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P01391

- NXL1_NAJKA

UniProt

P01391 - NXL1_NAJKA

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
  1. 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

    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

    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

    IRCFITPDIT SKDCPNGHVC YTKTWCDAFC SIRGKRVDLG CAATCPTVKT   50
    GVDIQCCSTD NCNPFPTRKR P 71
    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 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