ID   3L22_NAJME              Reviewed;          71 AA.
AC   P01388;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   25-MAY-2022, entry version 87.
DE   RecName: Full=Long neurotoxin 2;
DE   AltName: Full=Neurotoxin B {ECO:0000303|PubMed:4112538};
DE   AltName: Full=Tx-NM4 {ECO:0000303|PubMed:33672715};
OS   Naja melanoleuca (Forest cobra) (Black-lipped cobra).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX   NCBI_TaxID=8643;
RN   [1]
RP   PROTEIN SEQUENCE, AND SUBCELLULAR LOCATION.
RC   TISSUE=Venom;
RX   PubMed=4112538; DOI=10.1016/s0021-9258(19)45291-5;
RA   Botes D.P.;
RT   "Snake venom toxins. The amino acid sequences of toxins b and d from Naja
RT   melanoleuca venom.";
RL   J. Biol. Chem. 247:2866-2871(1972).
RN   [2]
RP   PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP   3D-STRUCTURE MODELING.
RC   TISSUE=Venom;
RX   PubMed=33672715; DOI=10.3390/toxins13020164;
RA   Son L., Kryukova E., Ziganshin R., Andreeva T., Kudryavtsev D.,
RA   Kasheverov I., Tsetlin V., Utkin Y.;
RT   "Novel three-finger neurotoxins from Naja melanoleuca cobra venom interact
RT   with GABAA and nicotinic acetylcholine receptors.";
RL   Toxins 13:0-0(2021).
CC   -!- FUNCTION: Binds with high affinity to muscular (alpha-1-beta-1-gamma-
CC       delta/CHRNA1-CHRNB1-CHRNG-CHRND) and neuronal (alpha-7/CHRNA7)
CC       nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine
CC       from binding to the receptor, thereby impairing neuromuscular and
CC       neuronal transmission (PubMed:33672715). Ranges of nAChR inhibition are
CC       in nanomolar (competitive binding with alpha-bungarotoxin gives Ki=2.17
CC       nM on muscle nAChR and Ki=26.9 nM on alpha-7) (PubMed:33672715). Also
CC       shows low inhibition on GABA(A) receptors (IC(50)~10 uM on all
CC       receptors tested: alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2), alpha-
CC       1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2), and alpha-3-beta-2-gamma-2
CC       (GABRA3-GABRB2-GABRG2)) (PubMed:33672715).
CC       {ECO:0000269|PubMed:33672715}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:33672715,
CC       ECO:0000269|PubMed:4112538}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000305|PubMed:33672715, ECO:0000305|PubMed:4112538}.
CC   -!- MASS SPECTROMETRY: Mass=7756.58; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:33672715};
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; A01659; N2NJ2W.
DR   AlphaFoldDB; P01388; -.
DR   SMR; P01388; -.
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   SUPFAM; SSF57302; SSF57302; 1.
DR   PROSITE; PS00272; SNAKE_TOXIN; 1.
PE   1: Evidence at protein level;
KW   Acetylcholine receptor inhibiting toxin; Direct protein sequencing;
KW   Disulfide bond; Ion channel impairing toxin; Neurotoxin;
KW   Postsynaptic neurotoxin; Secreted; Toxin.
FT   CHAIN           1..71
FT                   /note="Long neurotoxin 2"
FT                   /evidence="ECO:0000269|PubMed:33672715,
FT                   ECO:0000269|PubMed:4112538"
FT                   /id="PRO_0000093546"
FT   DISULFID        3..20
FT                   /evidence="ECO:0000250|UniProtKB:P25671"
FT   DISULFID        14..41
FT                   /evidence="ECO:0000250|UniProtKB:P25671"
FT   DISULFID        26..30
FT                   /evidence="ECO:0000250|UniProtKB:P25671"
FT   DISULFID        45..56
FT                   /evidence="ECO:0000250|UniProtKB:P25671"
FT   DISULFID        57..62
FT                   /evidence="ECO:0000250|UniProtKB:P25671"
SQ   SEQUENCE   71 AA;  7772 MW;  7F9B4B2FD2100AEF CRC64;
     IRCFITPDVT SQICADGHVC YTKTWCDNFC ASRGKRVDLG CAATCPTVKP GVNIKCCSTD
     NCNPFPTRNR P