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P01391

- NXL1_NAJKA

UniProt

P01391 - NXL1_NAJKA

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Protein

Alpha-elapitoxin-Nk2a

Gene
N/A
Organism
Naja kaouthia (Monocled cobra) (Naja siamensis)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.
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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei23 – 231Selectively binds to Torpedo AChR
Sitei25 – 251Binds to both neuronal and Torpedo AChRs
Sitei26 – 261Selectively binds to alpha-7 AChR
Sitei27 – 271Binds to both neuronal and Torpedo AChRs
Sitei28 – 281Selectively binds to alpha-7 AChR
Sitei29 – 291Binds to both neuronal and Torpedo AChRs
Sitei30 – 301Selectively binds to alpha-7 AChR
Sitei33 – 331Binds to both neuronal and Torpedo AChRs
Sitei35 – 351Selectively binds to alpha-7 AChR
Sitei36 – 361Binds to both neuronal and Torpedo AChRs
Sitei49 – 491Selectively binds to Torpedo AChR
Sitei65 – 651Binds to both neuronal and Torpedo AChRs

GO - Biological processi

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

Keywords - Molecular functioni

Acetylcholine receptor inhibiting toxin, Ion channel impairing toxin, Neurotoxin, Postsynaptic neurotoxin, Toxin

Names & Taxonomyi

Protein namesi
Recommended 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
OrganismiNaja kaouthia (Monocled cobra) (Naja siamensis)
Taxonomic identifieri8649 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaSerpentesColubroideaElapidaeElapinaeNaja

Subcellular locationi

GO - Cellular componenti

  1. other organism postsynaptic membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Toxic dosei

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 7171Alpha-elapitoxin-Nk2aPRO_0000093554Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi3 ↔ 20
Disulfide bondi14 ↔ 41
Disulfide bondi26 ↔ 30
Disulfide bondi45 ↔ 56
Disulfide bondi57 ↔ 62

Keywords - PTMi

Disulfide bond

Expressioni

Tissue specificityi

Expressed by the venom gland.

Interactioni

Subunit structurei

Monomer, homo- or heterodimer with cytotoxins 1, 2, and 3; disulfide-linked.7 Publications

Structurei

Secondary structure

1
71
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi6 – 105
Beta strandi19 – 257
Turni27 – 293
Helixi30 – 334
Beta strandi36 – 449
Beta strandi52 – 576
Beta strandi59 – 635

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliP01391.
SMRiP01391. Positions 1-71.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01391.

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.

P01391-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
IRCFITPDIT SKDCPNGHVC YTKTWCDAFC SIRGKRVDLG CAATCPTVKT
60 70
GVDIQCCSTD NCNPFPTRKR P
Length:71
Mass (Da):7,831
Last modified:July 21, 1986 - v1
Checksum:i6F07ADD885E9AC33
GO

Sequence databases

PIRiA01662. N2NJ1S.

Cross-referencesi

Sequence databases

PIRi A01662. N2NJ1S.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1CTX X-ray 2.80 A 1-71 [» ]
1LXG NMR - A 1-71 [» ]
1LXH NMR - A 1-71 [» ]
1YI5 X-ray 4.20 F/G/H/I/J 1-71 [» ]
4AEA X-ray 1.94 A/B 1-71 [» ]
ProteinModelPortali P01391.
SMRi P01391. Positions 1-71.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Phylogenomic databases

HOVERGENi HBG006553.

Miscellaneous databases

EvolutionaryTracei P01391.

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. "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. 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)

Entry informationi

Entry nameiNXL1_NAJKA
AccessioniPrimary (citable) accession number: P01391
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 1, 2014
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
Annotation programAnimal Toxin 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