hawrot E.
J. Biol. Chem. 277:37439-37445(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
[18]"Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors."
Bourne Y., Talley T.T., Hansen S.B., Taylor P., Marchot P.
EMBO J. 24:1512-1522(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (4.2 ANGSTROMS), DISULFIDE BONDS.
[19]Erratum
Bourne Y., Talley T.T., Hansen S.B., Taylor P., Marchot P.
EMBO J. 25:266-266(2006)
+Additional computationally mapped references.

Cross-references

Sequence databases

PIRN2NJ1S. A01662.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CTXX-ray2.80A1-71[»]
1LXGNMR-A1-71[»]
1LXHNMR-A1-71[»]
1YI5X-ray4.20F/G/H/I/J1-71[»]
4AEAX-ray1.94A/B1-71[»]
ProteinModelPortalP01391.
SMRP01391. Positions 1-71.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

HOVERGENHBG006553.

Family and domain databases

InterProIPR003571. Snake_toxin.
IPR018354. Snake_toxin_BS.
[Graphical view]
PfamPF00087. Toxin_1. 1 hit.
[Graphical view]
PROSITEPS00272. SNAKE_TOXIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP01391.

Entry information

Entry nameNXL1_NAJKA
AccessionPrimary (citable) accession number: P01391
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programAnimal Toxin Annotation Program
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references