3L21_NAJOX
ID 3L21_NAJOX Reviewed; 73 AA.
AC P01382;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Alpha-elapitoxin-Nno2a;
DE Short=Alpha-EPTX-Nno2a;
DE AltName: Full=Long neurotoxin 1;
DE AltName: Full=Neurotoxin I;
DE Short=NT I {ECO:0000303|PubMed:26221036};
DE Short=Ntx-1;
DE Short=Toxin I {ECO:0000303|PubMed:9305882};
DE AltName: Full=NnoI {ECO:0000303|PubMed:9305882};
OS Naja oxiana (Central Asian cobra) (Oxus cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8657;
RN [1]
RP PROTEIN SEQUENCE, TOXIC DOSE, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=4411932; DOI=10.1016/0014-5793(74)80825-2;
RA Grishin E.V., Sukhikh A.P., Slobodyan L.N., Ovchinnikov Y.A., Sorokin V.M.;
RT "Amino acid sequence of neurotoxin I from Naja naja oxiana venom.";
RL FEBS Lett. 45:118-121(1974).
RN [2]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=9305882; DOI=10.1074/jbc.272.39.24279;
RA Servent D., Winckler-Dietrich V., Hu H.-Y., Kessler P., Drevet P.,
RA Bertrand D., Menez A.;
RT "Only snake curaremimetic toxins with a fifth disulfide bond have high
RT affinity for the neuronal alpha7 nicotinic receptor.";
RL J. Biol. Chem. 272:24279-24286(1997).
RN [3]
RP FUNCTION.
RX PubMed=26221036; DOI=10.1074/jbc.m115.648824;
RA Kudryavtsev D.S., Shelukhina I.V., Son L.V., Ojomoko L.O., Kryukova E.V.,
RA Lyukmanova E.N., Zhmak M.N., Dolgikh D.A., Ivanov I.A., Kasheverov I.E.,
RA Starkov V.G., Ramerstorfer J., Sieghart W., Tsetlin V.I., Utkin Y.N.;
RT "Neurotoxins from snake venoms and alpha-conotoxin ImI inhibit functionally
RT active ionotropic gamma-aminobutyric acid (GABA) receptors.";
RL J. Biol. Chem. 290:22747-22758(2015).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX PubMed=2387409; DOI=10.1016/0014-5793(90)81167-m;
RA Mikhailov A.M., Nickitencko A.V., Trakhanov S.D., Vainshtein B.K.,
RA Chetverina E.V.;
RT "Crystallization and preliminary X-ray diffraction study of neurotoxin-I
RT from Naja naja oxiana venom.";
RL FEBS Lett. 269:255-257(1990).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=8458425; DOI=10.1016/0014-5793(93)80073-4;
RA Nickitenko A.V., Michailov A.M., Betzel C., Wilson K.S.;
RT "Three-dimensional structure of neurotoxin-1 from Naja naja oxiana venom at
RT 1.9 A resolution.";
RL FEBS Lett. 320:111-117(1993).
RN [6]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=15606783; DOI=10.1111/j.1432-1033.2004.04465.x;
RA Talebzadeh-Farooji M., Amininasab M., Elmi M.M., Naderi-Manesh H.,
RA Sarbolouki M.N.;
RT "Solution structure of long neurotoxin NTX-1 from the venom of Naja naja
RT oxiana by 2D-NMR spectroscopy.";
RL Eur. J. Biochem. 271:4950-4957(2004).
CC -!- FUNCTION: Binds with high affinity to muscular (tested on Torpedo
CC marmorata AChR, Kd=0.38 nM) and neuronal (tested on chimeric alpha-
CC 7/CHRNA7, Kd=12 nM) nicotinic acetylcholine receptor (nAChR) and
CC inhibits acetylcholine from binding to the receptor, thereby impairing
CC neuromuscular and neuronal transmission (PubMed:9305882). The toxin
CC also shows a very weak inhibition of GABA(A) receptors composed of
CC alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits
CC (PubMed:26221036). {ECO:0000269|PubMed:26221036,
CC ECO:0000269|PubMed:9305882}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:4411932}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:9305882}.
CC -!- TOXIC DOSE: LD(50) is 0.56 mg/kg by intraperitoneal injection into
CC mice. {ECO:0000269|PubMed:4411932}.
CC -!- SIMILARITY: Belongs to the snake three-finger toxin family. Long-chain
CC subfamily. Type II alpha-neurotoxin sub-subfamily. {ECO:0000305}.
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DR PIR; A01653; N2NJ1R.
DR PDB; 1NTN; X-ray; 1.90 A; A=1-73.
DR PDB; 1W6B; NMR; -; A=1-73.
DR PDBsum; 1NTN; -.
DR PDBsum; 1W6B; -.
DR AlphaFoldDB; P01382; -.
DR BMRB; P01382; -.
DR SMR; P01382; -.
DR TCDB; 1.C.74.1.7; the snake cytotoxin (sct) family.
DR EvolutionaryTrace; P01382; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0099106; F:ion channel regulator activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR CDD; cd00206; snake_toxin; 1.
DR Gene3D; 2.10.60.10; -; 1.
DR InterPro; IPR003571; Snake_3FTx.
DR InterPro; IPR045860; Snake_toxin-like_sf.
DR InterPro; IPR018354; Snake_toxin_con_site.
DR InterPro; IPR035076; Toxin/TOLIP.
DR Pfam; PF00087; Toxin_TOLIP; 1.
DR SUPFAM; SSF57302; SSF57302; 1.
DR PROSITE; PS00272; SNAKE_TOXIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylcholine receptor inhibiting toxin;
KW Direct protein sequencing; Disulfide bond; Ion channel impairing toxin;
KW Neurotoxin; Postsynaptic neurotoxin; Secreted; Toxin.
FT CHAIN 1..73
FT /note="Alpha-elapitoxin-Nno2a"
FT /evidence="ECO:0000269|PubMed:4411932"
FT /id="PRO_0000093553"
FT DISULFID 3..22
FT /evidence="ECO:0000269|PubMed:15606783,
FT ECO:0000269|PubMed:8458425, ECO:0000312|PDB:1NTN,
FT ECO:0000312|PDB:1W6B"
FT DISULFID 15..43
FT /evidence="ECO:0000269|PubMed:15606783,
FT ECO:0000269|PubMed:8458425, ECO:0000312|PDB:1NTN,
FT ECO:0000312|PDB:1W6B"
FT DISULFID 28..32
FT /evidence="ECO:0000269|PubMed:15606783,
FT ECO:0000269|PubMed:8458425, ECO:0000312|PDB:1NTN,
FT ECO:0000312|PDB:1W6B"
FT DISULFID 47..58
FT /evidence="ECO:0000269|PubMed:15606783,
FT ECO:0000269|PubMed:8458425, ECO:0000312|PDB:1NTN,
FT ECO:0000312|PDB:1W6B"
FT DISULFID 59..64
FT /evidence="ECO:0000269|PubMed:15606783,
FT ECO:0000269|PubMed:8458425, ECO:0000312|PDB:1NTN,
FT ECO:0000312|PDB:1W6B"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:1NTN"
FT TURN 6..8
FT /evidence="ECO:0007829|PDB:1NTN"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:1NTN"
FT STRAND 21..27
FT /evidence="ECO:0007829|PDB:1NTN"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:1NTN"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:1NTN"
FT STRAND 54..59
FT /evidence="ECO:0007829|PDB:1NTN"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:1W6B"
SQ SEQUENCE 73 AA; 8031 MW; 0595C9F0AEDB8797 CRC64;
ITCYKTPIPI TSETCAPGQN LCYTKTWCDA WCGSRGKVIE LGCAATCPTV ESYQDIKCCS
TDDCNPHPKQ KRP
